Synthetic studies on oligosaccharides composed of 5-thioglucopyranose units

Article abstract of DOI:10.1016/j.bmc.2005.05.028

Glycosylation reactions of 5-thioglucopyranosyl trichloroacetimidates bearing ethereal protective groups at the 2-O-position 14-15, and 37 proceed smoothly to give α-glycosides stereoselectively by using a catalytic amount of silyl triflate. This methodol

Full text of DOI:10.1016/j.bmc.2005.05.028

Bioorganic & Medicinal Chemistry 13 (2005) 5113–5144
Synthetic studies on oligosaccharides composed
of 5-thioglucopyranose units
Yasuharu Morii, Hiroko Matsuda,*,ꢀ Keiichiro Ohara, Masaru Hashimoto,*
Kazuo Miyairi and Toshikatsu Okuno
Faculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-Cho, Hirosaki, Aomori 036-8561, Japan
Received 29 January 2005;revised 17 May 2005;accepted 17 May 2005
Available online 27 June 2005
This article is dedicated to Professor Koji Nakanishi on his receipt of the Tetrahedron Prize.
Abstract—Glycosylation reactions of 5-thioglucopyranosyl trichloroacetimidates bearing ethereal protective groups at the 2-O-posi-
tion 14–15, and 37 proceed smoothly to give a-glycosides stereoselectively by using a catalytic amount of silyl triflate. This meth-
odology allowed us to achieve syntheses of sulfur-substituted isomaltotetraoside 2 and maltotetraoside 3. These studies also revealed
that benzoyl-protected 5-thioglucopyranosyl trichloroacetimidate 12 underwent b-selective glycosylation with C6-OH glucopyrano-
syl acceptors upon activation by BF3OEt2. This was applied for preparation of sulfur-substituted gentiobiosides 1 and 46.
ꢀ 2005 Elsevier Ltd. All rights reserved.
1. Introduction
have served well for our understanding of the mecha-
nism of exo-glycosidases in detail.
A number of carbohydrate analogues, the so-called
carbomimetics, have been developed as effective molecu-
lar probes for mechanistic investigations of glycosidases
as well as lead compounds in the search for pharmaceu-
tical drugs targeting, for example, digestive diseases.1,2
Most of them were designed3–6 as inhibitors against
exo-glycosidases, which cleave the terminal glycosidic
linkages in sugar chains. There also exists the other gly-
cosidase called endo-glycosidase, which hydrolyzes inter-
nal glycosidic linkages by recognizing only sequence
patterns of the carbohydrate units.6 In other words,
there are many cleavable glycosidic bonds, especially
within homo-polysaccharides such as amylose. Due to
the difficulty of designing suitable probes,4,7–10 mecha-
nistic studies for endo-glycosidases relatively lag behind,
whereas the character of exo-glycosidases has enabled
researchers to develop effective molecular probes, which
It is well known that the substrate for endo-glycosidases
is polysaccharide. For molecular design of an analogue
of oligosaccharide as an inhibitor against endo-glycosi-
dases, a desirable modification has to be replacement
of all enzymatically cleavable bonds with an inert func-
tionality. Even if individual changes are insignificant,
their accumulation may cause drastic structural changes.
Our solution for this problem was to use a sulfur atom
in place of the oxygen in a pyranose ring to raise the
resistance against the glycosidases with minimal struc-
tural changes, since the six-membered ring would absorb
these alterations. We anticipated that this methodology
is applicable for synthesis of molecular probes for the
endo-glycosidases.
Based on this concept, we investigated syntheses of
oligosaccharides composed of 5-thioglucopyranose
units.11–13 In the course of these studies, we succeeded
in developing a- and b-stereoselective glycosylation
reactions with 5-thioglucose derivatives. We have previ-
ously communicated the successful preparation of sul-
fur-substituted analogues of gentiobioside 1,13 and
isomaltotetraoside 2.14 We report, herein, the full details
of these studies as well as our successful synthesis of
maltotetraoside derivative 3.
Keywords: endo-Glycosidases; a-selective glycosylation; b-selective
glycosylation;5-Thioglucopyranosyl trichloroacetimidates.
*
Corresponding authors. Tel.: +81 172 39 3782;fax: +81 172 39 3782
(M.H.);tel.: +1 212 998 8463;fax: +1 212 260 7905 (H.M.);e-mail
addresses: hm722@nyu.edu, hmasaru@cc.hirosaki-u.ac.jp
ꢀ
Present address: Department of Chemistry, New York University,
100 Washington Square East, New York, NY 10003, USA.
0968-0896/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2005.05.028

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Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
Scheme 1. Preparation of 5-thioglucopyranosyl donors. Reagents and
conditions: (a) DBU, CCl3CN, CH2Cl2, 0 ꢁC, (11: 77%, 12: 85%, 13:
67%, 14: 78%, 15: 80%);(b) for 5a—DHP, cat. p-TsOH, CH2Cl2, 0 ꢁC,
95%, for 5b—EVE, cat. PPTS, CH2Cl2, 0 ꢁC, 96%;(c) NaOMe,
MeOH, rt, (6a: 82%, 6b: 86%);(d) for 7—BzCl, Py, rt, 94%;for 8—
PivCl, DMAP, Py, 75 ꢁC, 82%;for 9—NaH, BnBr, DMF, rt, 88%;for
10—NaH, MPMBr, DMF, rt, 95%;(e) from 7—p-TsOH, MeOH,
45 ꢁC, 85%;from 8—p-TsOH, MeOH, 72%;from 9—HClO4, MeOH,
rt, 90%, from 10: HCl, MeOH, rt, 81%.
2. Results and discussion
2.1. Development of effective and stereoselective glyco-
sylation reactions of 5-thioglucopyranosyl donors
and 96% yields, respectively). The EE ether 5b was used
for synthesis of isomaltotetraoside derivative 2 as de-
scribed later. The H NMR spectrum indicated that 5a
2.1.1. Preparation of glycosyl donors and acceptors.
There are many reports for preparing carbomimetics
composed of 5-thiopyranoses, in most of which
2,3,4,6-tetra-O-acetyl-5-thioglucopyranosyl trichloro-
acetimidate (11) was used as a glycosyl donor, probably
due to its synthetic feasibility.8,15–18 Both the stereo-
selectivity and the chemical yield of the glycosylation
of 11 depended on the acceptors employed. For exam-
ple, Mehta et al. performed the glycosylation reaction
in 80% yield, but with low selectivity (a:b = 1.5:1),16
while Izumi et al. obtained the a-disaccharide exclusive-
ly, but in only 22% yield.8 These results interestingly
suggest that the glycosylation of 11 has a tendency to
give a-glycosides stereoselectively in spite of its equato-
rial C2-acetoxy group,8,15–18 whereas this function usu-
ally results in b-selective glycosylation in regular
carbohydrate chemistry by the neighboring participa-
tion.19 It was indispensable for us to develop a general
and highly stereoselective glycosylation reaction of a 5-
thioglucopyranosyl donor for the synthesis of its oligo-
mers. We first prepared a series of glycosyl donors and
acceptors carrying a 5-thioglucopyranose unit in order
to investigate development of efficient glycosylation
reactions.
1
consisted of a mixture of two isomers. In both isomers,
the C1 protons (5.05 and 5.11 ppm) were determined to
be of equatorial orientation according to the observed
coupling constants (2.9 Hz), indicating that 5a consisted
of a diastereomeric mixture regarding the asymmetric
center of the THP group (50:50). After basic methanol-
ysis of 5a, the resultant tetraol 6a (82% yield) was con-
verted to the corresponding benzoates (!7, 94%
yield), pivaloates (!8, 82% yield), benzyl ethers (!9,
88% yield), and 4-methoxyphenylmethyl (MPM)21
ethers (!10, 95% yield) by following methods. After
the THP groups of 6–9 were selectively removed by acid-
ic treatment, the C1-OH groups were converted into the
corresponding trichloroacetimidates (!12–15) with tri-
chloroacetonitrile in the presence of a catalytic amount
of diazabicycloundec-7-ene (DBU).22 The 1H NMR
spectra of 11–15 suggested that all trichloroacetimidate
moieties possessed a-orientation. Chromatographic
purification of the imidates 11–15 had to be performed
quickly in order to minimize decomposition. Trichloro-
acetimidates 11–15 were all used for the next step imme-
diately. The use of other glycosyl donors, such as
glucosyl bromides or thioglucosides, seemed to be inap-
propriate as 5-thiopyranose donors because of intoler-
ance of its sulfide functionality under the activation
conditions with soft Lewis acids, such as AgOTf,23
HgBr2,24 or NIS-TfOH.25
As shown in Scheme 1, synthesis of 5-thioglucosyl do-
nors started with 2,3,4,6-tetra-O-acetyl-5-deoxy-5-thio-
D-glucopyranose 4, readily prepared from commercial
D-glucrono-6,3-lactone by following literature proce-
dure.20 Trichloroacetimidate 11 was obtained by an
established method.8 The preparation of 12–14 was per-
formed as follows. The anomeric hemithioacetal of 4
was protected as either THP (tetrahydropyranyl) or
EE (ethoxyethyl) ethers to provide 5a and 5b (95%
A series of glycosyl acceptors was prepared next. Accep-
tors with C6-OH 16a,26,27 16b,28 and C4-OH 1729 were
synthesized by established procedures. Acceptors with
a 5-thioglucopyranose framework 18 (C4-OH), 19 (C6-

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5115
2.1.2. Glycosylation reactions of 5-thioglucopyranosyl
donors bearing ester protective groups. With a series of
glycosyl donors and acceptors in hand, glycosylation
reactions of the 5-thioglucopyranosyl donors were inves-
tigated. We first examined the reactions with the acyl
protected 5-thioglucosyl donors, because it was antici-
pated that the ester groups would be removed readily
without affecting the sulfide functionality after glycosyl-
ation. Taking account of the steric factor, primary alco-
hols 16a, 16b, and 29 were first used as the acceptors for
the reactions.
OH), and 22 (C4-OH) were also synthesized as shown in
Scheme 2 in order to investigate the effects caused by the
sulfur atom in the acceptors. To the best of our knowl-
edge, the employment of 5-thioglucopyranose units as
glycosyl acceptors has been reported only in our earlier
communications.14,30
As we expected, upon activation with BF3OEt2 (0.5
equiv) glycosylation of acetyl protected trichloroacetim-
idate of regular glucopyranose 2331 with acceptor 16a
proceeded to give glycoside 24 in 76% yield with excel-
lent b-stereoselectivity (a:b > 5:95) (run 1 in Table 1).
However, when the corresponding 5-thio analogue 11
was subjected to this reaction, desired glycoside 25 was
obtained in low yield (19%) with lower b-selectivity
(a:b = 30:70, run 2). The use of triethylsilyl trifluo-
romethanesulfonate (TESOTf) as a promoter resulted
in giving glycoside 26 with unpredicted high a-stereo-
selectivity (a:b > 95:5, run 3) in only 10% yield. It was
found that when the reactions were activated by
BF3OEt2, benzoyl protected imidate 12 gave b-glyco-
sides 27–29 stereoselectively in good yields (runs 4–6).
In contrast, trimethylsilyl trifluoromethanesulfonate
(TMSOTf), TESOTf, and TfOH catalyzed the a-selec-
tive reactions to provide 27 and 29 (runs 7–9 and 11)
besides the unsatisfactory yields. Reaction using zinc
chloride did not provide glycoside 16a (run 10). Reaction
of imidate 13 bearing pivaloyl groups also gave b-glyco-
sides 30 and 31 in good yields in a highly b-stereoselective
manner by the use of BF3OEt2 (runs 12–13).
Benzoylation of 5-thioglucose under low temperature
gave acceptor 18 in one step, but this gave a mixture
at the anomeric position (a:b = 60:40). These isomers
were separated in preparative scale by medium pressure
column chromatography.
An acceptor with primary alcohol 19 was also prepared
from 5-thioglucose by C6-OH triphenylmethylation
(tritylation, Tr) and perbenzoylation of the remaining
hydroxyl groups, followed by selective removal of
the Tr group under acidic conditions. This procedure
gave an inseparable mixture with the b-anomer
(a:b = 83:17) besides which two extra steps required.
The following sequence allowed us to obtain diastereo-
merically pure 19 by using 6a: [(i) tert-butyldiphenylsilyl
(TBDPS) ether formation with the C6-OH, (ii) benzoy-
lation at the C2-, C3-, and C4-alcohols, (iii) acidic cleav-
age of the THP ether, (iv) benzoylation of the C1-OH,
and (v) removal of the TBDPS group]. The secondary
alcohol 22 was prepared from Driguezꢁs intermediate
20.20 Acetylation of 20 gave an anomeric mixture of
pentaacetate 21 (75:25, the stereochemistry was not as-
signed). Treatment with hydrazine acetate in N,N-di-
methylformamide (DMF) resulted in selective removal
of the C1-OAc and C5-SAc groups, which induced an
expansion of furanose into 5-thiopyranose framework.
The C1-OH was selectively acetylated to give diastereo-
merically pure 22 in 95% yield.
Reactions of donors 11 and 13 with the secondary alco-
hols 17 and 22 were not promising. Reaction of imidate
11 with C4-OH 22 gave a-glycoside 32 with high stereo-
selectivity (a:b > 95:5), but the yield was quite low
(<5%, run 14). The reaction with the acceptor 18, bear-
ing sterically hindered benzoyl groups, did not produce
desired glycoside 33 (run 15). A trace amount of a-gly-
coside 34, missing the C2-O-acetyl group, and acetate
35 were also isolated after repeated chromatographic
separations. In the case of 17, the reactions by using
BF3OEt2 gave no coupling product (runs 16 and 17),
but glycal 36 was detected (run 17). A similar pathway
leading to thioglycal formation has been reported by
Nishizawa and Yamada in their synthesis of
baiyunoside.32
Our results implied that the glycosylation reactions of
the acyl protected 5-thioglucopyranosyl donors proceed-
ed through the less reactive species than that corre-
sponding to regular glucopyranoses. This was
considered by molecular modeling calculations.33 In
order to simplify the discussion and save time for the
calculations, methyl glycosides Ia and Ib and cyclic acy-
loxonium intermediates IIa and IIb, bearing O-acetyl
groups only at the C2 position (gluco-type), were used
as model compounds (Table 2). Prior to ab initio calcu-
lations, a conformational search employing semi-empir-
Scheme 2. Preparation of 5-thioglucopyranosyl acceptors. Reagents
and conditions: (a) BzCl, Py, 40%, (b) (i) TrCl, DMAP, Py, 60 ꢁC, 75%,
(ii) BzCl, Py, 78%, (iii) p-TsOH, MeOH, 50 ꢁC, 81%, (c) (i) TBDPSCl,
ImH, 76%, (ii) BzCl, Py, 98%, (iii) HClO4, MeOH, 81%, (iv) BzCl, Py,
97%, (v) TBAF, AcOH, 92%, (d) Ac2O, Py, rt, quant, (e) (i) hydrazine
acetate, DMF, rt, 80%, (ii) AcCl, Py, DMAP, CH2Cl2, 0 ꢁC, 95%.

5116
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
Table 1. Glycosylation of ester protected 5-thioglucopyranosyl tri-
chloroacetimidates
Table 2. The C1–O bond length of cyclic carbenium ions and
glucosides estimated by MP2/6-31G*
Run Donors Acceptors Promoters Disaccharides
(yield a:b)
Other
products
0
˚
l (A)
˚
l (A)
Primary alcohol
1
2
23
11
11
12
12
12
12
12
12
12
12
13
13
16a
16a
19
BF3OEt2 24 (76%, >5:95)
BF3OEt2 25 (19%, 30:70)
X = O
X = S
1.406
1.410
À0.004
1.608
1.560
0.048
3
TESOTf
26 (10%, >95:5)
4
16a
16b
19
BF3OEt2 27 (77%, 17:83)
BF3OEt2 28 (82%, 15:85)
BF3OEt2 29 (62%, >5:95)
5
the C1 atom of IIb are bonded more tightly than those
of IIa. Because cleavage of this C–O bond must precede
the glycosylation reaction, the calculation results would
explain the reason why the ester protected 5-thiogluco-
pyranosyl donors were less reactive than the corre-
sponding regular glucopyranosyl donors, such as 23.
6
7
16a
16a
16a
16a
19
TESOTf 27 (38%, 84:16)
TMSOTf 27 (11%, >95:5)
8
9
TfOH
ZnCl2
TESOTf
27 (33%, 89:11)
No adduct
29 (38%, 84:16)
10
11
12
13
16a
16b
BF3OEt2 30 (69%, >5:95)
BF3OEt2 31 (86%, >5:95)
Since the b-glycosides were obtained stereoselectively
in practical yields by reaction with primary alcohols
using BF3OEt2 as a promoter (runs 2, 4, 6, 12, and
13 in Table 1), it would be evidence that the cyclic
oxocarbenium B was generated in the glycosylation
reaction (Scheme 3). On the other hand, by the use
of TESOTf for glycosylation of A, the corresponding
intermediate B would be formed, but it could be
much less reactive for b-glycosylation according to
the obtained elimination product such as glycal 36.
Secondary alcohol
14
15
11
11
22
18
TESOTf
TESOTf
32 (5%, >95:5)
33 (0%)
34, 35
(trace)
16
17
11
13
17
17
BF3OEt2 No adduct
BF3OEt2 No adduct
36 (trace)
Furthermore, the intermediate B also underwent
transformation into the intermediate D, likely
ical AM1 was performed for each model to provide ini-
tial geometries for the optimization. Then these were
further calculated employing MP2/6-31G* taking into
account the localized d orbital in the sulfur atom.
These calculations indicated that the length for the gly-
cosidic bonding (l, see Table 2) of Ib (X = S) is almost
identical to that of Ia (X = O). In contrast, the corre-
sponding bond length (l0) of cyclic thiocarbenium ion
(IIb, X = S) is ca. 3% shorter than the corresponding
C–O bonding of cyclic oxocarbenium ions (IIa,
X = O). It is suggested that the glycosidic oxygen and
Scheme 3.

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5117
through the orthoester C, to provide C2-deprotected
a-glycoside 34 and acylated acceptor 35. It was pro-
posed that the a-glycosides were derived from the
non-cyclic minor intermediate E (runs 3, 7, 8, 11,
and 14 in Table 1).
94% yield in a highly a-stereoselective manner. Donor
with MPM ethers 15 also gave a-glycosides 40–43
smoothly with various acceptors (runs 3–6). Both the
yields and stereoselectivities did not depend on the
acceptors in these reactions. The reaction with MOM
ether 37 was found to provide glycoside 44 in 79%
yield, but with lower stereoselectivity (a:b = 80:20).30
Presumably, the MOM group partially contributes to
the neighboring participation to generate the intermedi-
ate 45 which preferentially produced the b-glycoside.
Thus, we concluded that glycosylation using 5-thiog-
lucosyl trichloroacetimidates with Bn or MPM groups
is general and applicable for the synthesis of sulfur-
substituted oligosaccharides.
2.1.3. Glycosylation reactions of 5-thioglucopyranosyl
donors bearing ethereal protective groups. We next
investigated glycosylation of 5-thioglucopyranosyl do-
nors bearing ethereal protective groups instead of the
acyl protected donors. It was found that upon treat-
ment with a catalytic amount of TESOTf at À78 ꢁC,
glycosylation of 14 bearing benzyl ethers with acceptor
19 proceeded smoothly to provide a-glycoside 38 with
high stereoselectivity (a:b > 95:5) in 81% yield (run 1
in Table 3). The coupling constant for the C01-H signal
of this sample (2.9 Hz) in the 1H NMR spectrum,
showed that stereochemistry of the newly formed gly-
cosidic bond is of a-orientation. No signal correspond-
ing to the b-isomer was detected in the spectrum.
Glycosylation of donor 14 was also performed with
the secondary alcohol 22 to afford glycoside 39 in
2.1.4. Development of an effective deprotection reaction
of thiosaccharides. Removal of the protecting groups
from sulfur-containing saccharides was also studied.
Since cleavage for the acetates of the glycosides, such
as 25, was not determined due to the low yields of
the glycosylation, we first attempted deprotection of
27 and 28. Basic hydrolysis (NaOMe in MeOH) of
27 and 28 cleaved all the ester groups smoothly to give
sulfur-substituted methyl gentiobiosides 1 and its p-
nitrophenyl derivative 46 in high yields (Scheme 4).
However, basic methanolysis of pivaloate 30 was not
fruitful under similar conditions to provide only a
complex mixture.
Table 3. Glycosylation of 5-thioglucopyranosyl donors bearing
ethereal protective group
Run
Donors
Acceptors
Promoters
Disaccharides
(Yield, a:b)
Hydrogenolysis of 38 was performed with 20% Pd(OH)2
in MeOH. No reaction was observed at 1 atm H2 and
reaction at 5 atm of H2 gave many spots on the silica
gel TLC, probably due to partial deprotection. Extend-
ed reaction time did not promote further reaction. The
sluggishness of this reaction was most likely caused by
poisoning of catalyst with the sulfide. Deprotection of
the MPM masked disaccharides was attempted next.
Basic removal of the benzoyl groups of 41 was followed
by oxidative cleavage of MPM ethers with excess 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ) in aqueous
CH2Cl2 to give fully deprotected disaccharide 47 in
88% yield in two steps without affecting the sulfide func-
tion. Disaccharide 43 was subjected to the treatment
similar to that used for 41 to provide deprotected disac-
charide 48 in 77% yield. The negative-FABMS spectra
of 47 and 48 clearly showed pseudo-molecular ion sig-
nals both at m/z = 371 ([MÀH]À). It can be concluded
that DDQ treatment did not affect the oxidation-suscep-
tible sulfide function in thiosaccharides. On the other
hand, the following sequence for deprotection involved
a difficulty in purification. When DDQ treatment of 38
was performed prior to basic hydrolysis, the polarity
of the product was the same as that of a considerable
amount of hydroquinone (DDQH), the coproduct de-
1
2
3
4
5
6
7
14
14
15
15
15
15
37
19
22
TESOTf
TESOTf
TESOTf
TESOTf
TESOTf
TESOTf
TMSOTf
38 (81%, >95:5)
39 (94%, >95:5)
40 (94%, >95:5)
41 (82%, 88:12)
42 (60%, >95:5)
43 (87%, >95:5)
44 (79%, 80:20)30
19
16a
22
17
16a

5118
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
Scheme 4.
Scheme 5. Synthesis of thioisomaltotetraoside 2. Reagents and con-
ditions: (a) TrCl, DMAP, Py, rt, 80% (for 50a), 81% (for 51b);(b)
NaH, MPMBr, DMF, rt, 56% (for 51a), 62% (for 51b);(c) (from 51a)
p-TsOH, EtOH, rt, 50%, (from 51b) PPTS, EtOH, PrOH, rt, then
EtOH, 92% (see text);(d) CCl 3CN, DBU, CH2Cl2, rt, 82%;(e)
TESOTf, CH2Cl2, À78 ꢁC, 67% (for 54), 47% (for 56), 67% (67% for
58);(f) p-TsOH, MeOH, rt, 71% (for 55), 67% (for 57), (g) NaOMe,
MeOH, rt;(h) DDQ, aq CH 2Cl2, rt, 65% (2 steps).
rived from DDQ. Furthermore, DDQ treatment gave
only a complex mixture in which the 5-thioglucopyra-
nose unit must be of S,O-acetal form.
2.2. Synthesis of methyl thioisomaltotetraoside
We first applied these methodologies to the synthesis of
thioisomaltotetraoside 2. We planned to place a regular
methyl a-glucopyranoside unit at the reducing end, be-
cause endo-glycosidases were anticipated not to cleave
the glycosidic bond at the reducing terminus by consid-
ering its nature, and due to the synthetic feasibility. Fur-
thermore, this a-methyl glucoside moiety meets the
requirement at the DDQ oxidation stage of MPM ethers
(see Section 2.1.4). The use of the sole a-isomer would
simplify analysis of segments cleaved by glycosidases
(Scheme 5).
Otherwise, MPMBr-derived hydrogen bromide can
decompose the product during chromatographic purifi-
cation. Since acidic removal of the THP group was
accompanied by considerable cleavage of the Tr ether,
hemithioacetal 52 was obtained with a maximum yield
of 30%. Preparation of 53 through EE 51b was next
examined by using 6b as a starting material, to which
the sequence similar to that employed for the conversion
from 6a, was successfully applied. Ethoxyethyl ether 51b
was readily prepared from 6b. It was found that the EE
group of 51b was removed selectively in 92% yield by (i)
treatment with PPTS in a mixture of ethanol and 1-pro-
panol (3:1) at room temperature, (ii) concentration
directly in vacuo, and (iii) re-dilution with ethanol and
stirring at room temperature. Treatment of 51b with
PPTS in either methanol or ethanol alone was not
satisfactory because of poor solubility of 51b in these
solvents. Although 1-propanol dissolved 51b well, the
reaction was very slow at room temperature and
elevation of temperature declined the selectivity. The
hydroxyl group of 52 was smoothly converted into
We prepared trichloroacetimidate 53, a 5-thioglucose
donor with properly protected hydroxyl groups, which
would serve the further elongation of the thiosaccharide
chain at the C6 position. Selective tritylation of the C6
primary alcohol of 6a (!50a)34 was followed by the pro-
tection of all the remaining free hydroxyl groups as
MPM ethers with MPMBr/NaH (!51a).35,36 The excess
MPMBr had to be completely destroyed by MeOH/tri-
ethylamine prior to silica gel column chromatography.

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5119
trichloroacetimidate 53 in 82% yield under usual condi-
tions.22 Partial decomposition of imidate 53 took place
during silica gel column chromatography. Based on its
1H NMR spectrum, imidate 53 was obtained as a single
a-isomer.
As expected, upon treatment of 53 with a catalytic
amount of TESOTf in CH2Cl2, glycosylation with
acceptor 16a proceeded smoothly to give disaccharide
54 as an anomeric mixture (a54/b54, 67% and 7% yields,
respectively). These isomers were separated by prepara-
tive silica gel TLC. The stereochemistry of the major
isomer was confirmed as a-54 by observing a small cou-
1
pling constant for the C01-H (2.9 Hz) in the H NMR
Figure 1. Region of the FABMS spectrum of 2.
spectrum. On the other hand, the coupling constant
for the minor isomer was 8.3 Hz, suggesting b-glycoside
b-54. In order to prepare a stage for the next glycosyla-
tion, the Tr group of a-54 was selectively removed
by acidic treatment to liberate the free hydroxyl group
(a-54 ! 55, 71% yield). Glycosylation of 55 with donor
53 proceeded with high a-stereoselectivity to give trisac-
charide 56 in 47% yield. The corresponding b-isomer of
56 was not detected in this reaction. Trisaccharide 56,
thus prepared, was successfully converted into tetrasac-
charide 58 by repeating the sequence described above,
that is, cleavage of the Tr ether of 56 followed by glyco-
sylation of 57 with imidate 15 (56 ! 57, 71% yield,
57 ! 58, 67% yield, respectively). The third glycosyla-
tion proceeded with high stereoselectivity only to
provide a-glycoside 58 and the corresponding b-isomer
was not detected.
cleavage of 4,6-benzylidene acetal of saccharide is
known to proceed regioselectively by treatment with a
combination of reducing agent and acid.15,16 By taking
account of deprotection at the final stage of the synthe-
sis, MPM ether has an advantage over benzyl ether (see
Section 2.1.4);therefore, we also decided to use O-p-
methoxybenzylidene acetal for protection of the C4
and C6 positions.14–16 Treatment of 6a with anisalde-
hyde dimethyl acetal in the presence of camphorsulfonic
acid in DMF completed the selective acetal formation at
the C4 and C6 positions to give p-methoxybenzylidene
acetal 59 in 60% yield. The C2- and C3-OH functions
were then protected as MPM ethers (!60). It was found
that reductive cleavage of the acetal moiety in 60 pro-
ceeded regioselectively to give C4-OH 61 in 41% yield
by a combination of trimethylamine borane complex,
aluminum chloride37 and acid washed molecular sieves
4A.38 Due to the use of strong Lewis acid in this reac-
tion, undesired cleavage of the acid-labile THP ether
was not completely avoided to provide 1,4-diol 62
(28% yield). Interestingly, 61 was obtained as a single
isomer, although the starting material 60 was a
diastereomeric mixture with regard to the asymmetric
center of the THP group. Presumably, the THP ether
linkage of either isomer was selectively cleaved under
the reaction conditions. Both products 61 and 62, were
independently converted into the C1-OH 63. Acetyla-
tion of the C4-OH of 61 (97% yield) was followed
by acidic cleavage of the THP ether at the anomeric
position to give 63 in 71% yield. On the other hand,
diacetate derived from 62 was treated with hydrazine
acetate to undergo selective cleavage of the C1 acetate
to provide 63 in 81% yield in two steps. The anomeric
position was converted into trichloroacetimidate to
provide 64 as a single a-isomer in quantitative yield
(Scheme 6).
Based on our established protocol, deprotection of 58 by
a two-step sequence of basic methanolysis and DDQ
oxidation, gave the desired isomaltotetraoside 2 in
1
65% yield in two steps. The H NMR spectrum of 2 in
D2O displayed four anomeric signals with small cou-
pling constant (2.9–3.9 Hz), which assures that the
glycosylation reactions successfully proceeded with
a-stereoselectivity in each step. The 13C NMR spectrum
displayed 25 resonances, which further supports the
structural assignment. The negative FABMS spectrum
of 2 evidently displayed a pseudomolecular ion (m/z =
727, [MÀH]À) as well as several cluster ions. These were
assigned as adduct ions with chloride (m/z = 763:
[M+35Cl]À and 765: [M+37Cl]À), sodium (m/z = 749:
[M+NaÀ2H]À), and sodium chloride (m/z = 785:
[M+Na35ClÀH]À and 787: [M+Na37ClÀH]À) as shown
in Figure 1. However, signals due to sulfoxides
(m/z = 727 + 16 · n) and/or sulfones (m/z = 727 +
32 · n) were not detected. These results clearly proved
that oxidation of the sulfides in the 5-thiopyranose rings
did not occur throughout the synthesis.
2.3. Synthesis of methyl thiomaltotetraoside
As expected, the coupling reaction of 64 with acceptor
65 proceeded to give disaccharide 66 with a-stereoselec-
tivity (a:b = 90:10) in 79% yield by treatment with a cat-
alytic amount of TESOTf at À78 ꢁC. For analytical
purposes pure sample 66 was obtained by HPLC (the
major product: a-isomer: tR = 92 min, the minor prod-
uct: b-isomer: tR = 85 min, lBondasphere 150 SIL-100,
7.8 (/) · 300 mm, EtOAc/hexane 20:80, 4.0 mL/min
flow). In the preparative scale, the minor isomer of 66
1,4-a-Glycosyl linkage appears in the most common
polysaccharides in nature such as starch. With the suc-
cessful completion in preparation of methyl isomalto-
tetraoside 2, we next turned to investigation of the
synthesis of methyl maltotetraoside 3. Toward this
end, the C4 hydroxyl group of a 5-thioglucopyranose
donor has to be distinguished from all others. Reductive

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Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
Scheme 6. Synthesis of thiomaltotetraoside 3. Reagents and conditions: (a) anisaldehyde dimethyl acetal, CSA, DMF, 0 ꢁC, 60%;(b) NaH, MPMBr,
DMF, rt, 100%;(c) BH 3NMe3, AlCl3, MSAW300, THF, À15 ꢁC, 41% (61), 28% (62);(d) (i) Ac 2O, Py, rt, 97%, (ii) p-TsOH, MeOH-THF, rt, 71%;
(e) (i) Ac2O, Py, rt, 100%, (ii) hydrazine acetate, DMF, rt, 81%;(f) CCl 3CN, DBU, CH2Cl2, 0 ꢁC, 100%;(g) TESOTf, MS4A, CH 2Cl2, À78 ꢁC, 79%;
(h) NaOMe, MeOH-THF, 50 ꢁC, 98%;(i) TESOTf, MS4A, CH 2Cl2, À78 ꢁC, 76%;(j) NaOMe, MeOH-THF, 50 ꢁC, 75%;(k) TESOTf, MS4A,
CH2Cl2, À78 ꢁC, 68%;(l) NaOMe, MeOH-THF, 50 ꢁC, 76%;(m) DDQ, aq CH 2Cl2, 88%.
was separated at the later synthetic stage. Basic hydroly-
sis of the acetyl group of 66 gave acceptor 67 in 89%
yield. Glycosylation of a diastereomeric mixture 67 with
donor 64 under the same conditions described above
gave a mixture of four possible isomers of trisaccharides
containing 68 as a major isomer in 79% yield. HPLC
purification allowed us to remove only two minor iso-
mers. Fortunately, removal of the last minor isomer
was made after conversion into alcohol 69. The stereo-
selectivity of the second glycosylation step was estimated
to be a:b = 84:16 by performing the reaction using dia-
stereomerically pure 67, prepared from the HPLC puri-
fied sample 66. The third glycosylation giving a tetramer
was performed. As expected, the reaction proceeded
with a-stereoselectivity (a:b = 90:10) to give 70 in 68%
yield. Removal of the minor isomer was made by pre-
parative silica gel TLC after cleavage of the acetate
(!71). Although glycosylation of 15 gave the corre-
sponding tetrasaccharide with high a-stereoselectivity,
all attempts at separation of these diastereomers resulted
in failure.
3. Conclusion
We demonstrated that MPM-protected 5-thioglucopyr-
anosyl trichloroacetimidates are generally applicable
for a-stereoselective glycosylations promoted by
TESOTf. Cleavage of MPM ethers of saccharides com-
posed of 5-thioglucopyranose units proceeded smoothly
to provide fully deprotected sulfur-substituted saccha-
ride analogues by using DDQ without any loss of the
sulfide functions. Based on the methodologies, we
achieved the syntheses of sulfur-substituted analogues
isomaltotetraoside 2 and maltotetraoside 3. Benzoyl-
protected 5-thioglucopyranosyl trichloroacetimidate
underwent stereoselective b-glycosylation with C6-OH
glucopyranosyl acceptors upon activation by BF3OEt2.
We also achieved synthesis of sulfur-substituted gentio-
biosides 1 and 46.
However, we could not detect analogues 1–3 on a small
scale by UV-detection on HPLC due to the absence of
chromophores, which did not allow us to examine resis-
tance against amylase using them. The p-nitrophenyl
gentiobioside 46 was only applicable for the analysis
determining that it was not hydrolyzed by b-glycosi-
dases from almond or scallop shell, although p-nitro-
phenyl glycoside of regular gentiobioside 72 was
hydrolyzed smoothly under the same conditions. In or-
der to investigate enzymatic properties, chromophores
must be introduced into these analogues. We are now
intending to introduce a p-nitrophenyl group to the
reducing terminus of 1–3. Although we have succeeded
in developing the basic methodology for the synthesis
Finally, all MPM ethers of 71 were cleaved according to
the protocol developed in our model studies. Treating 71
with excess DDQ in aqueous CH2Cl2 gave a single spot
on the silica gel TLC. After washing the mixture with
EtOAc, the resulting aqueous solution was passed
through a SepPak ODSꢂ to give pure maltoside ana-
logue 3 in 88% yield, whose structure was confirmed in
the same manner as described for isomaltotetraoside
analogue 2. All the data obtained supported the struc-
tural assignment.

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5121
of oligosaccharides composed of 5-thiopyranoses, some
modifications may be required for these schemes be-
cause p-nitrophenyl glycoside is much less stable than
methyl glycoside, especially under acidic conditions.
These syntheses are in progress in our laboratories.
for aqueous conditions or reduction with H2. Dichloro-
methane and tetrahydrofuran were freshly distilled from
calcium hydride and benzophenone-ketyl, respectively.
Molecular sieves were finely powdered and activated
(200 ꢁC in vacuo) before use. Conversion of C1-OH 5-
thioglucopyranose into the corresponding trichloro-ace-
timidate was performed as follows (general procedure A),
which is similar to Izumiꢁs report;8 a solution of C1-OH
5-thioglucopyranose in CH2Cl2 was stirred with
CCl3CN in the presence of a catalytic amount of DBU
at 0 ꢁC for 1 h. The mixture was diluted with benzene
and the volatiles were removed in vacuo. Purification
of the residue by silica gel chromatography gave the cor-
responding trichloroacetimidate. Glycosylation reac-
tions were performed as follows (general procedure B);
a mixture of donor and acceptor was stirred with freshly
activated powdered molecular sieves in CH2Cl2 at room
temperature for 1 h under Ar atmosphere. A catalytic
amount of promoter (0.05 equiv) was then added into
the suspension at À78 ꢁC. After stirring for an addition-
al 2 hr at the same temperature, the reaction was
allowed to warm to room temperature over an addition-
al 1 h. Pyridine was added at À78 ꢁC and the resultant
mixture was passed through silica gel pad, and then con-
centrated in vacuo. Purification by silica gel column
chromatography gave glycosides.
4. Experimental
4.1. General methods
Melting points were determined with a Yanako MP-J3
micro melting point apparatus and were uncorrected.
Optical rotations were measured on a HORIBA
SEPA300 high-sensitivity polarimeter. For compounds,
consisting of a mixture of diastereomers, the optical
rotations were not measured. 1H NMR spectra were
measured on a JEOL ALPHA 400 spectrometer
(400 MHz). The chemical shifts are expressed in ppm
downfield from the signal of tetramethylsilane used as
an internal standard in the case of employing CDCl3.
When other solvents were employed, the residual proton
signals in deuteriosolvents C6HD5 (7.15 ppm),
CHD2OD (3.30 ppm), or HDO (4.63 ppm) were used
as the internal standards. Splitting patterns are designat-
ed as s (singlet), d (doublet), t (triplet), q (quartet), m
(multiplet), and br (broad). 13C NMR spectra were
4.2. Tetrahydropyranyl 2,3,4,6-tetra-O-acetyl-5-deoxy-5-
thio-a-D-glucopyranoside (5a)
A solution of 2,3,4,6-O-acetyl-5-deoxy-5-thioglucopyra-
nose 4 (8.03 g, 22.0 mmol) in CH2Cl2 (250 mL) was
stirred with 2,3-dihydropyran (2.4 mL, 26.4 mmol) and
p-TsOH (10.0 mg, 52.6 lmol) at 0 ꢁC. After stirring for
1.5 h, the mixture was neutralized with Et3N (30.0 lL),
and then concentrated in vacuo. Purification of the
residue by silica gel column chromatography (EtOAc/
hexane 35:65) afforded 5a (9.39 g, 20.9 mmol, 95%) as
a syrup. The 1H NMR spectrum of this sample indicated
the sample consists of a mixture of diastereomers due to
the asymmetric center of the THP group (50:50). IR
(film) 2950, 1750, 1375, 1225, 1120, 1070, 1020,
965 cmÀ1. 1H NMR (CDCl3, Signals assignable are only
described.) d 1.25–1.90 (6H, C30H2, C40H2, C50H2),
2.020, 2.027, 2.034, 2.038, 2.045, 2.050, 2.065, 2.071
(each 3H · 0.5, s, each CH3CO), 3.44 (1H · 0.5, ddd,
J = 3.4, 4.4, 10.7 Hz, C5H), 3.51–3.62 (1H, m, C6HH),
3.67 (1H · 0.5, ddd, J = 3.4, 4.4, 11.2 Hz, C5H), 3.96
(1H, m, C6HH), 4.03 (1H · 0.5, dd, J = 3.4, 12.2 Hz,
C6H), 4.09 (1H · 0.5, dd, J = 3.4, 12.2 Hz, C6H), 4.39
(1H · 0.5, dd, J = 4.4, 12.2 Hz, C6H), 4.41 (1H · 0.5,
dd, J = 4.4, 12.2 Hz, C6H), 5.05 (1H · 0.5, d,
J = 2.9 Hz, C1H), 5.11 (1H · 0.5, d, J = 2.9 Hz, C1H),
5.17 (1H · 0.5, dd, J = 2.9, 10.2 Hz, C2H), 5.26
(1H · 0.5, dd, J = 2.9, 10.2 Hz, C2H), 5.31 (1H · 0.5,
dd, J = 9.2, 11.2 Hz, C4H), 5.33 (1H · 0.5, dd, J = 9.2,
10.7 Hz, C4H), 5.51 (1H · 0.5, dd, J = 9.2, 10.2 Hz,
C3H), 5.55 (1H · 0.5, dd, J = 9.2, 10.2 Hz, C3H). EI-
MS (%, rel int) m/z 388 (0.58, [MÀCH3COOH]+), 347
(1.5, [MÀTHPO]+), 328 (2.4, [MÀ(2 · CH3COOH)]+),
227 (4.3, [MÀ(2 · CH3COOH)-THPO]+), 184 (14,
recorded on
a JEOL ALPHA 400 spectrometer
(100 MHz). The isotopes 13C in the solvents were used
as the internal standard (13CDCl3 77.0 ppm, 13C6D6
128.0 ppm, or 13CD3OD 49.5 ppm). For 13C NMR spec-
tra measured in D2O, default offset was employed and
correction was not performed. Assignments of the
signals are in accordance with the numbering based on
IUPAC nomenclature. For carbohydrate derivatives,
numbering is based on carbohydrate nomenclature. IR
spectra were obtained with HORIBA FT-720 Fourier
transform infrared spectrometer on a KBr cell. Mea-
surements of electron ionization, field desorption, fast
atom bombardment, or electrospray ionization mass
spectra (EI-MS, FD-MS, FAB-MS, or ESI-MS, respec-
tively) were performed on a JEOL JMS AX500 spec-
trometer or a JEOL JMS AX102A spectrometer at
Hokkaido University. When MS spectra were measured
by negative mode, ꢂnegative modeꢁ is indicated. Unstable
compounds such as glycosyl imidates could not be sub-
jected to MS analysis. Analytical and preparative thin-
layer chromatographies were carried out using pre-coat-
ed silica gel plates, Merck silica gel 60 F254. Silica gel
used for column chromatography was Merck silica gel
60 or Wako gel C200. All reactions were carried out un-
der N2 or Ar atmosphere using dried solvents excepted
[MÀ(2 · CH3COOH)-THPO-CH3CO]+),
85
(100,
THP+). FD-MS (%, rel int) 448 (11, M+), 85 (100,

5122
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
C5H9O+). EI-HRMS Found m/z = 388.1178. Calcd for
C17H24O8S: [MÀCH3COOH]+, 388.1192.
4.5. Ethoxyethyl 5-deoxy-5-thio-a-D-glucopyranoside (6b)
A solution of 5b (229 mg, 525 lmol) in MeOH (7.0 mL)
was stirred with NaOMe (142 mg, 2.63 mmol) at room
temperature for 20 min. After the mixture was concen-
trated in vacuo, the residue was dissolved in H2O and
was passed through Amberlite IRC-50 column (H+
form). The eluent was concentrated in vacuo. Purifica-
tion of the residue by silica gel column chromatography
(acetone/CH2Cl2 60:40) afforded 6b (122 mg, 452 lmol,
86%) as a colorless syrup. The 1H NMR spectra indicat-
ed that the sample consists of a mixture of diastereomers
due to the asymmetric center in the EE group (50:50). IR
4.3. 1-Ethoxyethyl 2,3,4,6-tetra-O-acetyl-5-deoxy-5-thio-
a-D-glucopyranoside (5b)
A solution of 4 (200 mg, 549 lmol) in CH2Cl2 (5.0 mL)
was stirred with ethyl vinyl ether (200 lL, 659 lmol) in
the presence of PPTS (10.4 mg, 54.9 lmol) at room tem-
perature. After stirring for 10 h, the mixture was neu-
tralized with Et3N, and concentrated under reduced
pressure. Purification of the residue by silica gel column
chromatography (EtOAc/hexane 35:65) afforded 5b
1
1
(229 mg, 525 lmol, 96%) as a colorless syrup. The H
(film) 3400, 2980, 2930, 1340, 1070, 1025, 950 cmÀ1. H
NMR spectra indicated that the sample consists of a
mixture of diastereomers due to the asymmetric center
in the EE group (50:50). IR (film) 2985, 1750, 1380,
NMR (D2O) d 1.07 (3H · 0.5, t, J = 7.3 Hz, CH3CH2O),
1.08 (3H · 0.5, t, J = 6.8 Hz, CH3CH2O), 2.94
(1H · 0.5, dt, J = 4.4, 9.8 Hz, C5H), 3.02 (1H · 0.5, dt,
J = 4.4, 9.3 Hz, C5H), 4.67 (1H · 0.5, d, J = 3.4 Hz,
C1H) 5.07 (1H · 0.5, q, J = 5.3 Hz, EtO(Me)CH). EI-
MS (%, rel int) 268 (trace, M+), 253 (trace, [MÀCH3]+),
250 (0.3, [MÀH2O]+), 222 (6, [MÀEtOH]+), 73 (100,
[CH3CH2O = CHCH3]+). FD-MS (%, rel int) 268 (100,
M+). EI-HRMS Found m/z = 250.0846. Calcd for
C10H18O5S: [MÀH2O]+, 250.0875.
1
1225, 1140, 1040, 960 cmÀ1. H NMR (C6D6) d: 0.99,
1.05 (each 3H · 0.5, t, J = 7.6 Hz, CH3CH2O(CH3)CH),
1.11, 1.17 (each 3H · 0.5, d, J = 5, 4 Hz, CH3CH2O
(CH3)CH), 1.61, 1.65, 1.689, 1.691, 1.695, 1.679, 1.679,
1.703 (each 3H · 0.5, s, CH3CO), 3.17–3.35 (2H ·
0.5 + 1H · 0.5, CH3CH2O(CH3)CH), 3.66 (1H · 0.5,
CH3CH2O(CH3)CH), 3.42, 3.56 (each 1H · 0.5, m,
C5H), 3.92–3.98, 4.38–4.44 (each 2H · 0.5, C6H2),
4.49, 4.79 (each 1H · 0.5, s, CH3CH2O(CH3)CH),
4.68, 5.09 (each 1H · 0.5, d, C1H), 5.29, 5.36 (each
1H · 0.5, dd, C2H), 5.54–5.60 (1H, C3H), 5.82–5.90
(1H · 0.5, C4H). EI-MS (%, rel int) 376 (3,
[MÀCH3COOH]+), 347 (9, [MÀEEO]+), 73 (100,
[CH3CH2O@CHCH3]+). FD-MS (%, rel int) 436 (16,
M+). EI-HRMS Found m/z = 376.1195. Calcd for
C16H24O8S: [MÀCH3COOH]+, 376.1192.
4.6. Tetrahydropyranyl 2,3,4,6-tetra-O-benzoyl-5-deoxy-
5-thio-a-D-glucopyranoside (7)
A solution of 6a (121 mg, 430 lmol) in pyridine (4.0 mL)
was stirred with benzoyl chloride (300 lL, 2.58 mmol) at
room temperature for 1 h. After MeOH (500 lL) was
added to decompose the excess reagent, the volatiles were
removed in vacuo. The residue was dissolved in EtOAc
and the resulting solution was washed with H2O. The
aqueous layer was extracted with EtOAc ( · 3). The ex-
tracts were combined, washed with brine, dried over
MgSO4, and concentrated in vacuo. Purification of the
residue by silica gel chromatography (EtOAc/hexane
10:90) gave 7 (281 mg, 404 lmol, 94%) as a syrup. This
sample consisted of the two diastereomers due to the
asymmetric center in the THP group (50:50). IR (film)
2930, 2855, 1730, 1450, 1270, 1105, 1070, 1025, 710,
4.4. Tetrahydropyranyl 5-deoxy-5-thio-a-D-glucopyrano-
side (6a)
A solution of 5a (9.38 g, 20.9 mmol) in MeOH
(300 mL) was stirred with NaOMe (5.65 g, 105 mmol)
at room temperature. After stirring for 3.5 h, DOWEX
50W (H+ form) was added until the solution was neu-
tralized. The mixture was filtered and the filtrate was
concentrated in vacuo. Purification of the residue by
silica gel column chromatography (acetone–CH2Cl2
70:30) afforded 6a (4.8 g, 17.1 mmol, 82%) as a syrup.
1
680 cmÀ1. H NMR (CDCl3) d 1.20–2.05 (6H, C30H2,
C40H2, C50H2), 3.26, 3.59 (each 1H · 0.5 br d,
J = 11.7 Hz, C60HH), 3.59, 4.05 (each 1H · 0.5 br d,
J = 11.7 Hz, C60HH), 3.85, 4.09 (each 1H · 0.5, ddd,
J = 3.9, 4.4, 9.8 Hz, C5H), 4.563, 4.565 (each 1H · 0.5,
dd, J = 4.4, 12.2 Hz, C6HH), 4.61, 4.67 (each 1H · 0.5,
dd, J = 3.9, 12.2 Hz, C6HH), 4.85, 5.23 (each 1H · 0.5,
br, C20H), 5.30, 5.41 (each 1H · 0.5, d, J = 3.4 Hz,
C1H), 5.62, 5.73 (each 1H · 0.5, dd, J = 3.4, 9.8, C2H),
5.95, 5.97 (each 1H · 0.5, t, J = 9.8 Hz, C4H), 6.20,
6.24 (each 1H · 0.5, t, J = 9.8 Hz, C3H), 7.15–7.15
(20H, aromatic protons). FD-MS (%, rel int) 696 (2.9,
[M+H]+), 695 (3.4, M+), 611 (29, [MÀTHP]+), 85 (100,
THP+). FD-HRMS Found m/z = 696.2047. Calcd for
C39H36O10S: M+, 696.2029.
1
The H NMR spectra indicated that the sample con-
sists of a mixture of diastereomers due to the asymmet-
ric center in the THP group (50:50). IR (film) 3380,
2940, 1120, 1070, 1025, 975, 755 cmÀ1
.
1H NMR
(D2O, Signals assignable are only described.) d 1.20–
1.80 (6H, C30H2, C40H2, C50H2), 2.93 (1H · 0.5, ddd,
J = 3.4, 5.4, 9.8 Hz, C5H), 3.11 (1H · 0.5, ddd,
J = 3.4, 5.4, 9.8 Hz, C5H), 3.57 (1H · 0.5, t,
J = 8.8 Hz, C3H), 3.60 (1H · 0.5, t, J = 9.3 Hz, C3H),
3.68 (1H · 0.5, dd, J = 2.9, 9.3 Hz, C2H), 3.82
(1H · 0.5, dd, J = 5.4, 11.8 Hz, C6H), 4.77 (1H · 0.5,
d, J = 2.9 Hz, C1H), 4.87 (1H · 0.5, d, J = 3.4 Hz,
C1H), 4.83, 5.07 (each 1H · 0.5, br, C010H). EI-MS
(%, rel int) 280 (0.76, M+), 262 (1.0, [MÀH2O]+), 244
(trace, [MÀ(2 · H2O)]+), 196 (8.1, [MÀDHP]+), 178
(6.4, [MÀTHPOH]+), 85 (100, THP+). FD-MS (%, rel
int) 280 (79, M+), 85 (100, THP+). EI-HRMS Found
m/z = 280.0957. Calcd for C11H20O6S: M+, 280.0981.
4.7. Tetrahydropyranyl 2,3,4,6-tetra-O-pivaloyl-5-deoxy-
5-thio-a-D-glucopyranoside (8)
A solution of 6a (127 mg, 453 lmol) and DMAP
(250 mg, 2.06 mmol) in pyridine (46.0 mL) was stirred

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5123
with PivCl (558 lL, 4.53 mmol) at 75 ꢁC for 30 h. After
MeOH (500 lL) was added to decompose the excess re-
agent, the volatiles were removed in vacuo. The residue
was dissolved in EtOAc and washed with H2O. The
aqueous layer was extracted with EtOAc (·3). The ex-
tracts were combined, washed with brine dried over
MgSO4, and concentrated in vacuo. Purification of the
residue by silica gel chromatography (EtOAc/hexane
5:95) gave 8 (228 mg, 371 lmol, 82%) as a syrup. The
1H NMR spectrum indicated that this sample consisted
of the two diastereomers due to the asymmetric center
in the THP group (50:50). IR (film) 2970, 1740, 1480,
manner similar to that described for 9. After stirring
for 1 hr at room temperature, the excess reagents were
decomposed by the addition of MeOH (ca. 1.0 mL)
and Et3N (ca. 1.0 mL). After stirring for additional
30 min, the mixture was poured into water and the
resulted solution was extracted with EtOAc (·3). The
combined extracts were washed with brine, dried over
MgSO4, and concentrated in vacuo. The residue was dis-
solved in pyridine (3.0 mL), and the solution was stirred
with Ac2O (1.0 mL) at room temperature for 1 hr in or-
der to convert the generated MPMOH into the corre-
sponding acetate. After concentration in vacuo,
purification of the residue by silica gel column chromat-
ography (EtOAc/hexane = 25:75) afforded 10 (676 mg,
889 lmol, 95%) as a colorless syrup. The 1H NMR spec-
trum indicated that this sample consists of the two dia-
stereomers due to the asymmetric center in the THP
group (50:50). IR (film) 2920, 2850, 1610, 1511, 1245,
1095, 1070, 135, 820 cmÀ1. 1H NMR (CDCl3, Some sig-
nals could not be assigned due to signals overlapping) d:
1.40–1.87 (6H, C30H2, C40H2, C50H2), 3.18 (1H · 0.5,
ddd, J = 2.5, 3.9, 10.3 Hz, C5H), 3.41 (1H · 0.5, ddd,
J = 2.4, 3.4, 10.2 Hz, C5H), 3.48–3.58 (4H · 0.5,
C6HH, C60HH), 3.749, 3.754, 3.771, 3.774, 3.781,
3.781, 3.784, 3.789 (each 3H · 0.5, s, CH3O), 3.73–3.97
(8H · 0.5, C2H, C3H, C4H, C6HH), 4.01, 4.05 (each,
1H · 0.5, br d, J = 9.8 Hz, C60HH), 4.40–4.50
(6H · 0.5, ArCH2O), 4.57–4.92 (10H · 0.5, ArCH2O),
4.85 (1H · 0.5, d, J = 3.0 Hz, C1H), 5.03 (1H · 0.5, d,
J = 2.9 Hz, C1H), 4.97, 5.07 (each 1H · 0.5, C01H),
6.79–7.34 (16H, aromatic protons). FD-MS (%, rel int)
760 (6.0, M+), 640 (82, [M+H-MPM]+), 639 (100,
[MÀMPM]+). FD-HRMS Found m/z = 640.2860. Calcd
for C39H44O6S: [M+H-MPM]+, 640.2859.
1
1395, 1365, 1280 cmÀ1. H NMR (CDCl3) d 1.10, 1.11,
1.12, 1.146, 1.146, 1.152, 1.180, 1.85 (each 9H · 0.5, s,
(CH3)3CCO), 1.45–1.88 (6H, C30 it H2, C40H2, C50H2),
3.36, 3.64 (each 1H · 0.5, ddd, J = 2.9, 5.4, 10.7 Hz,
C5H), 3.46, 3.55 (each 1H · 0.5, br dt, J = 4.4, 11.7 Hz,
C60HH), 3.74, 3.95 (each 1H · 0.5, ddd, J = 3.4, 8,3,
11.7 Hz, C60HH), 4.09, 4.13 (each 1H · 0.5, J = 5.4,
12.2 Hz, C6HH), 4.18, 4.19 (each 1H · 0.5, dd, J = 2.9,
12.2 Hz, C6HH), 4.77, 5.00 (each 1H · 0.5, br, C20H),
4.95, 5.52 (each 1H · 0.5, d, J = 2.9 Hz, C1H), 5.11,
5.21 (each 1H · 0.5, dd, J = 2.9, 9.8 Hz, C2H), 5.346,
5.351 (each 1H · 0.5, dd, J = 9.8, 10.7 Hz, C4H), 5.55,
5.58 (each 1H · 0.5, t, J = 9.8 Hz, C3H). FD-MS (%,
rel int) 617 (6.8, [M+H]+) 616 (25, M+), 532 (15,
[M+HÀPiv]+), 531 (47, [MÀPiv]+), 85 (100, Piv+), 57
(52, (CH3)3C+). FD-HRMS Found m/z = 616.3260.
Calcd for C31H52O10S: M+, 616.3281.
4.8. Tetrahydropyranyl 2,3,4,6-tetra-O-benzyl-5-deoxy-5-
thio-a-D-glucopyranoside (9)
To a suspension of 6a (62.0 mg, 221 lmol) and NaH
(freshly washed with hexane and dried in vacuo,
40.0 mg, 1.67 mmol) in DMF (1.0 mL), Bn Br (300 lL,
2.52 mmol) was added at room temperature. After stir-
ring for 1 h, the mixture was poured into water and
extracted with EtOAc (·3). The extracts were combined,
washed with brine, dried over MgSO4, and concentrated
in vacuo. Purification of the residue by silica gel column
4.10. 2,3,4,6-Tetra-O-acetyl-a-D-5-deoxy-5-thiogluco-
pyranosyl trichloroacetimidate (11)
According to general procedure A, a solution of 4
(71.9 mg, 197 lmol) in CCl3CN (200 lL, 1.97 mmol)
was stirred with DBU (4.9 lL, 32.9 lmol) at 0 ꢁC for
15 min. The mixture was diluted with benzene and the
volatiles were removed in vacuo. Purification of the
residue by silica gel chromatography (EtOAc/hex-
ane = 25:75) gave 11 (77.2 mg, 152 lmol, 77%). 1H
NMR (CDCl3) d 2.00, 2.02, 2.06, 2.07 (each 3H, s,
CH3CO), 3.64 (1H, ddd, J = 3.4, 4.9, 11.2 Hz, C5H),
4.08 (1H, dd, J = 3.4, 12.2 Hz, C6HH), 4.39 (1H, dd,
J = 4.9, 12.2 Hz, C6HH), 5.31 (1H, dd, J = 2.9, 9.8 Hz,
C2H), 5.38 (1H, dd, J = 9.8, 11.2 Hz, C4H), 5.57 (1H,
t, J = 9.8, C3H), 6.36 (1H, d, J = 2.9 Hz, C1H), 8.78
chromatography (EtOAc/hexane 20:80) afforded
9
(124 mg, 1.47 mmol, 88%) as an amorphous solid. The
1H NMR spectrum indicated that this sample consists
of the two diastereomers due to the asymmetric center in
the THP group (50:50). IR (film) 2920, 2850, 1455, 1105,
1070, 970, 735, 700 cmÀ1. 1H NMR (CDCl3, Some signals
could not be assigned due to signals overlapping.) d 1.55–
1.95 (6H, C30H2, C40H2, C50H2), 3.22 (1H · 0.5, ddd,
J = 2.5, 3.9, 10.7 Hz, C5H), 3.57 (1H · 0.5, C60HH),
3.61 (1H · 0.5, C60HH), 3.85–4.15 (5H+1H · 0.5, C2H,
C3H, C4H, C6H2 (for both isomers), C5H (for one iso-
mer), 4.54–5.19 (8H, ArCH2O · 4), 7.15–7.40 (20H, aro-
matic protons). EI-MS (%, rel int) 539 (0.5, [MÀTHP]+),
538 (0.4, [MÀTHPOH]+), 91 (100, Bn+), 85 (59, THP+),
1
(1H, s, C( = NH)CCl3). The H NMR spectrum of this
sample had good accordance with that reported in the
literature.8
EI-HRMS
Found
m/z = 538.2184.
Calcd
for
4.11. 2,3,4,6-Tetra-O-benzoyl-5-deoxy-5-thio-a-D-gluco-
pyranosyl trichloroacetimidate (12)
C34H34O4S: [MÀTHPOH]+, 538.2178.
4.9. Tetrahydropyranyl 2,3,4,6-[tetrakis-O-(4-methoxy-
phenyl)methyl]-5-deoxy-5-thio-a-D-glucopyranoside (10)
According to general procedure A, a solution of 7
(596 mg, 854 lmol) in MeOH (10 mL) was stirred with
p-TsOH (3.0 mg, 15.8 lmol) at 45 ꢁC for 7 h. After neu-
tralization by the addition of Et3N (10 lL), the mixture
was concentrated in vacuo. Purification of the residue by
Tetraol 6a (261 mg, 932 lmol) was treated with MPMBr
(ca. 50% solution in toluene, 2.0 mL, ca. 5 mmol) in a

5124
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
silica gel column chromatography (EtOAc/benzene 4:96)
gave 2,3,4,6-tetra-O-benzoyl-5-deoxy-5-thio-a-D-gluco-
J = 10.7 Hz, ArCH2O), 4.87 (1H, d, J = 3.0 Hz, C1H),
7.15–7.40 (20H, aromatic protons). 13C NMR (CDCl3)
41.5, 68.0, 71.8, 73.2, 73.5, 75.8, 76.5, 82.2, 83.3, 84.7,
128.0, 128.1, 128.23, 128.27, 128.29, 128.39, 128.47,
128.52, 128.63, 128.66, 128.90, 128.96, 129.05, 129.08,
138.42, 138.47, 138.93, 139.44. FD-MS (%, rel int) m/z
557 (53, [M+H]+), 556 (100, M+), 539 (9.8, [MÀOH]+),
91 (32, Bn+). FD-HRMS Found m/z = 556.2285. Calcd
for C34H36O5S: M+, 556.2283. According to general pro-
cedure A, a solution of the alcohol (4.2 mg, 7.54 lmol) in
CCl3CN (500 lL, 4.95 mmol) with DBU (1.0 lL,
6.70 lmol) gave 14 (4.1 mg, 5.85 lmol, 78%) as a syrup.
1H NMR (CDCl3) d 3.39 (1H, ddd, J = 2.9, 3.9, 9.2 Hz,
C5H), 3.57 (1H, dd, J = 2.9, 10.3 Hz, C6HH), 3.88–4.00
(4H, C6HH, C4H, C2H, C3H), 4.49 (2H, s, ArCH2O),
4.57, 4.90 (each 1H, J = 10.2 Hz, ArCH2O), 4.65, 4.74
(each 1H, J = 11.7 Hz, ArCH2O), 4.80, 4.92 (each 1H,
J = 10.7 Hz, ArCH2O), 6.31 (1H, br, C1H), 7.15–7.30
(aromatic protons), 8.59 (1H, s, C(@NH)CCl3). This
sample was immediately used for the next glycosylation.
19
D
pyranose (443 mg, 728 lmol, 85%) as a syrup. ½aꢀ
+58.0ꢁ (c 0.36, CHCl3). IR (film) 3450, 1035, 2965,
1
1730, 1270, 1110, 1070, 705 cmÀ1. H NMR (CDCl3) d
2.62 (1H, br, OH), 4.15 (1H, dt, J = 4.9, 10.7 Hz,
C5H), 4.57, 4.65 (each 1H, dd, J = 4.9, 11.7 Hz,
C6H2), 5.49 (1H, br, C1H), 5.64 (1H, dd, J = 2.4,
9.8 Hz, C2H), 5.97 (1H, dd, J = 9.8, 10.7 Hz, C3H),
6.27 (1H, t, J = 10.7 Hz, C4H), 7.20-8.15 (20H, aromatic
protons). FD-MS (%, rel int) m/z 613 (26, [M+H]+), 612
(20, M+), 611 (39, [MÀH]+), 595 (29, [MÀOH]+), 491
(42, [MÀBzO]+), 105 (100, PhCO+). FD-HRMS Found
m/z = 612.1412. Calcd for C34H28O9S: M+, 612.1454.
According to general procedure A, a solution of the
product thus obtained (43.7 mg, 71.4 lmol) in CH2Cl2
(3.0 mL) was stirred with DBU (1.0 lL, 6.71 lmol)
and CCl3CN (100 lL, 990 lmol) at 0 ꢁC for 1 h. After
concentration in vacuo, purification of the residue by sil-
ica gel chromatography (EtOAc/hexane 5:95) gave 12
(36.0 mg, 47.8 lmol, 67%) as a syrup. 1H NMR (CDCl3)
d 4.07 (1H, ddd, J = 3.9, 4.9, 10.3 Hz, C5H), 4.55 (1H,
dd, J = 4.9, 12.2 Hz, C6HH), 4.63 (1H, dd, J = 3.9,
12.2 Hz, C6HH), 5.81 (1H, dd, J = 3.0, 10.8 Hz, C2H),
6.03 (1H, t, J = 10.8 Hz, C4H), 6.26 (1H, t,
J = 10.8 Hz, C3H), 6.64 (1H, d, J = 3.0 Hz, C1H),
4.14. 2,3,4,6-[Tetrakis-O-(4-methoxyphenyl)methyl]-5-
deoxy-5-thio-a-D-glucopyranosyl trichloroacetimidate
(15)
Treatment of 10 (600 mg, 789 lmol) in MeOH (50 mL)
with concentrated HCl (2.0 lL) gave the corresponding
alcohol (430 mg, 635 lmol, 81%) as a solid. Analytical
sample was obtained by recrystallization from EtOAc/
7.20–8.04
(aromatic
protons),
8.65
(1H,
s,
C(@NH)CCl3). This sample was immediately used for
the next glycosylation step.
hexane (40:60) to give colorless needles. mp 103–
26
D
2955, 2835, 1610, 1510, 1461, 1305, 1250, 1095, 1075,
4.12. 2,3,4,6-Tetra-O-pivaloyl-5-deoxy-5-thio-a-D-gluco-
pyranosyl trichloroacetimidate (13)
107 ꢁC. ½aꢀ +31ꢁ (c 0.94, CHCl3). IR (KBr) 3485,
1
1025 cmÀ1. H NMR (CDCl3) d 2.74 (1H, br, C1OH),
Treatment of 8 (32.6 mg, 53.7 lmol) with p-TsOH
(3.0 mg) in MeOH (1.0 mL), followed by reacting with
CCl3CN (16.3 lL, 113 lmol) according to general proce-
dure A, gave 13 (21.6 mg, 32.8 lmol, 61% in two steps)
3.38 (1H, br d, J = 9.8 Hz, C5H), 3.55 (1H, dd,
J = 2.9, 9.8 Hz, C6HH), 3.74, 3.77, 3.77, 3.78 (each
3H, s, CH3O), 3.74 (1H, dd, J = 2.9, 8.8 Hz, C2H),
3.75 (1H, t, J = 9.8 Hz, C4H), 3.80 (1H, dd, J = 8.8,
9.8 Hz, C3H), 3.87 (1H, dd, J = 4.4, 9.8 Hz, C6HH),
4.39, 4.46 (each 1H, d, J = 11.7 Hz, ArCH2O), 4.46,
4.75 (each 1H, d, J = 10.3 Hz, ArCH2O), 4.60, 4.66
(each 1H, d, J = 11.2 Hz, ArCH2O), 4.79, 4.83 (each
1H, d, J = 10.2 Hz, ArCH2O), 4.83 (1H, d, J = 2.9 Hz,
C1H), 6.80–7.26 (16H, aromatic protons). 13C NMR
(CDCl3) d 41.3, 55.09, 55.15, 67.3, 71.5, 72.5, 72.8,
75.0, 75.7, 81.5, 82.6, 84.0, 113.65, 113.67, 113.71,
113.8, 129.31, 129.34, 129.38, 129.6, 129.8, 130.0,
130.5, 131.1, 159.0, 159.1, 159.2, 159.3. FD-MS (%, rel
int) 676 (100, M+), 675 (49, [MÀH]+). FD-HRMS
Found m/z = 676.2688. Calcd for C38H44O9S: M+,
676.2706. According to general procedure A, treatment
of the alcohol (37.5 mg, 55.4 lmol) with DBU
(131 mmol/L solution in benzene, 21.4 lL, 0.1 equiv)
and CCl3CN (55.9 lL, 554 lmol) gave 15 (36.5 mg,
44.4 lmol, 80%) as a colorless syrup. IR (film) 3335,
2930, 2835, 1665, 1610, 1510, 1250, 1095, 1065, 1035,
820 cmÀ1. 1H NMR (C6D6) d 3.26, 3.28, 3.29, 3.30 (each
3H, s, CH3O), 3.54 (1H, dd, J = 2.9, 10.3 Hz, C6HH),
3.67 (1H, ddd, J = 2.9, 3.9, 10.2 Hz, C5H), 3.96 (1H,
dd, J = 3.9, 10.3 Hz, C6HH), 3.97 (1H, dd, J = 3.0,
9.3 Hz, C2H), 4.08 (1H, dd, J = 9.3, 10.2 Hz, C4H),
4.21 (1H, t, J = 9.3 Hz, C3H), 4.22, 4.29 (each 1H, d,
J = 11.8 Hz, ArCH2O), 4.42, 4.53 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.64, 5.03 (each 1H, d,
1
as a syrup. H NMR (CDCl3) d 1.10, 1.11, 1.17, 1.18
(each 9H, s, (CH3)3CCO), 3.64 (1H, ddd, J = 2.9, 5.4,
10.7 Hz, C5H), 4.11 (1H, dd, J = 5.4, 12.2 Hz, C6HH),
4.19 (1H, dd, J = 2.9, 12.2 Hz, C6HH), 5.32 (1H, dd,
J = 3.4, 9.8 Hz, C2H), 5.44 (1H, dd, J = 9.8, 10.7 Hz,
C4H), 5.61 (1H, t, J = 9.8 Hz, C3H), 6.30 (1H, d,
J = 3.4 Hz, C1H), 8.68 (1H, s, C(@NH)CCl3). This sam-
ple was immediately used for the next glycosylation step.
4.13. 2,3,4,6-Tetra-O-benzyl-5-deoxy-5-thio-a-D-gluco-
pyranosyl trichloroacetimidate (14)
Treatment of 9 (115 mg, 180 lmol) with HClO4 (10 mg,
100 lmol) in MeOH (1.0 mL) at room temperature for
3 h gave the corresponding alcohol (90.5 mg, 162 lmol,
27
D
3420, 3030, 2915, 2865, 1500, 1450, 1400, 1360, 1140,
90%) as a syrup. ½aꢀ +47ꢁ (c 0.76, CHCl3). IR (film)
1
1100, 1060, 1025, 735, 700 cmÀ1. H NMR (CDCl3) d
2.67 (1H, br, OH), 3.42 (1H, ddd, J = 3.0, 3.9, 9.7 Hz,
C5H), 3.59 (1H, dd, J = 3.0, 9.8 Hz, C6HH), 3.78 (1H,
dd, J = 3.0, 9.7 Hz, C2H), 3.81 (1H, t, J = 9.7 Hz,
C4H), 3.88 (1H, t, J = 9.7 Hz, C3H), 3.91 (1H, dd,
J = 3.9, 9.8 Hz, C6HH), 4.45, 4.48 (each 1H, d, J =
12.2 Hz, ArCH2O), 4.56, 4.90 (each 1H, d, J =
10.8 Hz, ArCH2O), 4.66, 4.71 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.81, 4.86 (each 1H, d,

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5125
J = 10.7 Hz, ArCH2O), 4.91, 5.06 (each 1H, d,
J = 10.8 Hz, ArCH2O), 6.56 (1H, d, J = 3.0, C1H),
6.73–7.33 (16H, aromatic protons), 8.55 (1H, s,
C(@NH)CCl3). This sample was gradually decomposed
in CDCl3, so that it was immediately used for the next
glycosylation.
for 23 h. The mixture was concentrated under reduced
pressure. Purification of the residue by silica gel column
chromatography (acetone/CH2Cl2 5:95) gave 5-deoxy-
5-thio-6-O-triphenylmethylglucopyranose
(156 mg,
356 lmol, 75%). 1H NMR (CDCl3) d 3.26–3.41 (3H,
C5H, C6H2), 3.61–3.72 (3H, C2H, C3H, C4H), 4.85
(1H, br, C1H) 7.15–7.40 (aromatic protons). This sam-
ple was used for the next step without purification. A
solution of 5-deoxy-5-thio-6-O-triphenylmethylgluco-
pyranose (52.0 mg, 119 lmol) in pyridine (1.0 mL) was
stirred with BzCl (90.0 lL, 714 lmol) at À15 ꢁC to
room temperature. After stirring for 4 h, MeOH was
added into the mixture. The resulting mixture was
poured into water and extracted with EtOAc (·3). Then
the combined organic layers were washed with brine,
dried over MgSO4, and concentrated in vacuo. Purifica-
tion of the residue by silica gel column chromatography
(EtOAc/hexane 10:90) afforded 1,2,3,4-tetra-O-benzoyl-
5-deoxy-5-thio-6-O-triphenylmethyl-D-glucopyranose
(79.0 mg, 92.8 lmol, 78%). The 1H NMR spectrum
indicated that the sample consists of a mixture of
anomers (a:b = 75:25). 1H NMR (CDCl3, a = 0.75,
b = 0.25) d 3.36 (1H · a, dd, J = 2.9, 9.8 Hz, C6H (a-
anomer)), 3.44 (1H · a, dd, J = 3.9, 9.8 Hz, C6H (a-an-
omer)), 3.40–3.52 (3H · b, C5H, C6H2(b-anomer)), 3.75
(1H, ddd, J = 2.9, 3.9, 10.3 Hz, C5H), 5.68 (1H · b, t,
J = 8.8 Hz, C2H (b-anomer)), 5.87 (1H · a, dd,
J = 2.9, 10.3 Hz, C2H (a-anomer)), 6.02–6.10 (2H · b,
C3H, C4H (b-anomer)), 6.11 (1H · a, t, J = 10.3 Hz,
C4H (a-anomer)), 6.14 (1H · a, t, J = 10.3 Hz, C3H
(a-anomer)), 6.41 (1H · b, d, J = 8.8 Hz, C1H (b-ano-
mer)), 6.63 (1H · a, d, J = 2.9 Hz, C1H (a-anomer)),
7.04–8.12 (aromatic protons). A solution of the product
thus obtained (38.0 mg, 44.5 lmol) in MeOH (2.0 mL)
was stirred with p-TsOH (2.0 mg) at room temperature.
After stirring for 3 h, the mixture was neutralized by the
addition of Et3N and concentrated in vacuo. Then, the
residue was diluted with EtOAc, poured into water, and
extracted with EtOAc (·3). The combined organic ex-
tracts were washed with brine, dried over MgSO4, and
concentrated in vacuo. Purification of the residue by sil-
ica gel column chromatography (EtOAc/hexane 20:80)
4.15. 1,2,3,6-Tetra-O-benzoyl-5-deoxy-5-thio-D-gluco-
pyranose (18)
A solution of 5-thioglucose (90.2 mg, 460 lmol) in pyr-
idine (500 lL) was stirred with BzCl (120 lL,
1.03 mmol) at room temperature. After stirring for 1 h,
additional BzCl (120 lL, 1.03 mmol) was added into
the mixture at the same temperature and the resulting
mixture was stirred for further additional 30 min.
MeOH was added into the mixture and the resulting
mixture was poured into water. The mixture was
extracted with EtOAc (·3). Then the combined organic
layers were washed with brine, dried over MgSO4, and
concentrated in vacuo. Purification of the residue by sil-
ica gel column chromatography (EtOAc/hexane 20:80)
gave an anomeric mixture of 18 (110 mg, 180 lmol,
40%) as a syrup. The anomeric mixture was subjected
to a medium pressure column chromatography to give
a-anomer (65.2 mg) and b-anomer (44.3 mg).
26
4.15.1. Physical data for a-anomer of 18. ½aꢀ +226ꢁ
D
(c 0.41, CHCl3), IR (film) 3470, 3065, 2960, 2920, 2855,
1725, 1600, 1450, 1265, 1105, 1025, 705 cmÀ1 1H
,
NMR (CDCl3) d 3.74 (1H, ddd, J = 2.9, 3.9, 10.3 Hz,
C5H), 4.18 (1H, t, J = 10.3 Hz C4H), 4.48 (1H, dd,
J = 2.9, 12.2 Hz, C6HH) 5.16 (1H, dd, J = 3.9, 12.2 Hz,
C6HH), 5.75 (1H, dd, J = 3.4, 10.3 Hz, C2H), 6.00
(1H, t, J = 10.3 Hz, C3H), 6.55 (1H, d, J = 3.4 Hz,
C1H), 7.21–8.11 (20H, aromatic protons), FD-MS (%,
rel int) 613 (58, [M+H]+), 612 (41, M+), 611 (48,
[MÀH]+), 507 (34, [MÀPhCO]+), 491 (58, [MÀBzO]+),
105 (100, PhCO+), FD-HRMS Found m/z = 613.1522,
Calcd for C34H29O9S: [M+H]+, 613.1532.
26
4.15.2. Physical data for b-anomer of 18. ½aꢀ +33ꢁ
D
(c 0.23, CHCl3), IR (film) 3065, 2960, 2920, 2855, 1725,
1
afforded 19 (22.0 mg, 36.0 lmol, 81%). The spectrum
1600, 1450, 1265, 1105, 1025, 705 cmÀ1
,
1H NMR
disclosed that this sample consists of a mixture of
anomers (a/b 83:17). 1H NMR (CDCl3, signals for
the major isomer and some signals for the minor iso-
mer are only described. a = 0.83, b = 0.17) d 3.02 (1H,
br, C6OH), 3.43 (1H · b, dt, J = 2.8, 10.7 Hz, C5H (b-
anomer)), 3.63 (1H · a, ddd, J = 2.5, 2.9, 10.7 Hz,
C5H (a-anomer)), 3.77 (1H · a, dd, J = 2.5, 13.2 Hz,
C6HH (a-anomer)), 3.92 (1H · a, dd, J = 2.9,
13.2 Hz, C6HH (a-anomer)), 5.74 (1H · b, t,
J = 9.3 Hz, C4H(b-anomer)), 5.77 (1H · a, dd,
J = 9.7, 10.7 Hz, C4H(a-anomer)), 5.84 (1H · a, dd,
J = 2.9, 10.3 Hz, C2H (a-anomer)), 5.91 (1H · b, t,
J = 9.3 Hz, C2H (b-anomer) or C3H(b-anomer)),
6.06 (1H · b, t, J = 9.3 Hz, C2H (b-anomer) or C3H
(b-anomer)), 6.34 (1H · a, dd, J = 9.7, 10.3 Hz, C3H
(a-anomer)), 6.44 (1H · b, d, J = 9.3 Hz, C1H (b-ano-
mer)), 6.63 (1H · a, d, J = 2.9 Hz, C1H (a-anomer)),
(CDCl3) d 3.48 (1H, dd, J = 3.4, 4.8, 8.8 Hz, C5H),
4.17 (1H, t, J = 8.8 Hz, C4H), 4.61 (1H, dd, J = 3.4,
11.7 Hz, C6HH), 5.04 (1H, dd, J = 4.8, 11.7 Hz,
C6HH), 5.49 (1H, t, J = 8.8 Hz, C2H), 5.94 (1H, t,
J = 8.8 Hz, C3H), 6.35 (1H, d, J = 8.8 Hz, C1H), 7.24–
7.56 (12H, aromatic protons), 7.83 (2H, d, J = 8.3 Hz,
aromatic protons), 7.93 (4H, d, J = 8.3 Hz, aromatic pro-
tons), 8.04 (2H, d, J = 8.3 Hz, aromatic protons), FD-MS
(%, rel int) 613 (20, [M+H]+), 612 (15, M+), 611 (15,
[MÀH]+), 507 (15, [MÀPhCO]+), 491 (21, [MÀBzO]+),
105 (100, PhCO+), FD-HRMS Found m/z = 613.1545,
Calcd for C34H29O9S: [M+H]+, 613.1532.
4.16. 1,2,3,4-Tetra-O-benzoyl-5-deoxy-5-thio-a-D-
glucopyranose (19)
1
4.16.1. Preparation from 5-thioglucose. A solution of
5-thioglucose (93.0 mg, 474 lmol) in pyridine (300 lL)
was stirred with TrCl (400 mg, 1.43 mmol) at 60 ꢁC
7.22–8.18 (20H, aromatic protons). The H NMR sig-
nals for the major isomer consisted of that prepared
as described below.

5126
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
4.16.2. Preparation from 6a. A mixture of 6a (41.0 mg,
146 lmol), TBDPSCl (114 lL, 439 lmol), and imidazole
(29.9 mg, 439 lmol) in DMF (0.5 mL) was stirred at
room temperature for 1 h. The mixture was poured into
water and extracted with Et2O. The combined extracts
were washed with brine, dried over MgSO4, and then
concentrated in vacuo. Purification of the residue by sil-
ica gel column chromatography (acetone/CH2Cl2 20:80)
gave tetrahydropyranyl 6-O-tert-butyldiphenylsilyl-5-
deoxy-5-thio-a-D-glucopyranoside (57.3 mg, 111 lmol,
76%) as a mixture of diastereomers due to the asymmet-
ric center in the THP moiety (50:50). 1H NMR (CDCl3)
d 1.05 (9H, s, (CH3)3Si), 1.50–1.82 (6H, C30H2, C40H2,
C50H2), 3.09 (1H · 0.5, dt, J = 4.9, 10.3 Hz, C5H),
3.31 (1H · 0.5, ddd, J = 4.4, 5.8, 9.8 Hz, C5H), 3.50–
3.56 (2H · 0.5, C06HH), 3.67, 3.71 (each 1H · 0.5, t,
J = 9.3 Hz, C3H), 3.78–3.91 (8H · 0.5, C2H, C4H,
C6HH, C60HH), 3.98, 4.01 (each 1H · 0.5, dd, J = 4.4,
10.3 Hz, C6HH), 4.83, 4.97 (each 1H · 0.5, d, both
J = 3.4 Hz, C1H), 4.92, 4.96 (each 1H · 0.5, br t,
J = 2.9 Hz, C20H), 7.36–7.43 (6H, aromatic protons),
7.66 (4H, aromatic protons). A solution of the silyl ether
thus obtained (12.9 mg, 26.5 lmol) in pyridine (0.5 mL)
was stirred with BzCl (15.4 lL, 133 lmol) at room tem-
perature for 2 h. The mixture was poured into water and
extracted with EtOAc. The combined extracts were
washed with brine, dried over MgSO4, and concentrated
in vacuo. Purification of the residue by silica gel column
chromatography (EtOAc/hexane 20:80) gave tetrahy-
dropyranyl 2,3,4-tri-O-benzoyl-6-O-tert-butyl-diphenyl-
7.16 (3H, aromatic protons), 7.26 (7H, aromatic protons),
7.40 (4H, aromatic protons), 7.58, 7.75, 7.78, 7.87 (each
2H, dd, J = 1.5, 8.3 Hz, aromatic protons). FD-MS (%,
rel int) 747 (5, [M+H]+), 729 (3, [MÀOH]+), 689 (100,
for C43H43O8SSi: [M+H]+, 747.2448. A solution of the
alcohol thus obtained (213 mg, 290 lmol) in a mixture
of pyridine (1.0 mL) and CH2Cl2 (2.0 mL) was stirred
with BzCl (50.0 mg, 356 lmol) at room temperature
for 12 h. The mixture was poured into saturated aque-
ous NaHCO3 solution and extracted with EtOAc. The
combined extracts were washed with brine, dried over
MgSO4, and concentrated in vacuo. Purification of the
residue by silica gel column chromatography (EtOAc/
hexane 18:82) gave 1,2,3,4-tetra-O-benzoyl-6-O-tert-
t
[MÀ Bu]+). FD-HRMS Found m/z = 747.2451. Calcd
butyldiphenylsilyl-5-deoxy-5-thio-a-D-glucopyranose
19
D
(240 mg, 281 lmol, 97%) as a syrup. ½aꢀ +202ꢁ (c 0.86,
CHCl3). IR (film) 3070, 2960, 2860, 1730, 1285, 1260,
1105, 1090, 1065, 705 cmÀ1. NMR (CDCl3) d 1.07
(9H, s, (CH3)3CSi), 3.72–3.76 (2H, C5H, C6HH), 4.01
(1H, dd, J = 3.9, 11.2 Hz, C6HH), 5.87 (1H, dd,
J = 2.9, 9.7 Hz, C2H), 6.15, 6.23 (each 1H, t,
J = 9.7 Hz, C3H, C4H), 6.65 (1H, d, J = 2.9 Hz, C1H),
7.07 (2H, t, J = 7.3 Hz, aromatic protons), 7.24 (3H, aro-
matic protons), 7.35 (11H, aromatic protons), 7.50 (4H,
aromatic protons), 7.62 (2H, aromatic protons), 7.83
(4H, br d, J = 7.5 Hz, aromatic protons), 7.89 (2H, dd,
J = 1.5, 7.5 Hz, aromatic protons), 8.13 (2H, dd,
J = 1.5, 7.5 Hz, aromatic protons). FD-MS (%, rel int)
t
851 (0.7, [M+H]+), 793 (100, [MÀ Bu]+), 729 (31,
silyl-5-deoxy-5-thio-a-D-glucopyranoside
(21.5 mg,
[MÀPhCOO]+). FD-HRMS Found m/z = 851.2693.
Calcd for C50H47O9SSi: [M+H]+, 851.2710. A mixture
of the tetrabenzoate thus obtained (210 mg, 247 lmol),
AcOH (50 mg, 833 lmol), and TBAF (1.0 M in THF,
0.4 mL) was stirred at room temperature for 12 h. The
mixture was poured into water and extracted with
EtOAc. The combined extracts were washed with brine,
dried over MgSO4, and then concentrated in vacuo.
Purification of the residue by silica gel column chro-
26.0 lmol, 98%) as a mixture of diastereomers due to
the asymmetric center in the THP moiety (50:50). H
1
NMR (CDCl3) d 1.03 (9H, s, (CH3)3Si), 1.49–1.82
(6H, C03H2, C04H2, C05H2), 3.24 (1H · 0.5, br d,
J = 11.7 Hz, C06HH), 3.48–3.58 (3H · 0.5, C5H,
C6HH, C60HH) 3.55, 4.04 (each 1H · 0.5, br t,
J = 9.8 Hz, C06HH), 3.72 (1H · 0.5, dd, J = 2.9,
11.2 Hz, C6HH), 3.78 (2H · 0.5, br d, J = 9.8 Hz,
C6HH), 3.94 (1H · 0.5, br d, J = 10.3 Hz C5H), 4.81,
5.20 (each 1H · 0.5, br t, J = 2.9 Hz, C02H), 5.28, 5.38
(each 1H · 0.5, t, both J = 2.9 Hz, C1H), 5.61, 5.71
(each 1H · 0.5, dd, both J = 2.9, 9.8 Hz, C2H), 5.96,
5.99 (each 1H · 0.5, t, both J = 9.8 Hz, C3H), 6.11,
6.14 (each 1H · 0.5, t, both J = 9.8 Hz, C4H), 7.08–
7.94 (25H, aromatic protons). A solution of the benzoyl
ester thus obtained (7.9 mg, 9.50 lmol) in MeOH
(1.0 mL) was stirred with HClO4 (1.0 lL) at room tem-
perature for 24 h. After neutralization by the addition of
Et3N (5 lL), the mixture was concentrated in vacuo.
Purification of the residue by silica gel column chromat-
ography (EtOAc/hexane 20:80) gave 2,3,4-tri-O-benzo-
matography (EtOAc/hexane 20:80) afforded 19
28
D
CHCl3). IR (film) 3451, 2960, 2855, 1730, 1280, 1260,
(140 mg, 227 lmol, 92%) as a syrup. ½aꢀ +121ꢁ (c 1.9,
1090, 710 cmÀ1 1H NMR (CDCl3) d 3.02 (1H, br,
.
C6OH), 3.66 (1H, ddd, J = 2.5, 2.9, 10.7 Hz, C5H),
3.81 (1H, dd, J = 2.5, 13.2 Hz, C6HH), 3.92 (1H, dd,
J = 2.9, 13.2 Hz, C6HH), 5.77 (1H, dd, J = 9.7,
10.7 Hz, C4H), 5.84 (1H, dd, J = 2.9, 10.3 Hz, C2H),
6.34 (1H, dd, J = 9.7, 10.3 Hz, C3H), 6.63 (1H, d,
J = 2.9 Hz, C1H), 7.20–8.14 (20H, aromatic protons).
FAB-MS (negative mode, %, rel int): 612 (3, MÀ), 611
(5, [MÀH]À), 368 (7, [MÀPhCOOH · 2]À), 121 (100,
PhCOOÀ);FAB-HRMS Found m/z = 611.1375. Calcd
for C34H27O9S: [MÀH]À, 611.1376.
yl-6-O-tert-butyldiphenylsilyl-5-deoxy-5-thio-a-D-gluco-
20
D
pyranose (5.8 mg, 7.70 lmol, 81%) as a syrup. ½aꢀ
+35.5ꢁ (c 0.39, CHCl3). IR (film) 3450, 3070, 2960,
2930, 2860, 1730, 1280, 1260, 1110, 1070, 1025, 730,
4.17.1,2,3,6-Tetra-O-acetyl-5-S-acetyl-glucofuranose(21)
705, 505 cmÀ1
.
1H NMR (CDCl3) d 0.98 (9H, s,
A solution of the diol 2020 (336 mg, 1.04 mmol) in a mix-
ture of Ac2O (5.0 mL) and pyridine (10 mL) was stirred at
room temperature for 1.5 h. The volatiles were azeotrop-
ically removed with toluene by rotary evaporator. Purifi-
cation of the residue by silica gel chromatography
(EtOAc/hexane 30:70) gave 21 (423 mg, 1.04 mmol,
100%). The 1H NMR spectra suggested that the product
(CH3)3CSi), 2.46 (1H, br, OH), 3.66 (1H, dd, J = 2.4,
10.7 Hz, C6HH), 3.71 (1H, ddd, J = 2.4, 3.9 Hz,
10.7 Hz, C5H), 3.90 (1H, dd, J = 3.9, 10.7 Hz, C6HH),
5.38 (1H, d, J = 2.8 Hz, C1H), 5.54 (1H, dd, J = 2.8,
10.2 Hz, C2H), 5.95, 6.10 (each 1H, t, J = 10.2 Hz,
C4H, C3H), 7.03 (2H, t, J = 7.3 Hz, aromatic protons),

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5127
20
is an anomeric mixture (75:25). IR (film) 1750, 1700, 1370,
1220, 1050, 1010, 940, 630 cmÀ1 1H NMR (CDCl3,
22 (28.2 mg, 77.2 lmol, 95%) and as a syrup. ½aꢀ
D
.
+174ꢁ (c 0.76, CHCl3). IR (film) 3480, 1750, 1370,
1
a = 0.75, b = 0.25) d 2.06, 2.07, 2.09, 2.11, 2.32 (each
3H · a, s, CH3CO (a-anomer)), 2.07, 2.08, 2.12, 2.125,
2.316 (each 3H · b, s, CH3CO (b-anomer)), 4.10
(1H · a, ddd, J = 4.4, 5.4, 9.3 Hz, C5H (a-anomer)),
4.18 (1H · b, ddd, J = 3.4, 4.4, 10.7 Hz, C5H
(b-anomer)), 4.27 (1H · a, dd, J = 5.3, 11.7 Hz, C6HH
(a-anomer)), 4.32 (1H · b, dd, J = 4.4, 11.7 Hz,
C6HH (b-anomer)), 4.42 (1H · a, dd, J = 4.4, 11.7 Hz,
C6HH (a-anomer)), 4.44 (1H · b, dd, J = 3.4, 11.7 Hz,
C6HH (b-anomer)), 4.51 (1H · b, dd, J = 4.4, 10.7 Hz,
C4H (b-anomer)), 4.52 (1H · a, dd, J = 4.4, 9.3 Hz,
C4H (a-anomer)), 5.08 (1H · b, s, C2H (b-anomer)),
5.20 (1H · a, dd, J = 2.4, 4.4 Hz, C2H (a-anomer)), 5.31
(1H · b, d, J = 4.4 Hz, C3H (b-anomer))5.47 (1H · a,
dd, J = 2.4, 4.4 Hz, C3H (a-anomer)), 6.09 (1H · b, s,
C1H (b-anomer)), 6.45 (1H · a, d, J = 4.4 Hz, C1H (a-
anomer)). EI-MS (%, rel int) 347 (10, [MÀAcO]+), 43
(100, CH3CO+). EI-HRMS Found m/z = 347.0772.
Calcd for C14H19O8S: [MÀAcO]+, 347.0801.
1220, 1025 cmÀ1. H NMR (CDCl3) d 2.00, 2.10, 2.12,
2.17 (each 3H, s, CH3CO), 3.24 (1H, d, J = 5.8 Hz,
C4OH), 3.40 (1H, ddd, J = 3.4, 4.4, 10.2 Hz, C5H),
3.76 (1H, dt, J = 5.8, 10.2 Hz, C4H), 4.22 (1H, dd,
J = 3.0, 12.2 Hz, C6HH), 4.74 (1H, dd, J = 4.4,
12.2 Hz, C6HH), 5.19 (1H, dd, J = 3.0, 10.2 Hz, C2H),
5.32 (1H, t, J = 10.2 Hz, C3H), 6.11 (1H, d,
J = 3.0 Hz, C1H). 13C NMR (CDCl3) d 20.5, 20.6,
20.7, 20.9, 42.5, 61.7, 70.9, 72.5, 72.6, 72.8, 169.1,
169.7, 170.9, 171.7. EI-MS (%, rel int) 304 (3,
[MÀAcOH]+), 245 (3, [MÀAcOHÀAcO]+), 244 (3,
[MÀAcOH · 2]+), 184 (30, [MÀAcOH · 3]+), 43 (100,
CH3CO+). EI-HRMS Found m/z = 304.0606. Calcd
for C12H16O7S: [MÀAcOH]+, 304.0617.
4.19. Glycosylation reaction of 5-thioglycosyl donors
carrying acyl protective group at C2-alcohols (Table 1)
4.19.1. Methyl 2,3,4-tri-O-benzoyl-6-O-[20,30,40,60-tetra-
O-acetyl-b-D-glucopyranosyl]-a-D-glucopyranoside (24)
(run 1). A mixture of 2331 (17.2 mg, 34.9 lmol), 16a
(15.3 mg, 30.2 lmol), and freshly activated powdered
MS4A (100 mg) in CH2Cl2 (1.0 mL) was stirred at room
temperature for 1 h. After the mixture was cooled to
À78 ꢁC, BF3OEt2 (2.1 lL, 17.5 lmol, 0.5 equiv) was
added to the suspension. After stirring for 2 h at
À78 ꢁC, the mixture was allowed to warm to room tem-
perature over an additional 1 h. Pyridine was added to
the mixture at À78 ꢁC and it was passed through silica
gel pad and then concentrated in vacuo. Purification
by silica gel column chromatography (EtOAc/hexane
25:75) gave 24 (22.2 mg, 26.5 lmol, 76%). The 1H
NMR spectrum indicated that this sample consists of
only b-isomer. 1H NMR (CDCl3) d 1.98, 1.99, 2.00,
2.07 (each 3H, s, CH3CO), 3.43 (3H, s, CH3O), 3.64–
3.70 (2H, C6HH, C50H), 4.03 (2H, C6HH, C60HH),
4.19–4.25 (2H, C5H, C60HH), 4.56 (1H, d, J = 8.3 Hz,
C10H), 5.02 (1H, t, J = 8.3 Hz, C20H), 5.04 (1H, t,
J = 9.8 Hz, C40H), 5.17–5.23 (3H, C1H, C2H, C30H),
5.39 (1H, t, J = 9.8 Hz, C4H), 6.11 (1H, t, J = 9.8 Hz,
C3H), 7.25–7.53 (9H, aromatic protons), 7.81–7.96
(6H, aromatic protons).
4.18. 1,2,3,6-Tetra-O-acetyl-5-deoxy-5-thio-D-glucopyra-
nose (22)
A solution of the pentaacetate 21 (199 mg, 491 lmol) in
DMF (3.0 mL) was stirred with hydrazine acetate
(136 mg, 1.47 mmol) at room temperature for 1 h. The
mixture was poured into water and extracted with
EtOAc (·3). The extracts were combined, washed with
brine, and dried over MgSO4. Purification of the residue
by silica gel chromatography (acetone/CH2Cl2 7:93)
gave 2,3,6-tri-O-acetyl-5-deoxy-5-thio-D-glucopyranose
(127 mg, 393 lmol, 80%). The 1H NMR spectra suggest-
ed that the product is an anomeric mixture (80:20). IR
(film) 3450, 2960, 1740, 1370, 1240, 1025 cmÀ1 1H
.
NMR (CDCl3, some signals for the minor b-isomer
could not be assigned. a = 0.8, b = 0.2) d 2.08, 2.09,
2.10 (each 3H · a, s, CH3CO (a-isomer)), 3.05 (1H · b,
ddd, J = 3.4, 4.9, 10.3 Hz, C5H (b-isomer)), 3.50
(1H · a, ddd, J = 2.9, 4.4, 10.8 Hz, C5H (a-isomer)),
3.74 (1H · a, t, J = 9.8 Hz, C4H (a-isomer)), 4.27
(1H · a, dd, J = 2.9, 11.7 Hz, C6HH (a-isomer)), 4.61
(1H · b, dd, J = 4.9, 11.7 Hz, C6HH (b-isomer)), 4.69
(1H · a, dd, J = 4.4, 11.7 Hz, C6HH (a-isomer)), 4.96
(1H · b, t, J = 9.8 Hz, C3H (b-isomer)) 5.11 (1H · a,
d, J = 3.0 Hz, C1H (a-isomer)), 5.13 (1H · a, dd,
J = 3.0, 9.8 Hz, C2H (a-isomer)), 5.40 (1H · a, t,
J = 9.8 Hz, C3H(a-isomer)). EI-MS (%, rel int) 323
(0.7, [M+H]+), 305 (2, [MÀOH]+), 262 (2,
[MÀAcOH]+), 244 (16, [MÀAcOHÀOH]+), 43 (100,
CH3CO+). EI-HRMS Found m/z = 323.0789. Calcd
for C12H19O8S: [M+H]+, 323.0801. A mixture of the diol
thus obtained (26.2 mg, 81.3 lmol), AcCl (8.6 lL,
122 lmol), pyridine (6.3 lL, 89.4 lmol), and DMAP
(1.0 mg, 8.1 lmol) was stirred in CH2Cl2 (1.0 mL) with
at 0 ꢁC for 6 h. Methanol (100 lL) was added into the
mixture. After further stirring at room temperature for
30 min, the mixture was poured into H2O and extracted
with EtOAc (·3). The combined organic extracts were
washed with brine, dried over MgSO4, and then concen-
trated in vacuo. Purification of the residue by silica gel
column chromatography (acetone/CH2Cl2 10:90) gave
4.19.2. Methyl 6-O-[20,30,40,60-tetra-O-acetyl-50-deoxy-
50-thio-D-glucopyranosyl]-2,3,4-tri-O-benzoyl-a-D-gluco-
pyranoside (25) (run 2). According to general procedure
B, treatment of 11 (16.5 mg, 32.4 lmol) with 16a
(16.4 mg, 32.4 lmol) and BF3OEt2 (1.0 lL) in CH2Cl2
(700 lL) afforded 25 (5.3 mg, 4.54 lmol, 19%) as a syr-
1
up. The H NMR spectrum indicated that this sample
consists
of
a
diastereomixture
of
anomers
(a:b = 30:70). Analytical samples were obtained by pre-
parative silica gel TLC (EtOAc/benzene/hexane
20:40:40).
22
D
4.19.2.1. Physical data for a-anomer of 25. ½aꢀ
+101ꢁ (c 0.15, CHCl3), Rf = 0.50 (above conditions),
IR (film) 2920, 2850, 1730, 1220, 1095, 1030,
710 cmÀ1 1H NMR (CDCl3) d 1.99, 2.01, 2.04, 2.06
,
(each 3H, s, CH3CO), 3.49 (3H, s, CH3O), 3.54 (1H,
dd, J = 1.7, 10.7 Hz, C6HH), 3.54 (1H, ddd, J = 2.9,

5128
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
4.9, 10.3 Hz, C05H), 3.97 (1H, dd, J = 2.9, 12.2 Hz,
C60HH), 4.04 (1H, dd, J = 6.4, 10.7 Hz, C6HH),
4.28 (1H, ddd, J = 1.7, 6.4, 9.8 Hz, C5H), 4.33 (1H,
dd, J = 4.9, 12.2 Hz, C60HH), 4.83 (1H, d,
J = 2.9 Hz, C10H), 5.16 (1H, dd, J = 2.9, 9.8 Hz,
C20H), 5.20–5.25 (2H, C1H, C2H), 5.28 (1H, dd,
J = 9.8, 10.3 Hz, C40H), 5.51 (1H, t, J = 9.8 Hz,
C4H), 5.53 (1H, t, J = 9.8 Hz, C30H), 6.13 (1H, t,
J = 9.8 Hz, C3H), 7.26–7.52 (9H, aromatic protons),
7.84–7.97 (6H, aromatic protons), FD-MS (%, rel int)
852 (18, M+), 105 (100, PhCO+).
15.9 lmol) with 16a (8.0 mg, 15.8 lmol) and BF3OEt2
(2.0 lL, 15.9 lmol) gave 27 (13.5 mg, 12.4 lmol, 77%)
as a syrup. The H NMR spectrum indicated that this
sample consists of a diastereomixture of anomers
(a:b = 17:83). Analytical samples were obtained by pre-
parative silica gel TLC (EtOAc/benzene 10:90).
1
4.19.4.2. Treatment with TESOTf (run 7). Accord-
ing to general procedure B, treatment of 12 (16.6 mg,
21.9 lmol) with 16a (13.9 mg, 27.0 lmol) and TESOTf
(110 lmol/mL solution in CH2Cl2, 10 lL, 0.05 equiv)
in CH2Cl2 (1.0 mL) gave 27 (9.2 mg, 7.99 lmol,
38%) as a syrup. The 1H NMR spectrum indicated
that this sample consists of a diastereomixture of
anomers (a:b = 84:16). Analytical samples were ob-
tained by preparative silica gel TLC (EtOAc/benzene
10:90).
26
D
4.19.2.2. Physical data for b-anomer of 25. ½aꢀ +23ꢁ
(c 0.16, CHCl3), Rf = 0.40 (above conditions), IR (film)
2920, 2850, 1730, 1220, 1095, 1030, 710 cmÀ1, 1H NMR
(CDCl3) d 2.00, 2.00, 2.02, 2.06 (each 3H, s, CH3CO),
3.12 (1H, ddd, J = 3.9, 5.4, 9.8 Hz, C05H), 3.44 (3H, s,
CH3O), 3.67 (1H, dd, J = 6.8, 10.7 Hz, C6HH), 3.94
(1H, dd, J = 1.9, 10.7 Hz, C6HH), 4.10 (1H, dd,
J = 3.9, 11.7 Hz, C60HH), 4.18 (1H, ddd, J = 1.9, 6.8,
9.8 Hz, C5H), 4.24 (1H, dd, J = 5.4, 11.7 Hz, C60HH),
4.68 (1H, d, J = 8.8 Hz, C10H), 5.06 (1H, dd, J = 8.8,
9.3 Hz, C30H), 5.17 (1H, d, J = 3.4 Hz, C1H), 5.20
(1H, dd, J = 3.4, 9.8 Hz, C2H), 5.27 (1H, dd, J = 9.3,
9.8 Hz, C40H), 5.32 (1H, t, J = 8.8 Hz, C20H), 5.40
(1H, t, J = 9.8 Hz, C4H), 6.10 (1H, t, J = 9.8 Hz,
C3H), 7.24–7.53 (9H, aromatic protons), 7.81–7.96
(6H, aromatic protons), FD-MS (%, rel int) 853 (59,
[M+H]+), 852 (36, M+), 794 (1.23, [M+HÀAcO]+), 793
(1.51, [MÀAcO]+), 732 (31, [M+HÀBzO]+), 105 (83,
PhCO+), FD-HRMS Found m/z = 852.2278. Calcd for
C42H44O17S: M+, 852.2299.
4.19.4.3. Activation with TMSOTf (run 8). According
to general procedure B, treatment of 12 (13.5 mg,
17.8 lmol) with 16a (9.0 mg, 17.8 lmol) and TMSOTf
(89.0 lmol/mL solution in CH2Cl2, 10 lL, 0.05 equiv)
1
gave 27 (2.2 mg, 1.96 lmol, 11%) as a syrup. The H
NMR spectrum indicated that this sample consists of
only a-isomer.
4.19.4.4. Activation with TfOH (run 9). According to
general procedure B, treatment of 12 (15.6 mg,
20.6 lmol) with 15 (10.4 mg, 20.6 lmol) and TfOH
(20.6 lmol/mL in CH2Cl2 solution, 1.0 lL, 0.01 equiv)
1
gave 27 (7.5 mg, 6.80 lmol, 33%) as a syrup. The H
NMR spectrum indicated that this sample consists of
a diastereomixture of anomers (a:b = 89:11). Analytical
samples were obtained by preparative silica gel TLC
(EtOAc/benzene 10:90).
4.19.3. 6-O-[20,30,40,60-Tetra-O-acetyl-50-deoxy-50-thio-
a-D-glucopyranosyl]-1,2,3,4-tetra-O-benzoyl-5-deoxy-5-
thio-a-D-glucopyranose (26) (run 3). According to general
procedure B, treatment of 11 (5.8 mg, 11.4 lmol) with 19
(7.0 mg, 11.4 lmol) and TESOTf (114 lmol/mL solution
18
4.19.4.5. Physical data for a-anomer of 27. ½aꢀ +136ꢁ
D
(CHCl3, c 0.75). Rf = 0.70 (above conditions). IR (film)
2960, 2930, 1730, 1450, 1270, 1105, 1070, 1025,
in CH2Cl2, 10 lL, 0.1 equiv) in CH2Cl2 (200 lL) affor-
26
D
(c 0.18, CHCl3). IR (film) 1735, 1250, 1225, 1090,
1
ded 26 (1.0 mg, 1.1 lmol, 10%) as a syrup. ½aꢀ +136
710 cmÀ1. H NMR (CDCl3) 3.51 (3H, s, CH3O), 3.64
(1H, dd, J = 1.5, 11.2 Hz, C6HH), 4.01 (1H, ddd,
J = 3.9, 4.9, 10.7 Hz, C05H), 4.30 (1H, ddd, J = 1.5,
6.1, 10.3 Hz, C6HH), 4.48 (1H, dd, J = 4.8, 12.2 Hz,
C06HH), 4.55 (1H, dd, J = 3.9, 12.2 Hz, C06HH), 5.07
(1H, dd, J = 3.9, 10.3 Hz, C2H), 5.15 (1H, d,
J = 2.9 Hz, C01H), 5.18 (1H, d, J = 3.9 Hz, C1H), 5.55
(1H, t, J = 9.8 Hz, C4H), 5.64 (1H, dd, J = 2.9,
10.3 Hz, C02H), 5.94 (1H, dd, J = 9.8, 10.7 Hz, C04H),
6.12 (1H, t, J = 9.8 Hz, C3H), 6.27 (1H, t, J = 9.8 Hz,
C03H), 7.20–8.06 (35H, aromatic protons). FD-MS (%,
rel int) 1101 (17, [M+H]+), 979 (27, [MÀBzO]+), 978
(17, [MÀBzOH]+), 105 (100, PhCO+). FD-HRMS
Found m/z = 1101.2983. Calcd for C62H53O17S:
[M+H]+, 1101.3004.
1
1025, 710 cmÀ1. H NMR (CDCl3) d 1.99, 2.03, 2.05,
2.08 (each 3H, s, CH3CO), 3.48 (1H, dd, J = 3.5,
10.7 Hz, C6HH), 3.56 (1H, dd, J = 3.0, 3.9, 10.8 Hz,
C05H), 3.82 (1H, dd, J = 3.0, 12.2 Hz, C06HH), 3.88
(1H, dt, J = 3.5, 10.3 Hz, C5H), 4.19 (1H, dd, J = 3.5,
10.7 Hz, C6HH), 4.44 (1H, dd, J = 3.9, 12.2 Hz,
C06HH), 4.73 (1H, J = 3.4 Hz, C01H), 5.07 (1H, dd,
J = 3.4, 9.8 Hz, C02H), 5.30 (1H, dd, J = 9.8, 10.8 Hz,
C04H), 5.54 (1H, t, J = 9.8 Hz, C03H), 5.86 (1H, dd,
J = 3.4, 10.3 Hz, C2H), 6.00 (1H, t, J = 10.3 Hz, C4H),
6.24 (1H, t, J = 10.3 Hz, C3H), 6.63 (1H, d,
J = 3.4 Hz, C1H), 7.23–8.17 (20H, aromatic protons).
FD-MS (%, rel int) 958 (17, M+), 899 ([MÀAcO]+),
853 (32, [MÀBz]+), 837 (28, [MÀPhCOO]+), 105 (100,
PhCO+);FD-HRMS Found = m/z 958.2147. Calcd for
C48H46O17S2: M+, 958.2176.
18
4.19.4.6. Physical data for b-anomer of 27. ½aꢀ +32ꢁ
D
(CHCl3, c 1.85). Rf = 0.65 (above conditions). IR (film)
1
2950, 1730, 1450, 1270, 1095, 1070, 1025, 710 cmÀ1. H
4.19.4. Methyl 6-O-[20,30,40,60-tetra-O-benzoyl-50-deoxy-
50-thio-D-glucopyranosyl]-2,3,4-tri-O-benzoyl-a-D-gluco-
pyranoside (27).
4.19.4.1. Activation with BF3OEt2 (run 4). According
to general procedure B, treatment of 12 (12.0 mg,
NMR (CDCl3) d 3.19 (3H, s, CH3O), 3.60 (1H, ddd,
J = 4.9, 5.4, 9.8 Hz, C05H), 3.75 (1H, dd, J = 6.8,
10.7 Hz, C6HH), 4.06 (1H, dd, J = 1.5, 10.7 Hz, C6HH),
4.18 (1H, ddd, J = 1.5, 6.8, 9.3 Hz, C5H), 4.53 (1H, dd,
J = 5.4, 11.7 Hz, C06HH), 4.64 (1H, dd, J = 4.9, 11.7 Hz,

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5129
C06HH), 4.93 (1H, d, J = 3.4 Hz, C1H), 5.05 (1H, d,
J = 7.8 Hz, C01H), 5.06 (1H, dd, J = 3.4, 10.3 Hz, C2H),
5.36 (1H, t, J = 9.3 Hz, C4H), 5.76 (1H, dd, J = 8.3,
8.8 Hz, C03H), 5.87 (1H, dd, J = 7.8, 8.3 Hz, C02H), 5.91
(1H, dd, J = 8.8, 9.8 Hz, C04H), 6.06 (1H, dd, J = 9.3,
10.3 Hz, C3H), 7.21–7.99 (35H, aromatic protons).
FD-MS (%, rel int) 1101 (26, [M+H]+), 1085 (26,
[MÀMe]+), 595 (15, 1-deoxy-thioglucose+), 105 (100,
PhCO+). FD-HRMS Found m/z = 1101.3022. Calcd for
C62H53O17S: [M+H]+, 1101.3004.
4.19.6.
1,2,3,4-Tetra-O-benzoyl-6-O-[20,30,40,60-tetra-
O-benzoyl-50-deoxy-50-thio-D-glucopyranosyl]-5-thio-a-D-
glucopyranose (29)
4.19.6.1. Activation with BF3OEt2 (run 6). According
to general procedure B, treatment of 12 (21.7 mg,
28.7 lmol) with 19 (16.0 mg, 26.1 lmol) BF3OEt2
(3.5 lL, 28.7 lmol) in CH2Cl2 (1.0 mL) gave 29
(19.5 mg, 16.2 lmol, 62%). The 1H NMR spectrum indi-
cated that this sample consists of only the b-anomer.
4.19.6.2. Activation with TESOTf (run 11). According
to general procedure B, treatment of 12 (33.1 mg,
43.7 lmol) with 19 (26.0 mg, 42.4 lmol) and TESOTf
(440 lmol/mL solution in CH2Cl2, 10 lL, 0.1 equiv) in
CH2Cl2 (1.0 mL) gave 29 (19.4 mg, 16.1 lmol, 38%).
4.19.5. 4-Nitrophenyl 2,3,4-tri-O-benzoyl-6-O-[20,30,40,60-
tetra-O-benzoyl-50-deoxy-50-thio-D-glucopyranosyl]-a-D-
glucopyranose (28) (run 5). According to general proce-
dure B, treatment of 12 (11.3 mg, 17.3 lmol) with 16b
(10.0 mg, 17.3 lmol) and BF3OEt2 (1.5 lL) in CH2Cl2
(700 lL) gave 28 (17.5 mg, 14.2 lmol, 82%). The 1H
NMR spectrum indicated that this sample consists of
a diastereomixture of anomers (a:b = 15:85). Analytical
samples were obtained by preparative silica gel TLC
(EtOAc/benzene 10:90).
1
The H NMR spectrum indicated that the sample con-
sists of a diastereomixture of anomers (a:b = 84:16).
Analytical samples were obtained by preparative silica
gel TLC (EtOAc/benzene 10:90).
20
4.19.6.3. Physical data for a-anomer of 29. ½aꢀ +210ꢁ
D
(c 0.65, CHCl3). Rf = 0.70 (above conditions). IR (film)
20
4.19.5.1. Physical data for a-anomer of 28. ½aꢀ +91ꢁ
1
3030, 2920, 1860, 1730, 1260, 1090, 1070, 705 cmÀ1. H
D
(c 2.2, CHCl3). Rf = 0.65 (above conditions). IR (film)
NMR (C6D6) d 3.53 (1H, dd, J = 2.9, 10.2 Hz, C6HH),
3.90 (1H, ddd, J = 2.9, 3.4, 10.7 Hz, C05H), 3.97 (1H,
ddd, J = 2.9, 3.9, 10.7 Hz, C5H), 4.35 (1H, dd, J = 3.9,
10.3 Hz, C6HH), 4.39 (1H, dd, J = 3.4, 12.2 Hz,
C06HH), 4.51 (1H, dd, J = 3.9, 12.2 Hz, C06HH), 4.97
(1H, d, J = 3.0 Hz, C01H), 5.58 (1H, dd, J = 3.0,
10.2 Hz, C02H), 5.89 (1H, dd, J = 3.4, 10.3 Hz, C2H),
5.98 (1H, dd, J = 9.7, 10.7 Hz, C04H), 6.17 (1H, t,
J = 9.8 Hz, C4H), 6.24 (1H, t, J = 9.8 Hz, C3H), 6.27
(1H, t, J = 9.8 Hz, C30H), 6.58 (1H, d, J = 3.4 Hz,
C1H), 7.20-8.20 (40H, aromatic protons). FD-MS (%,
rel int) 1207 (27, [M+H]+), 1101 (61, [MÀBz]+), 1085
(87, [MÀBzO]+), 105 (100, PhCO+). FD-HRMS Found
m/z = 1207.2858. Calcd for C68H55O17S2: [M+H]+,
1207.2881.
1725, 1595, 1520, 1450, 1270, 1105, 710 cmÀ1 1H
.
NMR (CDCl3) d 3.45 (1H, dd, J = 1.5, 11.7 Hz,
C6HH), 3.98 (1H, ddd, J = 3.9, 4.8, 10.3 Hz, C50H),
4.15 (1H, dd, J = 5.4, 10.7 Hz, C6HH), 4.34 (1H, ddd,
J = 1.5, 5.4, 10.3 Hz, C5H), 4.50 (1H, dd, J = 4.8,
11.7 Hz, C60HH), 4.58 (1H, dd, J = 3.9, 11.7 Hz,
C60HH), 5.13 (1H, d, J = 3.4 Hz, C10H), 5.28 (1H,
dd,J = 3.4, 10.3 Hz, C2H), 5.56 (1H, dd, J = 3.4,
10.3 Hz, C20H), 5.72 (1H, t, J = 10.3 Hz, C4H), 5.94
(1H, dd, J = 9.8, 10.3 Hz, C40H), 5.96 (1H, d,
J = 3.4 Hz, C1H), 6.21 (1H, t, J = 9.8 Hz, C30H), 6.31
(1H, t, J = 10.3 Hz, C3H), 7.16–7.56 (21H, aromatic pro-
tons), 7.78–8.26 (16H, aromatic protons). FD-MS (% rel
int) 1208 (3.4, [M+H]+), 1070 (100, [M+HÀPNPO]+),
1069 (24, [MÀPNPO]+), 138 (17, PNPO+), 105 (14,
PhCO+).
20
D
4.19.6.4. Physical data for b-anomer of 29. ½aꢀ
+115ꢁ (c 0.20, CHCl3). Rf = 0.65 (above conditions).
IR (film) 2920, 1730, 1450, 1260, 1090, 1070, 1025,
25
D
4.19.5.2. Physical data for b-anomer of 28. ½aꢀ +36ꢁ
1
(c 0.70, CHCl3). Rf = 0.60 (above conditions). IR (film)
1725, 1600, 1520, 1450, 1265, 1105, 710 cmÀ1. 1H NMR
(CDCl3) d 3.57 (1H, ddd, J = 1.9, 5.4, 8.8 Hz, C50H),
3.67 (1H, dd, J = 5.4, 10.7 Hz, C6HH), 4.06 (1H, dd,
J = 1.9, 10.7 Hz, C6HH), 4.24 (1H, ddd, J = 1.9, 5.4,
10.3 Hz, C5H), 4.52 (1H, dd, J = 5.9, 11.7 Hz,
C60HH), 4.66 (1H, dd, J = 5.4, 11.7 Hz, C60HH), 4.90
(1H, d, J = 6.8 Hz, C01H), 5.21 (1H, dd, J = 3.4,
10.3 Hz, C2H), 5.53 (1H, t, J = 10.3 Hz, C4H), 5.72
(1H, dd, J = 7.8, 8.8 Hz, C30H), 5.80 (1H, dd, J = 6.8,
7.3 Hz, C20H)), 5.87 (1H, t, J = 8.8 Hz, C40H), 5.92
(1H, d, J = 3.4 Hz, C1H), 6.25 (1H, t, J = 10.3 Hz,
C3H), 7.21 (2H, br d, J = 9.3 Hz, aromatic protons),
7.25–7.50 (15H, aromatic protons), 7.78–7.96 (20H, aro-
matic protons), 8.16 (2H, br d, J = 9.3 Hz, aromatic pro-
tons). FD-MS (%, rel int) 1207 (16, M+), 1086 (35,
[MÀBzO]+), 1070 (100, [M+HÀPNPO]+), 1069 (86,
[MÀPNPO]+), 138 (34, PNPO+), 105 (31, PhCO+),
FD-HRMS Found m/z = 1207.2955. Calcd for
C67H53O19NS: M+, 1207.2933.
705 cmÀ1. H NMR (CDCl3) d 3.55 (1H, dt, J = 5.4,
8.8 Hz, C05H), 3.72 (1H, dd, J = 5.9, 10.3 Hz,
C6HH), 3.86 (1H, ddd, J = 2.9, 5.9, 10.3 Hz, C5H),
4.14 (1H, dd, J = 2.9 Hz, 10.3 Hz, C6HH), 4.50, 4.59
(each 1H, dd, J = 5.4 Hz, 11.7 Hz, C06H2), 4.86 (1H,
d, J = 7.3 Hz, C01H), 5.49 (1H, dd, J = 3.4, 10.3 Hz,
C2H), 5.71 (2H, m, J = 7.3, 10.3 Hz, C4H, C03H),
5.80 (1H, t, J = 7.3 Hz, C02H), 5.87 (1H, t,
J = 9.8 Hz, C3H), 6.49 (1H, d, J = 3.4 Hz, C1H),
7.18–8.08 (40H, aromatic protons). FD-MS (%, rel
int) 1207 (5, [M+H]+), 1101 (20, [MÀBz]+), 1085 (36,
[MÀBzO]+), 595 (25, 1-deoxy-thioglucopyranose+),
105 (100, PhCO+). FD-HRMS Found m/z =
1207.2904. Calcd for C68H55O17S2: [M+H]+, 1207.2881.
4.19.7. Methyl 2,3,4-tri-O-benzoyl-6-O-[20,30,40,60-tetra-
O-pivaloyl-50-deoxy-50-thio-b-D-glucopyranosyl]-a-D-glu-
copyranose (30) (run 12). According to general procedure
B, treatment of 13 (13.9 mg, 20.5 lmol) with 16a
(10.0 mg, 20.5 lmol) and BF3OEt2 (3.0 lL) gave 30

5130
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
(14.4 mg, 14.1 lmol, 69%). The 1H NMR spectrum indi-
J = 3.9 Hz, C01H), 5.46 (1H, dd, J = 3.9, 9.8 Hz, C02H),
5.63 (1H, dd, J = 9.8, 10.3 Hz, C04H), 5.80 (1H, t,
J = 9.3 Hz, C3H), 5.87 (1H, t, J = 9.8 Hz, C03H), 6.25
(1H, d, J = 2.9 Hz, C1H), FD-MS (%, rel int) 711 (27,
[M+H]+), 710 (26, M+), 651 (100, [MÀAcO]+), 650 (86,
[MÀAcOH]+). FD-HRMS Found m/z = 710.1520. Calcd
for C28H38O17S2: M+, 710.1550.
cated that this sample consists of only the b-anomer.
26
½aꢀ +19ꢁ (c 1.5, CHCl3). IR (film) 2970, 1735, 1480,
D
1
1455, 1280, 1135, 710 cmÀ1. H NMR (CDCl3) d 1.09,
1,12, 1.12, 1.17 (each 9H, s, (CH3)3CCO), 3.08 (1H,
ddd, J = 2.9, 5.4, 10.3 Hz, C50H), 3.43 (3H, s, CH3O),
3.67 (1H, dd, J = 7.3, 10.3 Hz, C6HH), 3.87 (1H, dd,
J = 1.5, 10.3 Hz, C6HH), 4.07 (1H, dd, J = 5.4,
11.7 Hz, C60HH), 4.11 (1H, dd, J = 2.9, 11.7 Hz,
C60HH), 4.20 (1H, ddd, J = 1.5, 7.3, 10.3 Hz, C5H),
4.61 (1H, d, J = 8.8 Hz, C10H), 5.12 (1H, d,
J = 3.9 Hz, C1H), 5.13 (1H, t, J = 9.3 Hz, C30H), 5.19
(1H, dd, J = 3.9, 9.8 Hz, C2H), 5.29 (1H, t, J = 8.8 Hz,
C20H), 5.31 (1H, dd, J = 9.3, 10.3 Hz, C40H), 5.33
(1H, dd, J = 9.8, 10.3 Hz, C4H), 6.10 (1H, t,
J = 9.8 Hz, C3H), 7.23–7.52 (14H, aromatic protons),
7.80–7.96 (6H, aromatic protons). FD-MS (%, rel int)
1021 (36, [M+H]+), 1020 (11, M+), 919 (40, [MÀPivO]+),
105 (40, PhCO+), 85 (40, Piv+), 57 (100, (CH3)3C+), FD-
HRMS Found m/z = 1020.4170. Calcd for C54H68O17S:
M+, 1020.4177.
4.19.10. 4-O-[20,30,40,60-Tetra-O-acetyl-50-deoxy-50-thio-
a-D-glucopyranosyl]-1,2,3,6-tetra-O-benzoyl-5-deoxy-5-
thio-a-D-glucopyranose (33) (run 15). According to
general procedure B, treatment of 11 (10.4 mg,
16.2 lmol) with 18 (8.2 mg, 16.2 lmol) and TESOTf
(162 lmol/mL solution in CH2Cl2, 10 lL, 0.1 equiv) in
CH2Cl2 (400 lL) gave C2 deprotected a-glycoside 34
(0.1 mg) and acetate 35 (0.1 mg). Signals corresponding
to the desired disaccharide 33 were not detected in the
1H NMR spectrum.
4.19.10.1. Physical data of 4-O-[30,40,60-tri-O-acetyl-
50-deoxy-50-thio-a-D-glucopyranosyl]-1,2,3,6-tetra-O-benzo-
26
yl-a-D-glucopyranose (34). ½aꢀ +168ꢁ (c 0.14, CHCl3).
D
IR (film) 3455, 2920, 1725, 1265, 1105, 1070, 1025,
4.19.8. 4-Nitrophenyl 2,3,4-tri-O-benzoyl-6-O-[20,30,40,60-
tetra-O-pivaloyl-50-deoxy-50-thio-b-D-glucopyranosyl]-a-D-
glucopyranose (31) (run 13). According to general proce-
dure B, treatment of 13 (33.0 mg, 48.9 lmol) with 16b
1
710 cmÀ1. H NMR (CDCl3) d 1.94, 1.98, 2.01 (each
3H, s, CH3CO), 3.36 (1H, br, C50H), 3.62 (1H, br,
C20H), 3.80 (1H, dd, J = 2.9, 12.2 Hz, C60HH), 3.87
(1H, ddd, J = 3.4, 4.3, 10.3 Hz, C5H), 4.31 (1H, dd,
J = 4.3, 12.2 Hz, C60HH), 4.53 (1H, dd, J = 9.8,
10.3 Hz, C4H), 4.55 (1H, dd, J = 3.4, 11.7 Hz, C6HH),
4.77 (1H, dd, J = 4.3, 11.7 Hz, C6HH), 5.11 (1H, d,
J = 3.9 Hz, C10H), 5.13–5.16 (2H, C30H, C40H), 5.75
(1H, dd, J = 3.4, 10.3 Hz, C2H), 6.24 (1H, t,
J = 9.8 Hz, C3H), 6.56 (1H, d, J = 3.4 Hz, C1H), 7.16–
8.17 (15H, aromatic protons). FD-MS (%, rel int) 916
(18, M+), 857 (30, [MÀAcO]+), 811 (19, [MÀPhCO]+),
795 (18, [MÀBzO]+), 595 (35, [MÀthioglucose]+), 105
(100, PhCO+), FD-HRMS Found m/z = 916.2111.
Calcd for C46H44O16S2: M+, 916.2071.
(30.0 mg, 48.9 lmol) and BF3OEt2 (3.4 lL) gave 31
26
D
(47.7 mg, 42.1 lmol, 86%). ½aꢀ +48ꢁ (c 1.50, CHCl3).
IR (film) 2970, 1730, 1275, 1250, 1130, 1110, 1035,
710 cmÀ1. 1H NMR (CDCl3) d 1.09, 1.11, 1,12, 1.16 (each
9H, s, (CH3)3CCO), 3.08 (1H, ddd, J = 2.9, 5.4, 10.3 Hz,
C50H), 3.70 (1H, dd, J = 7.3, 10.7 Hz, C6HH), 3.88 (1H,
dd, J = 2.4, 10.7 Hz, C6HH), 4.05 (1H, dd, J = 5.4,
11.7 Hz, C60HH), 4.09 (1H, dd, J = 2.9, 11.7 Hz,
C60HH), 4.30 (1H, ddd, J = 2.4, 7.3, 9.8 Hz, C5H), 4.56
(1H, d, J = 8.3 Hz, C10H), 5.10 (1H, dd, J = 8.3, 9.3 Hz,
C30H), 5.25 (1H, t, J = 8.3 Hz, C20H), 5.29 (1H, dd,
J = 9.3, 10.3 Hz, C40H), 5.39 (1H, dd, J = 3.4, 10.3 Hz,
C2H), 5.50 (1H, t, J = 9.8 Hz, C4H), 5.92, (1H, d,
J = 3.4 Hz, C1H), 6.30 (1H, t, J = 10.3 Hz, C3H), 7.25–
7.53 (11H, aromatic protons), 7.84–7.85 (6H, aromatic
protons), 8.27 (2H, d, J = 9.3 Hz, aromatic protons).
FD-MS (%, rel int) 1128 (10, [M+H]+), 1127 (8.9, M+),
991 (100, [M+2HÀPNPO]+), 990 (53, [M+HÀPNPO]+),
989 (67, [MÀPNPO]+), 85 (40, Piv+), FD-HRMS Found
m/z = 1127.4178. Calcd for C59H69O19NS: M+, 1127.4185.
4.19.10.2. Physical data of 1,2,3,6-tetra-O-benzoyl-4-
O-acetyl-5-deoxy-5-thio-a-D-glucopyranose (35). ½aꢀ
22
D
+222ꢁ (c 0.33, CHCl3). IR (film) 2960, 2920, 1730,
1
1265, 1090, 1070, 1020, 710 cmÀ1. H NMR (CDCl3) d
1.90 (3H, s, CH3CO), 3.91 (1H, ddd, J = 3.4, 4.9,
10.3 Hz, C5H), 4.50 (1H, dd, J = 3.4, 12.2 Hz, C6HH),
4.58 (1H, dd, J = 4.9, 12.2 Hz, C6HH), 5.76 (1H, dd,
J = 3.4, 10.3 Hz, C2H), 5.78 (1H, t, J = 10.3 Hz, C4H),
6.11 (1H, t, J = 10.3 Hz, C3H), 6.58 (1H, d,
J = 3.4 Hz, C1H), 7.22–7.53 (12H, aromatic protons),
7.79, 7.90, 8.07, 8.11 (each 2H, d, J = 7.3 Hz, aromatic
protons), FD-MS (%, rel int) 654 (4.0, M+), 595 (19,
[MÀAcO]+), 549 (20, [MÀPhCO]+), 533 (77,
[MÀBzO]+), 105 (100, PhCO+).
4.19.9. 4-O-[20,30,40,60-Tetra-O-acetyl-50-deoxy-50-thio-a-
D -glucopyranosyl]-1,2,3,6-tetra-O-acetyl-5-deoxy-5-thio-
a-D-glucopyranose (32) (run 14). According to general
procedure B, treatment of 11 (20.8 mg, 40.9 lmol) with
22 (14.9 mg, 40.9 lmol) and TESOTf (402 lmol/mL solu-
tion in CH2Cl2, 10.2 lL, 0.1 equiv) in CH2Cl2 (400 lL)
26
D
(c 0.18, CHCl3). IR (film) 2960, 1750, 1375, 1045,
gave 32 (1.4 mg, 2.05 lmol, 5.0%) as a syrup. ½aꢀ +300ꢁ
4.19.11. 2,3,4,6-Tetra-O-pivaloyl-5-deoxy-5-thio-D-glucal
(36) (run 17). According to general procedure B, treat-
ment of 13 (31.8 mg, 47.0 lmol) with 17 (35.2 mg,
69.6 lmol) and BF3OEt2 (2.5 lL) in CH2Cl2 (1.0 mL)
gave 36 (2.5 mg, 4.7 lmol, 10%) as a syrup. Signals cor-
responding to the desired disaccharide were not detected
1
1020 cmÀ1. H NMR (C6D6) d 1.52, 1.61, 1.63, 1.66,
1.69, 1.71, 1.76, 1.92 (each 3H, s, CH3CO), 3.29 (1H,
ddd, J = 3.4, 5.4, 10.2 Hz, C5H), 3.63 (1H, ddd, J = 2.9,
3.9, 10.3 Hz, C05H), 4.08 (1H, dd, J = 3.4, 12.2 Hz,
C6HH), 4.15 (1H, dd, J = 9.3, 10.2 Hz, C4H), 4.21 (1H,
dd, J = 2.9, 12.2 Hz, C06HH), 4.26 (1H, dd, J = 5.4,
12.2 Hz, C6HH), 4.61 (1H, dd, J = 3.9, 12.2 Hz, C06HH),
5.22 (1H, dd, J = 2.9, 9.3 Hz, C2H), 5.36 (1H, d,
1
in the H NMR spectrum, and alchol 17 (29.4 mg) was
22
D
recovered. ½aꢀ +28ꢁ (c 0.11, CHCl3), IR (film) 2970,
1740, 1480, 1275, 1130 cmÀ1
,
1H NMR (CDCl3) d

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5131
1.18, 1.18, 1.20, 1.20 (each 9H, s, (CH3)3CCO), 3.54
(1H, dd, J = 5.9, 7.3, Hz, C5H), 4.23, (1H, dd, J = 5.9,
11.7 Hz, C6HH), 4.41 (1H, dd, J = 7.3, 11.7 Hz,
C6HH), 5.33 (1H, dd, J = 3.9, 5.9 Hz, C4H), 5.52 (1H,
d, J = 3.9 Hz, C3H), 6.02 (1H, s, C1H), FD-MS (%,
rel int) 515 (38, [M+H]+), 514 (100, M+), 430 (21,
[M+HÀPiv]+), 429 (67, [MÀPiv]+), 85 (75, Piv+), 57
(13, (CH3)3C+), FD-HRMS Found m/z = 514.2576.
Calcd for C26H42O8S: M+, 514.2600.
(each 1H, d, J = 10.8 Hz, ArCH2O), 4.69, 4.73 (each
1H, d, J = 11.7 Hz, ArCH2O), 4.78, 4.84 (each 1H, d,
J = 10.2 Hz, ArCH2O), 5.03 (1H, d, J = 1.9 Hz, C01H),
5.21 (1H, dd, J = 3.4, 10.3 Hz, C2H), 5.26 (1H, dd,
J = 9.2, 10.3 Hz, C3H), 6.07 (1H, d, J = 3.4 Hz, C1H),
7.12–7.35 (20H, aromatic protons). FD-MS (%, rel int)
903 (67, [M+H]+), 902 (87, M+), 901 (100, [MÀH]+),
843 (39, [MÀAcO]+), 795 (49, [MÀBnO]+). FD-HRMS
Found m/z = 902.3013. Calcd for C48H54O13S2: M+,
902.3006.
4.20. Glycosylation reaction of 5-thioglycosyl donor
bearing ethereal protective group at C2-alcohols (Table 3)
4.20.3. 1,2,3,4-Tetra-O-benzoyl-6-O-[20,30,40,60-[tetrakis-
O-(4-methoxyphenyl)methyl]-50-deoxy-50-thio-a-D-gluco-
pyranosyl]-5-deoxy-5-thio-a-D-glucopyranose (40) (run
3). According to general procedure B, treatment of 15
(3.4 mg, 4.1 lmol) with 19 (5.3 mg, 8.7 lmol,
a:b = 83:17) and TESOTf (20.5lmol/mL in CH2Cl2
solution, 10 lL, 0.05 equiv) gave 40 (4.9 mg, 3.9 lmol,
4.20.1.
1,2,3,4-Tetra-O-benzoyl-6-O-[20,30,40,60-tetra-
O-benzyl-50-deoxy-50-thio-a-D-glucopyranosyl]-5-deoxy-5-
thio-a-D-glucopyranose (38) (run 1). According to general
procedure B, a mixture of 14 (7.5 mg, 10.7 lmol) with 19
(9.5 mg, 15.5 lmol) and freshly activated powdered
MS4A (100 mg) in CH2Cl2 (0.5 mL) was stirred at room
temperature for 1 h. After the mixture was cooled to
À78 ꢁC, TESOTf (42.8 lmol/mL solution in CH2Cl2,
10 lL, 0.04 equiv) was added to the suspension. After
stirring for 2 h at À78 ꢁC, the mixture was allowed to
warm to room temperature over additional 1 h. Pyridine
was added to the mixture at À78 ꢁC and it was passed
through silica gel pad and then concentrated in vacuo.
Purification by silica gel column chromatography
1
94%) as a syrup. The H NMR spectrum disclosed that
this sample consists of an anomeric mixture at the C1
position (a:b = 83:17) however, b-isomer, due to the glu-
26
D
cosyl linkage newly formed, was not observed. ½aꢀ
+136ꢁ (c 0.28, CHCl3). IR (film) 2923, 1730, 1610,
1510, 1250, 1090, 710 cmÀ1. H NMR (CDCl3, signals
1
for the main isomer and some for the minor isomer
are described. Only for the signal of the minor isomer,
ꢂminor isomerꢁ is mentioned. a = 0.83, b = 0.17) d 3.13
(1H · a, dd, J = 2.9, 3.9, 10.7 Hz, C05H), 3.28 (1H · a,
dd, J = 2.9, 10.2 Hz, C06HH), 3.52 (1H · a, dd,
J = 2.9, 9.7 Hz, C6HH), 3.66 (1H · a, dd, J = 2.9,
9.8 Hz, C02H), 3.66–3.82 (2H · a, C03H, C04H), 3.73,
3.75, 3.78, 3.78 (each 3H · a, s, CH3O), 3.83 (1H · a,
dd, J = 3.9, 10.7 Hz, C06HH), 3.95–4.05 (2H · a, C5H,
C6HH), 4.21 (1H · a, d, J = 2.9 Hz, C01H),
4.25(1H · b, d, J = 2.9 Hz, C01H (minor isomer)), 4.32,
4.37 (each 1H · a, d, J = 11.8 Hz, ArCH2O), 4.42, 4.75
(each 1H · a, d, J = 10.3 Hz, ArCH2O), 4.47, 4.59 (each
1H · a, d, J = 11.7 Hz, ArCH2O), 4.66, 4.74 (each
1H · a, d, J = 10.2 Hz, ArCH2O), 5.78 (1H · a, dd,
J = 3.4, 10.3 Hz, C2H), 5.86 (1H · b, dd, J = 8.3,
9.8 Hz, C2H (minor isomer)), 5.87 (1H · a, t,
J = 10.3 Hz, C4H), 5.99 (1H · b, t, J = 8.8 Hz, C03H
or C40H (minor isomer)), 6.20 (1H · a, t, J = 10.3 Hz,
C3H), 6.39 (1H · b, d, J = 8.3 Hz, C1H (minor isomer)),
6.62 (1H · a, d, J = 3.4 Hz, C1H), 7.05–8.14 (36H, aro-
matic protons). 13C NMR (CDCl3) d 41.44, 41.47,
55.21, 55.26, 71.28, 71.92, 72.68, 72.76, 72.80, 74.14,
75.06, 75.71, 81.00, 81.52, 82.73, 83.89, 113.67, 113.71,
113.77, 113.81, 128.21, 128.28, 128.35, 128.72, 128.76,
129.23, 129.35, 129.48, 129.57, 129.72, 129.84, 129.97,
130.02, 130.46, 130.89, 131.43, 133.08, 133.24, 133.66,
133.84, 158.98, 159.10, 159.19, 159.26, 164.69, 165.20,
165.21, 165.85. FD-MS (%, rel int) 1271 (9.0,
[M+H]+), 1270 (13, M+), 1149 (100, [MÀPhCOO]+).
FD-HRMS Found m/z = 1270.4017. Calcd for
C72H70O17S2: M+, 1270.4054.
(EtOAc/hexane 25:75) gave 38 (10.0 mg, 8.67 lmol,
25
D
81%) as amorphous powder. ½aꢀ +109ꢁ (c 0.68, CHCl3).
IR (film) 2920, 2860, 1730, 1260, 1090, 1070, 705 cmÀ1
.
1H NMR (CDCl3) d 3.16 (1H, ddd, J = 2.4, 2.9, 10.3,
C05H), 3.32 (1H, dd, J = 2.4, 10.3 Hz, C06H), 3.52
(1H, dd, J = 2.9, 9.8 Hz, C6HH), 3.74 (1H, dd,
J = 2.9, 10.3 Hz, C02H), 3.78 (1H, t, J = 10.3 Hz,
C04H), 3.90 (1H, t, J = 10.3 Hz, C30H), 3.90 (1H, dd,
J = 2.9, 10.3 Hz, C06HH), 4.00 (1H, ddd, J = 2.9, 6.5,
10.3, C5H), 4.08 (1H, dd, J = 6.5, 9.8 Hz, C6HH), 4.32
(1H, d, J = 2.9 Hz, C01H), 4.40 (2H, s, ArCH2O), 4.55,
4.87 (each 1H, d, J = 10.7 Hz, ArCH2O), 4.57, 4.69
(each 1H, d, J = 12.2 Hz, ArCH2O), 4.77, 4.87 (each
1H, d, J = 10.7 Hz, ArCH2O), 5.82 (1H, dd, J = 2.9,
10.3 Hz, C2H), 5.94 (1H, t, J = 10.3 Hz, C4H), 6.24
(1H, t, J = 10.3 Hz, C3H), 6.64 (1H, d, J = 2.9 Hz,
C1H), 7.00–8.20 (40H, aromatic protons). FD-MS (%,
rel int) 1151 (65, [MH]+), 1150 (100, M+), 1043 (86,
[MÀBnO]+). FD-HRMS Found m/z = 1150.3633. Calcd
for C68H62O13S2: M+, 1150.3632.
4.20.2. 1,2,3,6-Tetra-O-acetyl-4-O-[20,30,40,60-tetra-O-
benzyl-50-deoxy-50-thio-a-D-glucopyranosyl]-5-deoxy-5-
thio-a-D-glucopyranose (39) (run 2). According to general
procedure B, treatment of 14 (9.0 mg, 11.9 lmol) with 22
(5.1 mg, 14.0 lmol) and TESOTf (59.5 lmol/mL in
CH2Cl2 solution, 10 lL, 0.05 equiv) gave 39 (10.1 mg,
25
D
11.2 lmol, 94%) as a syrup. ½aꢀ +119ꢁ (c 0.74, CHCl3).
IR (film) 3030, 2920, 2860, 1751, 1455, 1365, 1215, 1065,
740, 701 cmÀ1. 1H NMR (CDCl3) d 1.89, 1.97, 1.98, 2.16
(each 3H, s, CH3CO), 3.14 (1H, br, C05H), 3.50 (1H, dd,
J = 1.9, 9.7 Hz, C06HH), 3.60 (1H, ddd, J = 3.9, 4.4,
10.2 Hz, C5H), 3.79–3.84 (3H, C02H, C03H, C04H),
3.89 (1H, dd, J = 3.9, 9.7 Hz, C06HH), 4.34 (1H, dd,
J = 9.2, 10.2 Hz, C4H), 4.40–4.50 (2H, C6H2), 4.42,
4.45 (each 1H, d, J = 12.2 Hz, ArCH2O), 4.55, 4.88
4.20.4. Methyl 2,3,4-tri-O-benzoyl-6-O-[20,30,40,60-[tetra-
kis-O-(4-methoxyphenyl)methyl]-50-deoxy-50-thio-a-D-
glucopyranosyl]-a-D-glucopyranoside (41) (run 4).
According to general procedure B, treatment of 15
(9.9 mg, 12.1 lmol) with 16a (12.2 mg, 24.1 lmol)
and TESOTf (60.5 lmol/mL solution in CH2Cl2,

5132
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
10 lL, 0.05 equiv) gave 41 (11.5 mg, 9.90 lmol, 82%,
a:b = 88:12) as a syrup. Analytical sample was prepared
by preparative silica gel TLC (EtOAc/benzene 7:93).
4.20.5. 1,2,3,6-Tetra-O-acetyl-4-O-[20,30,40,60-[tetrakis-
O-(4-methoxyphenyl)methyl]-50-deoxy-50-thio-a-D-gluco-
pyranosyl]-5-deoxy-5-thio-a-D-glucopyranose (42), (run
5). According to general procedure B, treatment of 15
(7.6 mg, 9.3 lmol) with 22 (6.0 mg, 16.5 lmol) and TE-
26
4.20.4.1. Physical data for a-isomer of 41. ½aꢀ +74ꢁ
D
(c 0.55, CHCl3). Rf = 0.65 (above conditions). IR (film)
SOTf (46.5 lmol/mL, 10 lL, 0.05 equiv) gave 42
26
D
CHCl3). IR (film) 2915, 2850, 1750, 1610, 1510, 1245,
1
2930, 1730, 1510, 1250, 1095, 1065, 1030, 710 cmÀ1. H
(5.7 mg, 5.6 lmol, 60%) as a syrup. ½aꢀ +83ꢁ (c 0.40,
NMR (C6D6) d 3.12 (3H, s, C1OCH3), 3.28, 3.30, 3.310,
3.311 (each 3H, s, CH3O), 3.49 (2H, br d, J = 8.8 Hz,
C05H, C60HH), 3.57 (1H, dd, J = 2.0, 11.2 Hz,
C6HH), 3.96 (2H, br dd, J = 3.4, 9.8 Hz, C02H,
C06HH), 4.08 (1H, dd, J = 9.3, 9.8 Hz, C04H), 4.15
(1H, dd, J = 4.9, 11.2 Hz, C6HH), 4.23, 4.295 (each
1H, d, J = 11.7 Hz, ArCH2O), 4.298 (1H, t, J = 9.3 Hz,
C03H), 4.35 (1H, ddd, J = 1.9, 4.9, 10.3 Hz, C5H),
4.53, 4.59 (each 1H, d, J = 11.3 Hz, ArCH2O), 4.54
(1H, d, J = 3.4 Hz, C01H), 4.67, 5.070 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.95, 5.074 (each 1H, d,
J = 10.2 Hz, ArCH2O), 5.31 (1H, d, J = 3.4 Hz, C1H),
5.45 (1H, dd, J = 3.4, 10.3 Hz, C2H), 6.07 (1H, t,
J = 10.3 Hz, C4H), 6.64 (1H, t, J = 10.3 Hz, C3H),
6.73–8.15 (31H, aromatic protons). 13C NMR (C6D6) d
41.9, 54.70, 54.70, 54.73, 54.73, 55.2, 67.7, 68.1, 69.3,
70.0, 71.4, 72.4, 72.9, 75.3, 75.9, 72.8, 81.3, 82.5, 83.6,
85.2, 97.5, 113.89, 113.93, 114.07, 114.18, 128.41,
128.47, 128.53, 129.51, 129.56, 129.63, 129.68, 129.79,
129.81, 129.96, 130.16, 130.19, 130.7, 131.4, 131.9,
132.4, 132.9, 133.11, 133.14, 159.5, 159.6, 159.7, 159.8,
165.4, 165.8, 166.3. FD-MS (%, rel int) 1165 (15,
[M++H]+), 1164 (31, 1044 (28, [M+HÀMPM]+), 1043
1
1220, 1095, 1030, 821 cmÀ1. H NMR (C6D6) d 1.49,
1.61, 1.63, 1.64 (each 3H, s, CH3CO), 3.25, 3.256,
3.262, 3.27 (each 3H, s, CH3O), 3.54 (1H, ddd, J = 2.4,
4.4, 10.3 Hz, C05H), 3.60 (1H, ddd, J = 3.4, 5.4,
10.3 Hz, C5H), 3.67 (1H, dd, J = 2.4, 9.8 Hz, C06HH),
3.95 (1H, dd, J = 2.9, 9.3 Hz, C02H), 4.01 (1H, dd,
J = 4.4, 9.8 Hz, C06HH), 4.07 (1H, dd, J = 9.3,
10.3 Hz, C40H), 4.18 (1H, t, J = 9.3, C03H), 4.28, 4.31
(each 1H, d, J = 11.7 Hz, ArCH2O), 4.32 (1H, dd,
J = 8.8, 10.3 Hz, C4H), 4.54 (1H, dd, J = 5.4, 12.2 Hz,
C6HH), 4.60, 4.75 (each 1H, d, J = 11.7 Hz, ArCH2O),
4.65 (1H, dd, J = 3.4, 12.2 Hz, C6HH), 4.66, 5.01 (each
1H, d, J = 10.7 Hz, ArCH2O), 4.94, 4.98 (each 1H, d,
J = 10.7 Hz, ArCH2O), 5.14 (1H, d, J = 3.0 Hz, C01H),
5.40 (1H, dd, J = 2.9, 9.8 Hz, C2H), 5.88 (1H, dd,
J = 8.8, 9.8 Hz, C3H), 6.28 (1H, d, J = 2.9 Hz, C1H),
6.73-7.33 (16H, aromatic protons). FD-MS (%, rel int)
1023 (27, [MH]+), 1022 (19, M+), 1021 (22, [MÀH]+),
901 (100, [MÀMPM]+). FD-HRMS Found m/z =
1022.3392. Calcd for C52H62O17S2: M+, 1022.3428.
4.20.6. Methyl 2,3-di-O-benzoyl-6-O-(4-methoxy-phen-
yl)methyl-4-O-[20,30,40,60-tetrakis-O-(4-methoxy-phenyl)-
methyl-50-deoxy-50-thio-a-D-glucopyranosyl]-a-D-glucopy-
ranoside (43) (run 6). According to general procedure B,
treatment of 15 (46.7 mg, 56.9 lmol) with 17 (52.4 mg,
100 lmol) and TESOTf (210 lmol/mL solution in
(100,
[MÀMPM]+).
FD-HRMS
Found
m/z = 1164.4172. Calcd for C66H68O17S: M+, 1164.4177.
26
4.20.4.2. Physical data for b-isomer of 41. ½aꢀ +34ꢁ
D
(c 0.25, CHCl3). Rf = 0.60 (above conditions). IR (film)
2915, 1730, 1515, 1280, 1245, 1095, 1070, 1035,
CH2Cl2, 13.5 lL, 0.05 equiv) gave 43 (58.6 mg,
26
D
IR (film) 2950, 1725, 1610, 1515, 1275, 1250, 1100,
1
710 cmÀ1. H NMR (C6D6) d 2.88 (1H, ddd, J = 3.4,
49.6 lmol, 87%) as a syrup. ½aꢀ +78ꢁ (c 0.74, CHCl3).
4.9, 9.3 Hz, C05H), 3.10 (3H, s, C1OCH3), 3.297,
3.299, 3.299, 3.31 (each 3H, s, CH3O), 3.58 (1H, dd,
J = 7.8, 9.3 Hz, C03H), 3.62 (1H, dd, J = 3.4, 9.8 Hz,
C06HH), 3.82 (1H, dd, J = 4.9, 9.8 Hz, C06HH), 3.87
(1H, dd, J = 6.3, 11.2 Hz, C6HH), 4.01 (1H, t,
J = 9.3 Hz, C04H), 4.05 (1H, t, J = 7.8 Hz, C02H),
4.20 (1H, dd, J = 2.4, 11.2 Hz, C6HH), 4.26, 4.32 (each
1H, d, J = 11.7 Hz, ArCH2O), 4.40 (1H, ddd, J = 2.4,
6.3, 10.3 Hz, C5H), 4.58, 4.91 (each 1H, d, J = 10.8,
ArCH2O), 4.66 (1H, d, J = 7.8 Hz, C01H), 4.81, 5.11
(each 1H, d, J = 11.2, ArCH2O), 4.88, 5.01 (each 1H,
d, J = 10.3, ArCH2O), 5.28 (1H, d, J = 3.4 Hz, C1H),
5.53 (1H, dd, J = 3.4, 10.3 Hz, C2H), 5.88 (1H, t,
J = 10.2 Hz, C4H), 6.68 (1H, t, J = 10.3 Hz, C3H),
6.76–8.15 (31H, aromatic protons). 13C NMR (C6D6)
d 44.6, 54.7, 54.7, 54.7, 54.7, 55.4, 69.2, 69.8, 70.4,
71.3, 72.6, 73.0, 74.9, 75.1, 75.5, 81.6, 86.0, 86.2,
86.5, 97.4, 113.9, 113.9, 114.0, 114.1, 128.4, 128.5,
128.6, 128.8, 129.3, 129.5, 129.6, 129.7, 129.81,
129.88, 129.91, 130.6, 130.13, 130.16, 130.7, 131.6,
131.7, 131.9, 133.0, 133.18, 133.22, 159.5, 159.6,
159.7, 159.8, 165.7, 165.9, 166.2. FD-MS (%, rel int)
1165 (32, [M+H]+), 1164 (51, M+), 1044 (53,
[M+HÀMPM]+), 1043 (100, [MÀMPM]+). FD-HRMS
Found m/z = 1164.4142. Calcd for C66H68O17S: M+,
1164.4177.
1070, 1035 cmÀ1 1H NMR (C6D6) d 2.96 (3H, s,
.
C1OCH3), 3.28, 3.29, 3.30, 3.30, 3.31 (each 3H, s,
CH3O), 3.51 (1H, dd, J = 2.5, 9.7 Hz, C06HH), 3.63
(1H, br dt, J = 3.4, 9.3 Hz, C05H), 3.73 (1H, br d,
J = 11.3 Hz, C6HH), 3.84 (1H, dd, J = 2.9, 9.3 Hz,
C02H), 3.95 (1H, dd, J = 4.4, 9.7 Hz, C06HH), 4.01
(1H, t, J = 10.3 Hz, C04H), 4.10 (1H, br d, J = 9.8 Hz,
C5H), 4.13 (1H, t, J = 9.3 Hz, C03H), 4.19 (1H, dd,
J = 3.5, 11.3 Hz, C6HH), 4.24, 4.32 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.32, 4.58 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.49, 4.56 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.61, 5.01 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.80, 4.84 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.98 (1H, t, J = 9.8 Hz, C4H),
5.23 (1H, d, J = 3.4 Hz, C1H), 5.45 (1H, d, J = 2.9 Hz,
C01H), 5.54 (1H, dd, J = 3.4, 9.8 Hz, C2H), 6.65 (1H,
t, J = 9.8 Hz, C3H), 6.73–8.17 (30H, aromatic protons).
13C NMR (C6D6) d 42.1, 54.34, 54.38, 54.5, 54.6, 67.8,
69.0, 70.4, 71.8, 72.7, 72.9, 73.2, 73.3, 73.6, 75.1, 75.3,
79.4, 81.9, 83.0, 84.4, 97.0, 113.5, 113.6, 113.7, 113.8,
113.9, 128.1, 128.2, 129.1, 129.27, 129.31, 129.9, 130.2,
130.3, 130.51, 130.53, 131.4, 131.9, 132.68, 132.75,
159.1, 159.3, 159.38, 159.44, 159.5, 165.7, 165.8. FD-
MS (%, rel int) 1180 (28, M+), 1060 (79,
[M+HÀMPM]+), 1059 (72, [MÀMPM]+). FD-HRMS

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5133
Found m/z = 1180.4487. Calcd for C67H72O17S: M+,
1180.4490.
was filtered and the filtrate was concentrated in vacuo.
Without further purification, the residue was stirred with
DDQ (23.4 mg, 103 lmol) in a mixture of CH2Cl2
(1.5 mL) and H2O (150 lL) at room temperature for
20 h. Volatiles of the reaction mixture were removed un-
der reduced pressure. Purification of the residue by silica
gel column chromatography (MeOH/EtOAc 20:80)
afforded 47 (4.2 mg, 11.3 lmol, 88%, 2 steps). Since this
sample was soluble in only H2O, IR spectrum was not
4.21. Methyl 6-O-(deoxy-50-thio-b-D-glucopyranosyl)-a-
D-glucopyranoside (1)
A solution of b-27 (13.7 mg, 12.4 lmol) in MeOH
(2.0 mL) was stirred with NaOMe (5.0 mg) at room tem-
perature for 1 h. After DOWEX 50W (H+ form) was add-
ed until the solution was neutralized, the mixture was
filtered and the filtrate was concentrated in vacuo. The
residue was passed through a SepPak ODSꢂ to give 1
(4.6 mg, 12.4 lmol, 100%). Since this sample was soluble
25
1
measured. ½aꢀ +21ꢁ (c 0.09, H2O). H NMR (D2O) d
D
3.10 (1H, ddd, J = 3.4, 4.9, 10.3 Hz,C05H), 3.43 (3H, s,
CH3O), 3.49 (1H, dd, J = 8.8, 9.8 Hz, C4H), 3.57 (1H,
dd, J = 3.9, 9.8 Hz, C2H), 3.64 (1H, dd, J = 8.8,
10.3 Hz, C04H), 3.67 (1H, dd, J = 8.8, 9.8 Hz, C3H),
3.69 (1H, dd, J = 8.8, 9.3 Hz, C03H), 3.72 (1H, dd,
J = 2.0, 11.0 Hz, C6HH), 3.83 (1H, m, C5H), 3.85 (1H,
dd, J = 2.9, 9.3 Hz, C02H), 3.87 (1H, dd, 3.4, 11.4 Hz,
C60HH), 3.92 (1H, dd, J = 4.6, 11.2 Hz, C06HH), 4.13
(1H, dd, J = 4.6 Hz, 11.2 Hz, C6HH), 4.77 (1H,
J = 2.9 Hz, C10H), 4.82 (1H, d, J = 3.9 Hz, C1H). 13C
NMR (D2O) d 43.1, 55.3, 60.2, 66.6, 69.7, 70.2, 71.3,
73.5, 73.6, 74.2, 75.4, 81.9, 99.4. FAB-MS (negative
mode,%, rel int) 371 (21, [MÀH]À). FAB-HRMS (nega-
tive mode) Found m/z = 371.1000. Calcd for
C13H23O10S: ([MÀH]À), 371.1012.
in only H2O, IR spectrum was not measured. ½aꢀ22 +33ꢁ (c
D
0.29, H2O), 1H NMR (D2O) d 2.98 (1H, ddd, J = 3.4, 6.7,
9.8 Hz, C50H), 3.35 (1H, t, J = 9.3 Hz, C30H), 3.46 (3H, s,
CH3O), 3.51 (1H, t, J = 9.8 Hz, C4H), 3.58 (1H, dd,
J = 3.9, 9.8 Hz, C2H), 3.62 (1H, dd, J = 9.3, 9.8 Hz,
C40H), 3.693 (1H, t, J = 9.8 Hz, C3H), 3.696 (1H, t,
J = 9.3 Hz, C20H), 3.81 (1H, ddd, J = Hz, C5H), 3.87
(1H, dd, J = 6.4, 11.7 Hz, C60HH), 3.93 (1H, dd,
J = 4.9, 11.2 Hz, C6HH), 3.97 (1H, dd, J = 3.4, 11.7 Hz,
C60HH), 4.11 (1H, dd, J = 2.0, 11.2 Hz, C6HH), 4.68
(1H, d, J = 9.3 Hz, C10H), 4.82 (1H, d, J = 3.9 Hz,
C1H), 13C NMR (D2O) d 45.5, 55.5, 60.5, 69.5, 69.9,
70.7, 71.3, 73.1, 73.3, 76.7, 76.8, 83.4, 99.6, FAB-MS (neg-
ative mode, %, rel int) 371 (26, [MÀH]À), FAB-HRMS
(negative mode) Found m/z = 371.1017. Calcd for
C13H23O10S: [MÀH]À, 371.1012.
4.24. Methyl 4-O-(50-deoxy-50-thio-a-D-glucopyranosyl)-
a-D-glucopyranoside (48)
A solution of 43 (22.0 mg, 18.6 lmol) in a mixture of
MeOH (2.5 mL) and 1 M NaOH aqueous solution
(300 lL) was stirred vigorously at room temperature
for 1.5 h. The reaction mixture was poured into brine
and extracted with CHCl3 (·4). The organic extracts
were combined, dried over MgSO4, and concentrated
in vacuo. After the residue was diluted in a mixture of
CH2Cl2 (2.5 mL) it was and H2O (250 lL) stirred with
DDQ (30.0 mg, 132 lmol) for 16 h. To the mixture,
H2O (3.0 mL) and MeOH (10 mL) were added and the
mixture was stirred with a catalytic amount of concd
HCl for an additional 30 min. The solution was concen-
trated under reduced pressure. Purification of the resi-
due by silica gel chromatography (MeOH/EtOAc
15:85) gave 48 (5.3 mg, 14.2 lmol, 77%, 2 steps). Since
4.22. 4-Nitrophenyl 6-O-(50-deoxy-50-thio-b-D-gluco-
pyranosyl)-a-D-glucopyranoside (46)
A solution of b-28 (20.5 mg, 17.0 lmol) in MeOH
(2.0 mL) was stirred with NaOMe (5.0 mg) at room tem-
perature for 1 h. After DOWEX 50W (H+ form) was
added until the solution was neutralized, the mixture
was filtered and the filtrate was concentrated in vacuo.
The residue was passed through a SepPak ODSꢂ to give
46 (6.5 mg, 13.5 lmol, 79%). Since this sample was solu-
26
D
ble in only H2O, IR spectrum was not measured. ½aꢀ
1
+31ꢁ (c 0.67, H2O). H NMR (D2O) d 2.87 (1H, ddd,
J = 3.4, 5.8, 10.2 Hz, C50H), 3.27 (1H, t, J = 8.8 Hz,
C30H), 3.51 (1H, dd, J = 8.8, 10.2 Hz, C40H), 3.58 (1H,
t, J = 8.8 Hz, C20H), 3.59 (1H, t, J = 8.8 Hz, C4H),
3.76 (1H, dd, J = 5.8, 11.7 Hz, C60HH), 3.83 (1H, dd,
J = 3.4, 9.8 Hz, C2H), 3.85 (1H, dd, J = 3.4, 11.7 Hz,
C60HH), 3.88–4.02 (4H, C3H, C5H, C6H2), 4.56 (1H,
d, J = 8.8 Hz, C10H) 5.87 (1H, d, J = 3.4 Hz, C1H),
7.33, 8.30 (each 2H, d, J = 9.3 Hz, aromatic protons),
13C NMR (D2O) d 46.2, 61.2, 70.2, 71.1, 71.8, 72.7,
73.8, 72.9, 77.4, 77.7, 84.1, 97.3, 117.8, 127.0, FAB-MS
(negative mode, %, rel int) 479 (3.9, MÀ), 478 (2.3,
[MÀH]À), FAB-HRMS (negative mode) Found
m/z = 479.1115. Calcd for C18H25O12NS: MÀ, 479.1097.
this sample was soluble in only H2O, IR spectrum was
27
not measured. ½aꢀ + 28ꢁ (c 0.08, H2O). 1H NMR
D
(D2O, 38 ꢁC d 3.05 (1H, dt, J = 4.9, 9.3 Hz, C05H),
3.42 (3H, s, C1OCH3), 3.59 (1H, dd, J = 3.9, 9.7 Hz,
C2H), 3.62–3.67 (2H, C03H, C04H), 3.73–3.77 (2H,
C4H, C5H), 3.82–3.85 (2H, C02H, C6HH), 3.88–3.90
(3H, C06H2, C6HH), 3.95 (1H, t, J = 9.7 Hz, C3H),
4.81 (1H, d, J = 3.9 Hz, C1H), 5.33 (1H, d, J = 3.4 Hz,
C01H). 13C NMR (D2O, 38 ꢁ) d 43.9, 55.2, 60.2, 61.0,
70.2, 71.3, 73.4, 73.9, 74.1, 75.5, 75.6, 82.8, 99.2. FAB-
MS (negative mode, %, rel int) 371 (100, [MÀH]À).
FAB-HRMS (negative mode) Found m/z = 371.0975.
Calcd for C13H23O10S: ([MÀH]À), 371.1012.
4.23. Methyl 6-O-(50-deoxy-50-thio-a-D-glucopyranosyl)-
a-D-glucopyranoside (47)
4.25. Tetrahydropyranyl 6-O-triphenylmethyl-5-deoxy-5-
thio-a-D-glucopyranoside (50a)
A solution of 41 (15.0 mg, 12.9 lmol) in MeOH (1.0 mL)
was stirred with NaOMe (3.5 mg, 64.4 lmol) at room
temperature for 1 h. After DOWEX 50W (H+ form)
was added until the solution was neutralized, the mixture
A solution of 6a (369 mg, 1.42 mmol) in pyridine
(3.5 mL) was stirred with TrCl (607 mg, 2.16 mmol)

5134
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
and DMAP (17 mg, 142 lmol) at room temperature for
24 h. The mixture was concentrated under reduced pres-
sure, diluted with water, and extracted with EtOAc (·3).
The organic extracts were washed with brine, dried over
MgSO4, respectively, and concentrated in vacuo. Purifi-
cation of the residue by silica gel column chromatog-
raphy (acetone/CH2Cl2 20:80) gave 50a (589 mg,
was stirred at room temperature. After stirring for
40 min, additional NaH (110 mg) and MPMBr
(200 lL) were added into the mixture and the resulting
mixture was stirred for further additional 12 h. The ex-
cess reagents were decomposed by the addition of
MeOH (ca. 1.0 mL) and Et3N (ca. 1.0 mL). After stir-
ring for an additional 30 min, the mixture was poured
into water and extracted with Et2O (·3). The combined
ethereal extracts were washed with brine and dried over
MgSO4. Purification of the residue by silica gel column
chromatography (EtOAc/benzene 4:96) afforded 51b
(167 mg, 191 lmol, 62%) as a syrup. The 1H NMR spec-
trum of this sample indicated that the sample consists of
a mixture of diastereomers due to the asymmetric center
in the EE group (50:50). IR (film) 2935, 1615, 1585,
1
1.14 lmol, 80%) as a syrup. The H NMR spectrum of
this sample indicated that the sample consists of a dia-
stereomeric mixture due to the asymmetric center in
the THP group (50:50). IR (film) 3410, 2930, 1445,
1120, 1070, 1020, 970, 755, 700 cmÀ1. 1H NMR (CDCl3,
some signals could not be assigned due to signals over-
lapping.) d 1.50–1.83 (6H, C30H2, C40H2, C50H2), 3.06
(1H · 0.5, dt, J = 4.9, 9.3 Hz, C5H), 3.35 (1H · 0.5,
dd, J = 4.9, 10.2, C6HH), 3.49 (1H · 0.5, dd, J = 4.9,
10.2 Hz, C6HH), 3.55 (1H · 0.5, C6HH), 3.66
(1H · 0.5, t, J = 9.3 Hz, C3H), 3.67 (1H · 0.5, t,
J = 9.3 Hz, C3H), 3.80 (1H · 0.5, dd, J = 3.4, 9.8 Hz,
C2H), 3.82 (1H · 0.5, t, J = 10.2 Hz, C4H), 3.85
(1H · 0.5, dd, J = 3.4, 9.3 Hz, C2H), 4.02 (1H · 0.5,
C60HH), 4.83 (1H · 0.5, d, J = 3.4 Hz, C1H), 4.92
(1H · 0.5, br t, J = 3.4 Hz, C20H), 4.96 (1H · 0.5, br,
C20H), 4.97 (1H · 0.5, d, J = 3.4 Hz, C1H). FD-MS
(%, rel int) 552 (100, M+), 243 (53, Ph3P+). FD-HRMS
Found m/z = 522.2072. Calcd for C30H34O6S: M+,
522.2076.
1515, 1250, 1175, 1140, 1035, 760 cmÀ1 1H NMR
.
(C6D6) d 1.13, 1.18 (each 3H · 0.5, t, CH3CH2OCH-
(CH3)O), 1.35, 1.44 (each 3H · 0.5, d, J = 5.4 Hz,
(EtOCH(CH3)O), 3.288, 3.290, 3.294, 3.294, 3.32, 3.32
(each 3H · 0.5, s, CH3O), 3.50–3.66 (5H · 0.5, C5H,
C6HH, CH3CHHOCH(CH3)O · 3), 3.71–3.75 (3H ·
0.5, C6HH · 2, C5H), 3.79 (1H · 0.5, C6HH), 3.94–
4.06 (4H · 0.5, C2H · 2, C4H, CH3CHHOCH(CH3)O),
4.11–4.24 (3H · 0.5, C3H · 2, C4H), 4.36, 4.88 (each
1H · 0.5, d, J = 10.2 Hz, ArCH2O), 4.39, 4.91 (each
1H · 0.5, d, J = 10.7 Hz, ArCH2O), 4.49, 4.56
(each 1H · 0.5, d, J = 11.2 Hz, ArCH2O), 4.56, 4.59
(each 1H · 0.5, d, J = 11.3 Hz, ArCH2O), 4.82, 5.00
(each 1H · 0.5, d, J = 10.7 Hz, ArCH2O), 4.84, 5.03
(each 1H · 0.5, d, J = 10.7 Hz, ArCH2O), 4.71, 5.13
(each 1H · 0.5, d, J = 2.9 Hz, C1H), 4.91, 5.18
(1H · 0.5, q, J = 4.9 Hz, EtOCH(CH3)O). FD-MS (%,
rel int) 870 (8, M+), 243 (100, Ph3C+). FD-HRMS
Found m/z = 870.3820. Calcd for C53H58O9S: [M+],
870.3802.
4.26. Ethoxyethyl 6-O-triphenylmethyl-5-deoxy-5-thio-a-
D-glucopyranoside (50b)
A solution of the tetraol 6b (122 mg, 453 lmol) in pyri-
dine (1.0 mL) was stirred with TrCl (703 mg, 2.52 mmol)
and DMAP (3.0 mg, 24 lmol) at room temperature for
16 h. After the mixture was concentrated in vacuo, puri-
fication of the residue by silica gel column chromatog-
raphy (acetone/CH2Cl2 20:80) gave 50b (186 mg,
365 lmol, 81%) as a pale yellow oil. The 1H NMR spec-
trum of this sample indicated that the sample consists of
a diastereomeric mixture due to the asymmetric center in
the EE group (50:50). IR (film) 3420, 2980, 2930, 1450,
4.28. 2,3,4-Tris-O-(4-methoxyphenyl)methyl-6-O-triphenyl-
methyl-5-deoxy-5-thio-a-D-glucopyranose (52)
4.28.1. Preparation from 51a. A solution of 51a
(400 mg, 454 lmol) in EtOH (90 mL) was stirred with
p-TsOH (43.4 mg, 228 lmol) at room temperature for
7 h. The mixture was neutralized with Et3N and con-
centrated in vacuo. Purification of the residue by silica
gel column chromatography (EtOAc/hexane 30:70)
afforded 52 (51.9 mg, 74.0 lmol, 16%) as a colorless
1
1075, 950, 760, 710 cmÀ1. H NMR (CDCl3, some sig-
nals could not be assigned due to signals overlapping.)
d 1.21, 1.22 (each 3H · 0.5, t, J = 7.2 Hz, CH3CH2),
1.35, 1.38 (each 3H · 0.5, d, J = 5.4 Hz, EtOCH(-
CH3)O), 2.56, 2.72 (each 1H · 0.5, br, OH), 2.90
(2H · 0.5, br, OH · 2), 2.95 (2H · 0.5, br, OH · 2),
3.08, 3.26 (each 1H · 0.5, dt, J = 4.9, 10.3 Hz, C5H),
3.37–3.87 (14H · 0.5), 4.65 (1H · 0.5, d, J = 3.4 Hz,
C1H), 4.93 (1H · 0.5, d, J = 2.9 Hz, C1H), 4.95, 5.03
(1H · 0.5, q, J = 5.4 Hz, EtOCH(Me)O), EI-MS (%,
rel int) 510 (0.3, M+), 243 (100, Ph3C+). EI-HRMS
Found m/z = 510.2081. Calcd for C29H34O6S: [M+],
510.2076.
syrup. The yield was 33% according to the recovery
26
D
2930, 1610, 1510, 1245, 1175, 1090, 1065, 1030,
of 51a. ½aꢀ +5.4ꢁ (c 1.00, CHCl3). IR (film) 3410,
755 cmÀ1 1H NMR (C6D6) d 2.48 (1H, br, C1OH),
.
3.29, 3.30, 3.32 (each 3H, s, CH3O), 3.64–3.70 (3H,
C5H, C6H2), 3.85 (1H, dd, J = 2.9, 9.3 Hz, C2H),
3.97 (1H, t, J = 8.8 Hz, C3H), 4.05 (1H, t, J = 8.8 Hz,
C4H), 4.35, 4.82 (each 1H, d, J = 10.7 Hz, ArCH2O),
4.38, 4.46 (each 1H, d, J = 10.7 Hz, ArCH2O), 4.79
(1H, br, C1H), 4.83, 4.92 (each 1H, d, J = 10.7 Hz,
ArCH2O), 6.70–7.64 (27H, aromatic protons). 13C
NMR (C6D6) d 42.4, 54.7, 61.9, 71.8, 72.4, 74.9, 75.9,
82.4, 83.4, 85.0, 87.1, 113.7, 113.9, 114.1, 127.3,
128.1, 129.3, 129.39, 129.41, 129.7, 144.3, 159.4,
159.5, 159.8. FD-MS (%, rel int) 798 (34, M+). FD-
HRMS Found m/z = 798.3229. Calcd for C49H50O8S:
[M+], 798.3226.
4.27. Ethoxyethyl 2,3,4-[tris-O-(4-methoxyphenyl)meth-
yl]-6-O-triphenylmethyl-5-thio-a-D-glucopyranoside (51b)
A solution of 50b (158 mg, 310 lmol) was added to a
suspension of freshly washed NaH (80.0 mg, 3.33 mmol)
that was added to a solution of DMF (3.0 mL) at room
temperature. After 10 min, MPMBr (ca. 50% in toluene,
400 lL, ca. 1.6 mmol) was added to the mixture and it

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5135
1
4.28.2. Preparation from 51b. A solution of 51b (9.5 mg,
10.9 lmol) in a mixture of EtOH (700 lL) and PrOH
(250 lL) was stirred with PPTS (10.0 mg, 42.7 lmol) at
room temperature for 2.5 h. After concentration in vac-
uo, the residue was diluted again with EtOH (1.0 mL)
and then the mixture was stirred for 1 h. After concen-
tration, purification of the residue by silica gel column
chromatography (EtOAc/hexane 25:75) gave 52
710 cmÀ1. H NMR (C6D6) d 3.11 (3H, s, C1OCH3),
3.31, 3.32, 3.34 (each 3H, s, CH3O), 3.46 (1H, dt,
J = 2.4, 3.9, 10.3 Hz, C05H), 3.53 (1H, dd, J = 2.9,
9.3 Hz, C06HH), 3.58 (1H, dd, J = 2.0, 11.2 Hz,
C6HH), 3.67 (1H, dd, J = 3.9, 9.3 Hz, C06HH), 4.04
(1H, dd, J = 2.9, 9.3 Hz, C02H), 4.14 (1H, dd, J = 4.9,
11.2 Hz, C6HH), 4.17 (1H, dd, J = 9.3, 10.3 Hz,
C04H), 4.25 (1H, t, J = 9.3 Hz, C03H), 4.35 (1H, ddd,
J = 2.0, 4.9, 9.8 Hz, C5H), 4.42, 4.94 (each 1H, d,
J = 10.3 Hz, ArCH2O), 4.53, 4.65 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.60 (1H, d, J = 2.9 Hz, C01H),
4.89, 5.05 (each 1H, d, J = 10.8 Hz, ArCH2O), 5.30
(1H, d, J = 3.4 Hz, C1H), 5.44 (1H, dd, J = 3.4,
10.3 Hz, C2H), 6.05 (1H, t, J = 9.8 Hz, C4H), 6.62
(1H, dd, J = 9.8, 10.3 Hz, C3H), 6.70–8.13 (42H, aro-
matic protons). 13C NMR (C6D6) d 42.2, 54.71, 54.75,
55.2, 61.8, 67.7, 69.3, 70.0, 71.5, 72.6, 72.7, 75.0, 76.0,
81.4, 82.4, 83.6, 85.2, 87.0, 97.5, 113.7, 113.9, 114.2,
127.3, 128.1, 128.4, 128.47, 128.53, 129.3, 129.4, 129.6,
129.7, 129.8, 129.9, 130.10, 130.14, 131.4, 131.6, 132.3,
132.9, 133.1, 133.2, 144.3, 159.4, 159.5, 159.8, 165.4,
165.8, 166.3. FD-MS (%, rel int) 1285 (15, [MÀH]+),
1286 (14, M+), 1287 (10, [M+H]+). FD-HRMS Found
m/z = 1286.4717. Calcd for C77H74O16S: [M+],
1286.4698.
1
(8.0 mg, 10.0 lmol, 92%) as a colorless syrup. The H
NMR and 13C NMR spectra of this sample were identi-
cal with those prepared from 51a.
4.29. 2,3,4-[Tris-O-(4-methoxyphenyl)methyl-6-O-triphe-
nylmethyl]-5-deoxy-5-thio-a-D-glucopyranosyl trichloro-
acetimidate (53)
According to general procedure A, a solution of 52
(139 mg, 174 lmol) in CH2Cl2 (4.0 mL) was stirred with
CCl3CN (260 lL, 2.61 mmol) in the presence of catalytic
DBU (3.7 lL, 24.9 lmol, 0.14 equiv) at 0 ꢁC for 40 min.
After the mixture was diluted with benzene, the volatiles
were completely removed in vacuo. Purification of the
residue by silica gel chromatography (EtOAc/hexane
15:85) gave 53 (135 mg, 143 lmol, 82%) as a colorless
1
syrup. H NMR (CDCl3) d 3.43 (1H, ddd, J = 2.4, 3.9,
10.3 Hz, C5H), 3.54 (1H, dd, J = 2.4, 9.8 Hz, C6HH),
3.58 (1H, dd, J = 3.9, 9.8 Hz, C6HH), 3.76, 3.78, 3.79
(each 3H, s, CH3O), 3.88 (1H, t, J = 9.3 Hz, C3H),
3.97 (1H, dd, J = 9.3. 9.8 Hz, C4H), 3.99 (1H, dd,
J = 2.9, 9.3 Hz, C2H), 4.22, 4.63 (each 1H, d,
J = 10.3 Hz, ArCH2O), 4.61, 4.72 (each 1H, d,
J = 11.3 Hz, ArCH2O), 4.67, 4.79 (each 1H, d,
J = 10.3 Hz, ArCH2O), 6.38 (1H, d, J = 2.9 Hz, C1H),
6.81, 6.85 (each 2H, J = 8.8 Hz, aromatic protons),
7.18-7.43 (23H, aromatic protons), 8.61 (1H, s,
C( = NH)CCl3). 13C NMR (CDCl3) d 43.4, 55.2, 61.0,
72.0, 75.1, 75.0, 76.4, 80.9, 82.6, 83.4, 86.5, 91.2, 113.5,
113.69, 113.73, 127.1, 127.8, 128.3, 128.9, 129.2, 129.6,
129.7, 130.16, 130.21, 130.9, 143.4, 159.06, 159.11,
159.16, 161.2. This sample was immediately used for
the next glycosylation step.
26
D
4.30.2. Physical data for b-54. ½aꢀ +29ꢁ (c 0.41, CHCl3).
IR (film) 2935, 1735, 1515, 1250, 1095, 1070, 1035, 755,
710 cmÀ1. 1H NMR (C6D6) d 2.84 (1H, ddd, J = 3.9, 4.9,
9.8 Hz, C05H), 3.14 (3H, s, C1OCH3), 3.30 3.31, 3.31
(each 3H, s, CH3O), 3.50 (1H, t, J = 8.3 Hz, C03H),
3.61 (1H, dd, J = 4.9, 9.3 Hz, C06HH), 3.67 (1H, dd,
J = 3.4, 9.3 Hz, C06HH), 3.90 (1H, dd, J = 6.8, 9.8 Hz,
C6HH), 4.04 (1H, dd, J = 8.3, 9.8 Hz, C04H), 4.06
(1H, t, J = 8.3 Hz, C02H), 4.20 (1H, dd, J = 2.0,
10.8 Hz, C6HH), 4.33, 4.79 (each 1H, d, J = 10.3 Hz,
ArCH2O), 4.45 (1H, ddd, J = 2.0, 6.8, 9.8 Hz, C5H),
4.65 (1H, d, J = 8.3 Hz, C01H), 4.82, 4.98 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.82, 5.13 (each 1H, d,
J = 10.7 Hz, ArCH2O), 5.28 (1H, d, J = 3.4 Hz, C1H),
5.54 (1H, dd, J = 3.4, 10.3 Hz, C2H), 5.83 (1H, dd,
J = 9.8, 10.3 Hz, C4H), 6.70 (1H, t, J = 10.3 Hz, C3H),
6.70–8.17 (42H, aromatic protons). 13C NMR (C6D6) d
44.8, 54.7, 54.7, 54.7, 55.4, 62.7, 69.8, 70.1, 70.5, 71.2,
72.6, 74.8, 75.3, 75.7, 81.7, 85.8, 86.3, 86.5, 87.2, 97.4,
113.7, 113.9, 114.0, 127.3, 127.9, 128.1, 128.4, 128.52,
128.54, 128.60, 129.27, 129.30, 129.51, 129.55, 129.7,
129.8, 129.9, 130.0, 130.1, 130.2, 131.3, 131.7, 131.9,
133.0, 133.21, 133.24, 144.3, 159.50, 159.51, 159.7,
165.7, 165.9, 166.2. FD-MS (%, rel int) 1285 (25,
[MÀH]+), 1286 (34, M+), 1287 (25, [M+H]+). FD-
4.30. Methyl 6-[20,30,40-tris-O-(4-methoxyphenyl)methyl-
60-O-(triphenyl)methyl-50-deoxy-50-thio-a-D-glucopyrano-
syl]-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (54)
According to general procedure B, a suspension of 53
(46.3 mg, 49.1 lmol) and 16a (27.1 mg, 53.5 lmol) in
CH2Cl2 (3.0 mL) was stirred in the presence of pow-
dered MS4A (102 mg) for 1 h at room temperature un-
der N2 atmosphere. After the mixture was cooled to
À78 ꢁC, TESOTf (210 lmol/mL solution in CH2Cl2,
23.3 lL, 0.05 equiv) was added to the suspension. After
stirring for 2 h at the same temperature, pyridine was
added to the mixture and the mixture was filtered
through silica gel pad and then concentrated in vacuo.
Purification of the residue by silica gel chromatography
(Et2O/benzene 2:98) and subsequent preparative TLC
afforded 54 (42.0 mg, 32.6 lmol, 67%) and the b-isomer
(4.6 mg, 3.6 lmol, 7%) as a colorless syrup (a:b = 90:10).
HRMS
Found
m/z = 1286.4706.
Calcd
for
C77H74O16S: [M+], 1286.4698.
4.31. Methyl 6-O-[20,30,40-[tris-O-(4-methoxyphe-
nyl)methyl]-50-deoxy-50-thio-a-D-glucopyranosyl]2,3,4-
tri-O-benzoyl-a-D-glucopyranoside (55)
A solution of 54 (57.3 mg, 44.5 lmol) in a mixture of
MeOH (2.0 mL) and THF (400 lL) was stirred with p-
TsOH (1.0 mg, 5.26 lmol) at room temperature for
5 h. After the addition of Et3N (20 lL), the mixture
was concentrated in vacuo. Purification of the residue
26
4.30.1. Physical data for a-54. ½aꢀ +59ꢁ (c 1.10, CHCl3).
D
IR (film) 2935, 1735, 1515, 1250, 1095, 1070, 1035, 755,

5136
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
by silica gel chromatography (EtOAc/hexane 35:65)
gave 55 (33.0 mg, 31.6 lmol, 71%) as a colorless oil.
4.69 (1H, d, J = 2.9 Hz, C001H), 4.88, 5.08 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.91, 5.20 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.94, 5.08 (each 1H, d,
J = 10.7 Hz, ArCH2O), 5.33 (1H, d, J = 3.9 Hz, C1H),
5.46 (1H, dd, J = 3.9, 9.8 Hz, C2H), 6.07 (1H, t,
J = 9.8 Hz, C4H), 6.64 (1H, t, J = 9.8 Hz, C3H), 6.67–
8.13 (54H, aromatic protons). 13C NMR (C6D6) d 41.6,
54.66, 54.66, 54.70, 54.70, 54.76, 54.76 55.3, 61.8, 67.7,
67.8, 69.4, 70.0, 71.4, 72.1, 72.5, 72.8, 75.1, 75.4, 75.96,
75.99, 80.9, 81.4, 82.2, 82.6, 83.5, 83.6, 85.2, 85.4, 87.0,
97.5, 113.6, 113.9, 114.0, 114.1, 127.2, 127.9, 128.1,
128.3, 128.46, 128.51, 128.6, 129.3, 129.48, 129.51,
129.56, 129.60, 129.7, 129.9, 130.1, 130.2, 131.4, 131.8,
132.2, 132.9, 133.1, 133.2, 144.3, 159.36, 159.43,
159.67, 159.71, 165.4, 165.8, 166.2. ESI-MS (%, rel int)
1824 (82, [M+Na]+), 1863 (21, [M+K]+). ESI-HRMS
Found m/z = 1847.6650. Calcd for C107H108O23S2Na:
[M+Na]+, 1847.6621.
26
½aꢀ +93ꢁ (c 0.60, CHCl3). IR (film): 3520, 2935, 1735,
D
1615, 1515, 1455, 1280, 1250, 1175, 1095, 1035,
710 cmÀ1 1H NMR (C6D6) d 1.45 (1H, dd, J = 3.9,
.
7.8 Hz, C06OH), 3.11 (3H, s, C1OCH3), 3.27, 3.29,
3.32 (each 3H, s, CH3O), 3.39 (1H, dt, J = 3.9,
10.8 Hz, C05H), 3.53 (1H, dd, J = 2.0, 11.3 Hz,
C6HH), 3.61 (1H, dt, J = 3.9, 11.2 Hz, C06HH), 3.84–
3.91 (3H, C02H, C03H, C06HH), 4.08 (1H, dd, J = 4.9,
11.3 Hz, C6HH), 4.30 (1H, t, J = 9.3 Hz, C40H), 4.32
(1H, ddd, J = 2.0, 4.9, 10.3 Hz, C5H), 4.51 (1H, d,
J = 2.9 Hz, C01H), 4.54, 4.59 (each 1H, d, J = 11.7 Hz,
ArCH2O), 4.70, 5.05 (each 1H, d, J = 10.7 Hz,
ArCH2O), 4.91, 5.07 (each 1H, d, J = 10.7 Hz,
ArCH2O), 5.32 (1H, d, J = 3.4 Hz, C1H), 5.45 (1H,
dd, J = 3.4, 10.3 Hz, C2H), 6.09 (1H, t, J = 10.3 Hz,
C4H), 6.45 (1H, t, J = 10.3 Hz, C3H), 6.74–8.15 (27H,
aromatic protons). 13C NMR (C6D6) d 43.5, 54.71,
54.72, 54.75, 55.3, 62.3, 67.6, 69.3, 69.9, 71.4, 72.4,
75.4, 75.9, 72.8, 81.3, 83.1, 83.4, 85.1, 97.5, 113.9,
114.12, 114.21, 127.9, 128.1, 128.35, 128.43, 128.5,
128.6, 129.6, 129.7, 129.8, 129.9, 130.0, 130.2, 131.4,
132.2, 132.9, 133.17, 133.22, 159.5, 159.7, 159.8, 165.5,
165.8, 166.3. FD-MS (%, rel int) 1044 (33, M+). FD-
4.33. Methyl 6-O-[[60-O-[200,300,400-[tris-O-(4-methoxyphe-
nyl)methyl]-500-deoxy-500-thio-a-D-glucopyranosyl]-
20,30,40-[tris-O-(4-methoxyphenyl)methyl]-50-deoxy-
50-thio-a-D-glucopyranosyl]]-2,3,4-tris-O-benzoyl-a-
D-glucopyranoside (57)
HRMS
Found
m/z = 1044.3584.
Calcd
for
A solution of 56 (30.5 mg, 16.7 lmol) in a mixture of
MeOH (2.5 mL) and THF (800 lL) was stirred with p-
TsOH (1.0 mg, 5.26 lmol) for 3 h. The mixture was neu-
tralized with Et3N and concentrated under reduced pres-
sure. Purification of the residue by silica gel column
chromatography (EtOAc/hexane 35:65) afforded 57
C58H60O16S: [M+], 1044.3602.
4.32. Methyl 6-O-[[60-O-[200,300,400-[tris-O-(4-methoxyphe-
nyl)methyl]-600-O-triphenylmethyl-500-deoxy-500-thio-a-D-
glucopyranosyl]-20,30,40-[tris-O-(4-methoxyphenyl)meth-
yl]-50-deoxy-50-thio-a-D-glucopyranosyl]]-2,3,4-tri-O-
benzoyl-a-D-glucopyranoside (56)
(17.7 mg, 11.2 lmol, 67%) as a colorless syrup. The yield
23
D
CHCl3). IR (film) 3470, 1730, 1610, 1510, 1285, 1250,
was 78% according to recovery of 56. ½aꢀ +121ꢁ (c 1.60,
1
According to general procedure B, a mixture of 55
(39.0 mg, 41.3 lmol) and 53 (40.2 mg, 38.5 lmol) in
CH2Cl2 (2.7 mL) was stirred in the presence of pow-
dered MS4A (152 mg) for 1 h at room temperature
and N2 atmosphere. After the mixture was cooled to
À78 ꢁC, TESOTf (210 lmol/L solution in CH2Cl2,
9.8 lL, 0.05 equiv) was added to the suspension. After
stirring for 2 h at the same temperature, pyridine was
added into the mixture and the resulting mixture was
passed through silica gel pad and then concentrated in
vacuo. Purification of the residue by silica gel chromat-
ography (Et2O/benzene 5:95) afforded 56 (35.1 mg,
19.2 lmol, 47%) as a colorless syrup after removal of
1095, 1065, 1035 cmÀ1. H NMR (C6D6) d 1.44 (1H,
br, C006OH), 3.16 (3H, s, C1OCH3), 3.25, 3.29, 3.29,
3.31, 3.31, 3.33 (each 3H, s, CH3O), 3.34 (1H, C005H),
3.53–3.59 (2H, C05H, C06HH), 3.64 (2H, dd, J = 2.0,
11.2 Hz, C6HH, C600HH), 3.86–3.92 (4H, C02H, C002H,
C004H, C006HH), 4.08 (1H, dd, J = 9.3, 10.7 Hz, C04H),
4.13 (1H, dd, J = 4.9, 11.2 Hz, C6HH), 4.26 (1H, t,
J = 9.3 Hz, C003H), 4.32 (1H, t, J = 9.3 Hz, C03H), 4.35
(1H, ddd, J = 2.0, 4.9, 10.3 Hz, C5H), 4.40 (1H, dd,
J = 4.4, 11.2 Hz, C06HH), 4.50 (1H, d, J = 3.4 Hz,
C01H), 4.51, 4.58 (each 1H, d, J = 10.7 Hz, ArCH2O),
4.52, 4.66 (each 1H, d, J = 11.7 Hz, ArCH2O), 4.60
(1H, d, J = 2.9 Hz, C001H), 4.69, 5.03 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.91, 5.12 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.93, 5.24 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.96, 5.09 (each 1H, d,
J = 10.7 Hz, ArCH2O), 5.34 (1H, d, J = 3.4 Hz, C1H),
5.48 (1H, dd, J = 3.4, 10.2 Hz, C2H), 6.06 (1H, t,
J = 10.3 Hz, C4H), 6.64 (1H, t, J = 10.2 Hz, C3H),
6.72–8.14 (39H, aromatic protons). 13C NMR (C6D6) d
41.5, 43.9, 54.69, 54.69, 54.72, 54.72, 54.75, 54.77,
55.3, 62.2, 67.7, 69.4, 70.0, 71.4, 72.0, 72.6, 75.43,
75.45, 75.9, 76.0, 72.8, 80.7, 81.4, 82.6, 82.8, 83.4, 83.5,
85.2, 85.3, 97.5, 113.92, 113.93, 114.06, 114.11, 114.17,
127.9, 128.1, 128.4, 128.5, 128.6, 129.4, 129.5, 129.61,
129.63, 129.7, 129.8, 129.95, 130.00, 130.16, 130.20,
131.3, 131.4, 131.8, 132.0, 132.2, 132.9, 133.2, 133.3,
159.5, 159.72, 159.75, 165.4, 165.9, 166.3. FD-MS (%,
rel int) 1583 (22, [M+H]+), 1582 (23, M+), 1462 (70,
acetoamide by silica gel column chromatography
25
D
(film) 2935, 1735, 1615, 1515, 1250, 1175, 1095, 1070,
(EtOAc/hexane 27:73). ½aꢀ +96ꢁ (c 0.57, CHCl3). IR
1035, 760, 710 cmÀ1. H NMR (C6D6) d 3.15 (3H, s,
1
C1OCH3), 3.28, 3.29, 3.29, 3.30, 3.31, 3.34 (each 3H,
s, CH3O), 3.50–3.71 (6H, C005H, C05H, C6HH, C006H2,
C06HH), 3.88 (1H, dd, J = 2.9, 9.8 Hz, C02H), 4.04
(1H, dd, J = 2.9, 9.3 Hz, C002H), 4.10 (1H, dd, J = 8.8,
10.3, C04H), 4.11 (1H, dd, J = 4.9, 10.7 Hz, C6H), 4.18
(1H, dd, J = 8.8, 10.2 Hz, C004H), 4.24 (1H, dd,
J = 8.8, 9.3 Hz, C003H), 4.30 (1H, dd, J = 8.8, 9.3 Hz,
C03H), 4.34 (1H, ddd, J = 2.4, 4.9, 9.8 Hz, C5H), 4.38,
4.92 (each 1H, d, J = 10.7 Hz, ArCH2O), 4.44 (1H, dd,
J = 4.4, 10.3 Hz, C06HH), 4.493, 4.57 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.496 (1H, d, J = 2.9 Hz,
C01H), 4.56, 4.67 (each 1H, d, J = 11.3 Hz, ArCH2O),

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5137
[MÀMPM+H]+), 121 (100, MPM+). FD-HRMS Found
m/z = 1582.5651. Calcd for C88H94O23S2: [M+],
1582.5627.
2265 (100, [M+Na]+). ESI-HRMS Found m/z =
2263.8147. Calcd for C126H136NaO31S3: [M+Na]+,
2263.8125.
4.34. Methyl 6-O-[[[60-O-[[600-O-[2000,3000,4000,6000-[tetrakis-
O-(4-methoxyphenyl)methyl]-5000-deoxy 5000-thio-a-D-
glucopyranosyl]-200,300,400-[tris-O-(4-methoxyphenyl)meth-
yl]-500-deoxy-500-thio-a-D glucopyranosyl]]-20,30,40-[tris-O-
(4-methoxyphenyl) methyl]-50-deoxy-50-thio-a-D-gluco-
pyranosyl]]]-2,3,4-tri-O-benzoyl-a-D-glucopyranoside (58)
4.35. Methyl 6-O-[[60-O-[600-O-(5000-deoxy-5000-thio-a-D-
glucopyranosyl)-500-deoxy-500-thio-a-D-glucopyranosyl]50-
deoxy-50-thio-a-D-glucopyranosyl]]-a-D-glucopyranoside
(2)
A solution of 58 (11.5 mg, 5.10 lmol) in MeOH
(2.0 mL) was stirred with NaOMe (2.5 mg, 46.3 lmol)
at room temperature for 1 h. After DOWEX 50W (H+
form) was added until the solution indicated neutral,
the mixture was filtered and the filtrate was concentrated
in vacuo. Without further purification, the residue was
stirred with DDQ (46.2 mg, 204 lmol) in a mixture of
CH2Cl2 (1.0 mL) and H2O (100 lL) at room tempera-
ture for 12 h. Volatiles of the reaction mixture were re-
moved under reduced pressure. Purification of the
residue by silica gel column chromatography (MeOH/
EtOAc 40:60) afforded 2 (2.4 mg, 3.29 lmol, 65%, 2
According to general procedure B, a suspension of 15
(8.0 mg, 9.70 lmol) and 57 (17.5 mg, 11.0 lmol) in
CH2Cl2 (700 lL) was stirred with MS4A (102 mg) at
room temperature for 20 min. After the mixture was
cooled to À78 ꢁC, TESOTf (210 lmol/mL solution in
CH2Cl2, 2.3 lL, 0.05 equiv) was added to the suspen-
sion. After stirring for 1 h at À78 ꢁC, pyridine was add-
ed and the mixture was filtered through a pad of silica
gel, and the pad was washed with EtOAc. After concen-
tration in vacuo, purification of the residue by silica gel
column chromatography (Et2O/benzene 5:95) gave 58
(14.6 mg, 67%) as a colorless syrup. ½aꢀ +115ꢁ (c 0.28,
steps). Since this sample was soluble in only H2O, IR
25
D
CHCl3). IR (film) 2960, 2930, 2860, 1730, 1610, 1510,
27
spectrum was not measured. ½aꢀ +170ꢁ (c 0.19, H2O).
D
1H NMR (D2O, signals for the glucopyranose moiety
could be assigned, except for the anomeric protons.) d
3.24 (1H, br ddd, J = 3.4, 4.8, 9.8 Hz, C5H of thiopyra-
nose), 3.34, 3.41 (each 1H, m, C5H · 2 of thiopyranos-
es), 3.50 (3H, s, C1OCH3), 3.56 (1H, t, J = 9.8 Hz,
C4H), 3.64 (1H, dd, J = 3.9, 9.8 Hz, C2H), 3.67–3.79
(7H), 3.87–4.00 (9H), 4.10–4.17 (2H), 4.22 (1H, dd,
J = 4.9, 9.8 Hz, C6HH), 4.79 (1H, d, J = 2.9 Hz, ano-
meric proton), 4.82 (1H, d, J = 2.9 Hz, anomeric proton),
4.83 (1H, d, J = 2.9 Hz, anomeric proton), 4.88 (1H, d,
J = 3.9 Hz, anomeric proton). 13C NMR (D2O) d 40.8,
40.9, 43.3, 55.4, 66.7, 60.3, 66.9, 67.0, 69.8, 70.2, 71.4,
73.6, 73.7, 74.23, 74.25, 74.31, 74.32, 74.34, 75.28,
75.34, 75.40, 81.68, 81.71, 81.92, 99.5. FAB-MS (nega-
tive mode,%, rel int) 787 (1.0, [M+Na37ClÀH]À), 785
(1.0, [M+Na35ClÀH]À), 765 (1.8, [M+37Cl]À), 763 (2.4,
[M+35Cl]À), 749 (1.6, [M+NaÀ2H]À), 727 (19,
[MÀH]À). FAB-HRMS (negative mode) Found
m/z = 727.1591. Calcd for C25H43O18S3: [MÀH]À,
727.1612.
1
1250, 1070, 1040, 820, 710 cmÀ1. H NMR (C6D6) d
3.11 (3H, s, C1OCH3), 3.23, 3.241, 3.244, 3.246, 3.25,
3.27, 3.27, 3.279, 3.283, 3.29 (each 3H, s, CH3O),
3.40–3.54 (4H, C5H of pyranose A, B, and C, C6HH
of A), 3.59 (1H, m, C6HH of pyranose C), 3.83–3.91
(4H, C2H of pyranose B and C, C6HH of pyranose
A, C6HH), 3.91 (1H, dd, J = 3.0, 9.2 Hz, C2H of pyra-
nose A), 4.02 (1H, t, J = 9.3 Hz, C4H of pyranose A),
4.05 (1H, dd, J = 3.4, 8.8 Hz, C6HH), 4.10 (1H, t,
J = 10.7 Hz, C4H of pyranose B), 4.08–4.10 (1H, m,
C6HH of pyranose A), 4.16–4.33 (5H, C3H of pyranose
A, B, and C, C5H, C6HH of pyranose B), 4.17, 4.25
(each 1H, d, J = 11.8 Hz, ArCH2O), 4.37 (1H, dd,
J = 3.9, 10.7 Hz, C6HH of pyranose C), 4.44, 4.54 (each
1H, d, J = 11.2 Hz, ArCH2O), 4.46, 4.55 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.47, 4.61 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.48 (1H, d, J = 3.4 Hz, C1H
of pyranose C), 4.53 (1H, dd, J = 3.4 Hz, C1H of pyra-
nose B), 4.58 (1H, d, J = 3.0 Hz, C1H of pyranose A),
4.59, 5.00 (each 1H, d, J = 10.7 Hz, ArCH2O), 4.88,
5.08 (each 1H, d, J = 10.8 Hz, ArCH2O), 4.89, 5.22
(each 1H, d, J = 10.7 Hz, ArCH2O), 4.92, 5.08 (each
1H, d, J = 10.2 Hz, ArCH2O), 4.92, 5.04 (each 1H, d,
J = 10.2 Hz, ArCH2O), 4.93, 5.20 (each 1H, d,
J = 10.8 Hz, ArCH2O), 5.29 (1H, d, J = 3.4 Hz, C1H),
5.42 (1H, dd, J = 3.4, 10.2 Hz, C2H), 6.03 (1H, t,
J = 10.2 Hz, C4H), 6.60 (1H, t, J = 10.2 Hz, C3H),
6.68–8.09 (55H, aromatic protons). 13C NMR (C6D6) d
41.6, 42.2, 42.5, 54.68, 54.71, 54.74, 54.75, 54.80, 55.3,
67.68, 67.71, 67.80, 68.1, 69.4, 70.0, 71.5, 72.0, 72.2,
72.5, 72.8, 73.0, 75.5, 75.6, 75.9, 76.0, 80.95, 80.99,
81.4, 82.36, 82.43, 82.7, 83.5, 83.56, 83.7, 85.26, 85.34,
85.42, 97.5, 113.89, 113.91, 114.03, 114.05, 114.12,
114.14, 114.16, 128.3, 128.4, 128.5, 128.6, 128.7,
129.46, 129.51, 129.56, 129.60, 129.69, 129.72, 129.80,
129.83, 129.96, 130.16, 130.20, 130.6, 131.39, 131.44,
131.69, 131.82, 131.88, 132.13, 132.21, 132.9, 133.1,
133.2, 159.47, 159.57, 159.58, 159.61, 159.67, 159.69,
159.71, 159.74, 165.4, 165.8, 166.3. ESI-MS (%, rel int)
4.36. Tetrahydropyranyl 4,6-O-(4-methoxyphenyl)meth-
ylidene-5-deoxy-5-thio-a-D-glucopyranoside (59)
A mixture of 6a (3.40 g, 12.1 mmol, a mixture of 90:10
diastereomers at the asymmetric center of the THP
group), anisaldehyde dimethyl acetal (3.0 mL,
17.6 mmol), and in DMF (20.0 mL) was stirred with
camphorsulfonic acid (10.0 mg, 43.0 lmol) at 0 ꢁC for
2 h. After neutralization by the addition of Et3N, the
mixture was poured into H2O and extracted with
EtOAc. The combined organic extracts were washed
with brine, dried over MgSO4, and then concentrated
in vacuo. Purification of the residue by silica gel column
chromatography (EtOAc/benzene 40:60) gave 59 (2.90 g,
7.26 mmol, 60%) as a colorless solid. The 1H NMR
spectra suggested that the product consists of a pair of
diastereomers due to an asymmetric center in the THP
moiety (90:10). IR (KBr) 3495, 3350, 2920, 2845, 1620,
1
1520, 1250, 1130, 1070, 1030, 970, 825 cmÀ1. H NMR

5138
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
(CDCl3, signals for the major isomer and some signals
for the minor isomer are only described. a = 0.9,
b = 0.1) d 1.57–1.86 (6H, C03H2, C04H2, C05H2), 2.85
(1H · b, d, J = 6.8 Hz, C2OH), 2.96 (1H · a, d,
J = 6.8 Hz, C2OH), 3.05 (1H · a, d, J = 1.5 Hz,
C3OH), 3.06 (1H · b, d, J = 1.5 Hz, C3OH), 3.29
(1H · a, ddd, J = 4.9, 10.3, 11.2 Hz, C5H), 3.55
(1H · a, br d, J = 11.2 Hz, C06HH), 3.71 (1H · a, t,
J = 11.2 Hz, C6HH), 3.79 (1H · a, t, J = 9.3 Hz, C4H),
3.80 (3H · a, s, CH3O), 3.91–3.98 (3H · a, C2H, C3H,
C06HH), 4.12 (1H · a, dd, J = 4.9, 11.2 Hz, C6HH),
4.25 (1H · b, dd, J = 4.9, 10.7 Hz, C6HH), 4.89
(1H · b, d, J = 2.9 Hz, C1H), 4.95 (1H · b, br t,
J = 3.4 Hz, C02H), 5.01 (1H · a, br t, J = 3.4 Hz,
C02H), 5.05 (1H · a, d, J = 2.9 Hz, C1H), 5.57 (1H, s,
ArCH(OR)2), 6.87–6.91 (2H, aromatic protons), 7.40–
7.44 (2H, aromatic protons). 13C NMR (CDCl3, signals
for the major isomer are described.) d 19.5, 25.1, 30.2,
35.1, 55.3, 63.0, 68.5, 72.4, 75.5, 77.4, 83.7, 94.9, 101.8,
113.7, 127.5, 129.8, 160.2. EI-MS (%, rel int) 398 (11,
M+), 314 (18, [MÀdihydropyran]+), 313 (20,
[MÀTHP]+), 85 (100, THP+). EI-HRMS Found
m/z = 398.1368. Calcd for C19H26O7S: M+, 398.1399.
J = 2.9 Hz, C1H), 4.87 (1H · b, br t, J = 2.9 Hz,
C20H), 4.97 (1H · a, br t, J = 2.9 Hz, C20H), 4.98
(1H · a, d, J = 2.9 Hz, C1H), 5.50 (1H · a, s, ArCH(-
OR)2), 5.51 (1H · b, s, ArCH(OR)2), 6.69–6.80 (6H,
aromatic protons), 7.16–7.33 (6H, aromatic protons).
13C NMR (CDCl3, signals for the major isomer are de-
scribed.) d 18.4, 25.3, 30.0, 35.61, 55.11, 55.11, 55.16,
61.6, 68.5, 72.4, 75.8, 75.8, 79.6, 82.8, 84.9, 93.96,
101.1, 113.4, 113.5, 113.6, 127.1, 128.2, 129.4, 129.8,
130.3, 131.1, 159.1, 159.1, 159.8. EI-MS (%, rel int)
638 (0.1, M+), 517 (2, [MÀMPM]+), 121 (100,
MPM+), 85 (45, THP+). EI-HRMS Found m/
z = 638.2532. Calcd for C35H42O9S: M+, 638.2550.
4.38. Tetrahydropyranyl 2,3,6-tri-O-(4-methoxyphe-
nyl)methyl-5-deoxy-5-thio-a-D-glucopyranoside (61) and
2,3,6-tri-O-(4-methoxyphenyl)methyl-5-deoxy-5-thio-a-
D-glucopyranose (62)
To a mixture of 60 (224 mg, 350 lmol), finely powdered
molecular sieves UOP type AW30037 (100 mg) and
BH3ÆNMe3 (102 mg, 1.40 mmol) in THF (3.0 mL), AlCl3
(186 mg 1.40 mmol) were added at À15 ꢁC. Triethyl-
amine (1.0 mL) was added to the mixture after stirring
at the same temperature for 1.5 h. The mixture was fil-
tered and the filtrate was stirred with 10% citric acid
aqueous solution (10 mL) and EtOAc (20 mL). After
6 h stirring, the organic solution was separated and it
was washed with H2O and brine successively, dried over
MgSO4, and then concentrated in vacuo. Purification of
the residue by silica gel column chromatography
(EtOAc/benzene 5:95) gave the desired 61 (91.3 mg,
144 lmol, 41%) and 62 (55.0 mg, 98.0 lmol, 28%) both
as syrups.
4.37. Tetrahydropyranyl 2,3-di-O-(4-methoxy)phenyl-
methyl-4,6-O-(4-methoxy)phenylmethylidene-5-droxy-
5-thio-a-D-glucopyranoside (60)
To a mixture of 59 (627 mg, 1.58 mmol) and NaH
(114 mg, 4.73 mmol) in DMF (10.0 mL), MPMBr (ca.
50% solution in toluene, 1.5 mL, ca. 4.73 mmol) was
added at room temperature. After the mixture was stir-
red at the same temperature for 2 h, MeOH (0.3 mL)
and Et3N (1.0 mL) were added successively. After stir-
ring for 30 min, the mixture was poured into H2O and
extracted with EtOAc. The combined organic extracts
were washed with brine, dried over MgSO4, and then
concentrated in vacuo. The residue was dissolved in pyr-
idine (3.0 mL), and the solution was stirred with Ac2O
(1.0 mL) at room temperature for 1 h to convert the
resulting anisic alcohol into the corresponding acetate.
After concentration in vacuo, purification of the residue
by silica gel column chromatography (EtOAc/hexane
20:80) gave 60 (1.01g, 1.58 mmol, 100%) as a syrup.
26
4.38.1. Physical data for 61. ½aꢀ +129ꢁ (c 1.10, CHCl3).
D
IR (film) 3470, 2935, 1610, 1510, 1250, 1095, 1030, 970,
820 cmÀ1 1H NMR (C6D6) d 1.25–1.80 (6H, C30H2,
.
C40H2, C50H2), 3.16 (1H, br s, C4OH), 3.287, 3.290,
3.293 (each 3H, s, CH3O), 3.45 (1H, br d, J = 10.7 Hz,
C60HH), 3.50 (1H, ddd, J = 3.9, 5.8, 9.3 Hz, C5H),
3.80 (1H, dd, J = 3.9, 9.8 Hz, C6HH), 3.88 (1H, dd,
J = 5.8, 9.8 Hz, C6HH), 3.93 (1H, br dd, J = 2.9,
9.3 Hz, C2H), 4.05–4.12 (3H, C3H, C4H, C60HH),
4.32 (2H, s, ArCH2O), 4.41, 4.57 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.78, 5.08 (each 1H, d,
J = 10.7 Hz, ArCH2O), 5.22 (1H, d, J = 2.9 Hz, C1H),
5.31 (1H, t, J = 2.9 Hz, C20H), 6.73–6.78 (6H, aromatic
protons), 7.18–7.23 (6H, aromatic protons). 13C NMR
(C6D6) d 19.1, 25.8, 30.5, 42.4, 54.7, 54.7, 54.7, 61.6,
69.4, 71.9, 73.1, 75.2, 75.3, 75.5, 82.6, 84.0, 94.1, 114.0,
114.0, 114.1, 129.4, 129.70, 129.74, 130.6, 130.9, 131.7,
159.66, 159.68, 159.7. EI-MS (%, rel int) 641 (trace,
[MH]+), 555 (0.3, [MÀTHP]+), 519 (3, [MÀMPM]+),
121 (100, MPM+), 85 (43, THP+). EI-HRMS Found
m/z = 519.2064. Calcd for C27H35O8S: [MÀMPM]+,
519.2053.
1
The H NMR spectrum of this sample showed that it
consists of the isomers due to the asymmetric center in
the THP moiety (90:10). IR (film) 2935, 2849, 1610,
1515, 1460, 1365, 1300, 1250, 1170, 1075, 1030, 970,
1
825, 755 cmÀ1. H NMR (CDCl3, signals for the major
isomer and some signals for the minor isomer are only
described. a = 0.9, b = 0.1) d 1.44–1.79 (6H, C30H2,
C40H2, C50H2), 3.23 (1H · a, ddd, J = 4.4, 9.3,
11.2 Hz, C5H), 3.41 (1H · a, br d, J = 10.7 Hz,
C60HH), 3.60 (1H · a, t, J = 11.2 Hz, C6HH), 3.65,
3.66, 3.67, 3.68 (each 3H · a, s, CH3O), 3.69 (1H · a,
dd, J = 2.9, 9.3 Hz, C2H), 3.80 (1H · a, t, J = 9.3 Hz,
C4H), 3.92 (1H · a, t, J = 9.3 Hz, C3H), 3.97 (1H · a,
br t, J = 10.7 Hz, C60HH), 4.09 (1H · a, dd, J = 4.4,
11.2 Hz, C6HH), 4.16 (1H · b, dd, J = 4.4, 10.7 Hz,
C6HH), 4.49 (1H · b, d, J = 11.2 Hz, ArCHHO), 4.55,
4.58 (each 1H · a, d, J = 11.2 Hz, ArCH2O), 4.61
(1H · b, d, J = 10.3 Hz, ArCHHO), 4.67, 4.69 (each
1H · a, d, J = 10.7 Hz, ArCH2O), 4.79 (1H · b, d,
26
4.38.2. Physical data for 62. ½aꢀ +32ꢁ (c 0.86, CHCl3).
D
IR (film) 3430, 2930, 2835, 1610, 1510, 1250, 1095,
1035, 820 cmÀ1 1H NMR (C6D6) d 3.03, 3.08 (each
.
1H, br, OH), 3.286, 3.292, 3.31 (each 3H, s, CH3O),
3.68 (1H, ddd, J = 4.4, 5.4, 9.3 Hz, C5H), 3.77 (1H,

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5139
dd, J = 2.9, 9.3 Hz, C2H), 3.80 (1H, dd, J = 4.4,
10.2 Hz, C6HH), 3.85 (1H, dd, J = 5.4, 10.2 Hz,
C6HH), 3.95 (1H, t, J = 9.3 Hz, C3H), 4.05 (1H, t,
J = 9.3 Hz, C4H), 4.30, 4.31 (each 1H, d, J = 10.7 Hz,
ArCH2O), 4.39, 4.40 (each 1H, d, J = 11.2 Hz,
ArCH2O), 4.75, 4.99 (each 1H, d, J = 11.2 Hz,
ArCH2O), 4.78 (1H, d, J = 2.9 Hz, C1H), 6.75–6.80
(6H, aromatic protons), 7.15–7.20 (6H, aromatic pro-
tons). 13C NMR (C6D6) d 42.1, 54.72, 54.72, 54.76,
69.4, 71.8, 71.9, 73.1, 75.2, 75.6, 82.4, 84.4, 114.07,
114.17, 114.18, 129.4, 129.7, 129,9, 130.6, 130.7, 131.6,
159.7, 159.7, 159.9. EI-MS (%, rel int) 435 (0.6,
[MÀMPM]+), 121 (100, MPM+). EI-HRMS Found
m/z = 435.1476. Calcd for C22H27O7S: [MÀMPM]+,
435.1478.
ArCH2O), 4.83 (1H, br, C1H), 5.21 (1H, br t,
J = 9.8 Hz, C4H), 6.825, 6.832, 6.832 (each 2H, d,
J = 8.8 Hz, aromatic protons), 7.16, 7.20, 7.22 (each
2H, d, J = 8.8 Hz, aromatic protons). 13C NMR (CDCl3)
d 20.9, 40.0, 55.3, 55.3, 55.3, 68.0, 71.7, 72.8, 73.9, 74.5,
75.5, 79.8, 83.7, 113.70, 113.72, 113.9, 129.2, 129.5,
129.7, 129.7, 129.8, 130.7, 159.1, 159.2, 159.4, 169.8.
EI-MS (%, rel int) 597 (0.2, [MÀH]+), 477 (4,
[MÀMPM]+), 121 (100, MPM+). EI-HRMS Found
m/z = 477.1606. Calcd for C24H29O9S: [MÀMPM]+,
477.1583.
4.39.2. Preparation from 62. A solution of 62 (89.1 mg
160 lmol) in a mixture of pyridine (2.0 mL) and Ac2O
(1.0 mL) was stirred at room temperature for 6 h. After
concentration under reduced pressure, silica gel column
chromatography of the residue (EtOAc/hexane 5:95)
4.39. 2,3,6-Tri-O-(4-methoxy)phenylmethyl-4-O-acetyl-5-
deoxy-5-thio-a-D-glucopyranoside (63)
gave the corresponding diacetate (103 mg, 160 lmol,
26
D
0.68, CHCl3). IR (KBr) 2950, 2840, 1750, 1620, 1515,
100%) as a colorless solid. mp 97–98 ꢁC. ½aꢀ +121ꢁ (c
4.39.1. Preparation from 61. A solution of 61 (260 mg,
406 lmol) in a mixture of Ac2O (1.0 mL), pyridine
(2.0 mL) was stirred at room temperature for 6 h. After
concentration in vacuo, silica gel column chromatog-
raphy of the residue (EtOAc/hexane 20:80) gave the cor-
1370, 1250, 1220, 1100, 1030, 820 cmÀ1 1H NMR
.
(CDCl3) d 1.87 2.16 (each 3H, s, CH3CO), 3.41–3.46
(2H, C5H, C6HH), 3.51 (1H, m, C6HH), 3.72 (1H, t,
J = 9.8 Hz, C3H), 3.77, 3.77, 3.78 (each 3H, s, CH3O),
3.84 (1H, dd, J = 3.4, 9.8 Hz, C2H), 4.36, 4.40 (each
1H, d, J = 11.7 Hz, ArCH2O), 4.50, 4.61 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.51, 4.77 (each 1H, d,
J = 10.7 Hz, ArCH2O), 5.23 (1H, t, J = 9.8 Hz, C4H),
6.15 (1H, d, J = 3.4 Hz, C1H), 6.82, 6.85, 6.85 (each
2H, J = 8.8 Hz, aromatic protons), 7.16, 7.20, 7.22 (each
2H, J = 8.8 Hz, aromatic protons). 13C NMR (CDCl3) d
20.7, 21.0, 41.1, 55.11, 55.12, 55.14, 68.0, 70.5, 72.3,
73.0, 75.3, 74.2, 79.7, 82.3, 113.6, 113.6, 113.7, 129.0,
129.39, 129.42, 129.45, 129.7, 130.6, 159.0, 159.2,
159.3, 169.3, 169.6. EI-MS (%, rel int) 519 (3.0,
[MÀMPM]+), 121 (100, MPM+). EI-HRMS Found
m/z = 519.1721. Calcd for C26H31O9S: [MÀMPM]+,
519.1689. A mixture of the diacetate thus obtained
(100 mg, 158 lmol) and hydrazine acetate (16.6 mg,
0.18 mmol) in DMF (1.0 mL) was stirred at room tem-
perature for 9 h. The mixture was poured into H2O
and extracted with EtOAc (·3). The combined extracts
were washed with brine, dried over MgSO4, and then
concentrated in vacuo. Silica gel column chromato-
graphy of the residue (EtOAc/benzene 8:92) gave 63
(72.6 mg, 129 lmol, 81%) as a solid. The 1H NMR
and 13C NMR spectra of this sample were identical to
those prepared from 61.
responding acetate (268 mg, 393 lmol, 97%) as a
26
D
2940, 2840, 1750, 1610, 1510, 1245, 1100, 1030, 970,
colorless syrup. ½aꢀ +98ꢁ (c 2.35, CHCl3). IR (film)
820 cmÀ1 1H NMR (C6D6) d 1.29–1.79 (6H, C30H2,
.
C40H2, C50H2), 1.71 (3H, s, CH3CO), 3.29 (9H, s,
CH3O · 3), 3.44 (1H, br t, J = 11.2 Hz, C60HH), 3.54–
3.66 (3H, C5H, C6H2), 3.88 (1H, dd, J = 2.9, 9.8 Hz,
C2H), 4.09 (1H, dt, J = 2.4, 11.2 Hz C60HH), 4.16
(1H, t, J = 9.8 Hz, C3H), 4.24, 4.28 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.38, 4.48 (each 1H, d, J = 11.2
Hz, ArCH2O), 4.68, 4.98 (each 1H, d, J = 10.7 Hz,
ArCH2O), 5.12 (1H, d, J = 2.9 Hz, C1H), 5.27 (1H,
t,J = 2.9 Hz, C20H), 5.73 (1H, t, J = 9.8 Hz, C4H),
6.76, 6.76, 6.77 (each 2H, d, J = 8.8 Hz, aromatic pro-
tons), 7.22, 7.23, 7.28 (each 2H, d, J = 8.8 Hz, aromatic
protons), 7.27–7.31 (2H, aromatic protons). 13C NMR
(C6D6) d 20.0, 20.7, 25.8, 30.5, 41.0, 54.8, 54.8, 54.8,
61.5, 69.2, 72.5, 73.2, 75.5, 75.2, 75.6, 80.7, 84.4, 94.0,
113.97, 114.0, 114.01, 129.1, 129.7, 129.8, 130.4, 130.9,
131.7, 159.5, 159.73, 159.76, 169.4. EI-MS (%, rel int)
597 (trace, [MÀTHP]+), 561 (2, [MÀMPM]+), 121
(100, MPM+). EI-HRMS Found m/z = 561.2142. Calcd
for C29H37O9S: [MÀMPM]+, 561.2158. A solution of
the acetate thus obtained (268 mg, 393 lmol) in a mix-
ture of MeOH (4.0 mL) and THF (1.0 mL) was stirred
with cat. HClO4 at room temperature for 6 h. After neu-
tralization by addition of Et3N, the mixture was concen-
trated in vacuo. Purification of residue by silica gel
column chromatography (EtOAc/benzene 8:92) gave
63 (167 mg, 279 lmol, 71%) as a solid. The yield was
4.40. 2,3,6-Tri-O-(4-methoxy)phenylmethyl-4-O-acetyl-5-
thio-a-D-glucopyranosyl trichloroacetimidate (64)
According to general procedure A, a solution of DBU in
CH2Cl2, (26 lM, 0.1 mL) was added at À15 ꢁC to a mix-
ture of 63 (32.5 mg, 54.2 lmol) and CCl3CN (46.8 lL,
325 lmol) in CH2Cl2 (1.0 mL). After stirring for
30 min at the same temperature, the mixture was con-
centrated in vacuo. Purification of the residue by silica
gel column chromatography (EtOAc/benzene 5:95) gave
64 (40.0 mg, 53.8 lmol, 100 %) as a syrup. IR (film)
3750, 2950, 1750, 1670, 1610, 1510, 1250, 1100, 1030,
82% according to recovery of the starting acetate. mp
27
D
2955, 2870, 1750, 1610, 1515, 1250, 1170, 1100, 1030,
109–110 ꢁC. ½aꢀ +38ꢁ (c 0.63, CHCl3). IR (KBr) 3360,
1
820 cmÀ1. H NMR (CDCl3) d 1.84 (3H, s, CH3CO),
2.58 (1H, br, C1OH), 3.43–3.52 (3H, C3H, C6H2),
3.74–3.81 (2H, C2H, C5H), 3.77, 3.776, 3.78 (each 3H,
s, CH3O), 4.33, 4.40 (each 1H, d, J = 11.7 Hz,
ArCH2O), 4.53, 4.75 (each 1H, d, J = 10.8 Hz,
ArCH2O), 4.58, 4.65 (each 1H, d, J = 11.2 Hz,
.
820 cmÀ1 1H NMR (C6D6) d 1.69 (3H, s, CH3CO),
3.282, 3.286, 3.289 (each 3H, s, CH3O), 3.53 (1H, dd,

5140
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
J = 5.4, 10.3 Hz, C6HH), 3.56 (1H, dd, J = 4.4, 10.3 Hz,
C6HH), 3.75 (1H, ddd, J = 4.4, 5.4, 10.7 Hz, C5H), 3.86
(1H, dd, J = 2.9, 9.3 Hz, C2H), 4.12 (1H, t, J = 9.3 Hz,
C3H), 4.18, 4.25 (each 1H, d, J = 11.7 Hz, ArCH2O),
4.30, 4.42 (each 1H, d, J = 11.2 Hz, ArCH2O), 4.65,
4.92 (each 1H, d, J = 11.2 Hz, ArCH2O), 5.74 (1H, dd,
J = 9.3, 10.7 Hz, C4H), 6.75, 6.75, 6.76 (each 2H, d,
J = 8.8 Hz, aromatic protons), 7.16, 7.18, 7.24 (each
2H, d, J = 8.8 Hz, aromatic protons), 8.58 (1H, s,
C( = NH)CCl3). This sample was gradually decom-
posed, thus it was immediately used for the next step.
2H, d, J = 8.8 Hz, aromatic protons). 13C NMR (CDCl3)
d 55.25, 55.26, 55.29, 55.31, 62.3, 69.0, 73.4, 75.0, 78.3,
78.7, 82.1, 99.3, 101.2, 113.5, 113.7, 113.8, 127.3,
129.6, 129.7, 130.0, 130.3, 130.9, 159.3, 159.4, 160.0.
EI-MS (%, rel int) 552 (0.5, M+), 431 (57, [MÀMPM]+),
121 (100, MPM+). EI-HRMS Found m/z = 431.1715.
Calcd for C23H27O8: [MÀMPM]+, 431.1706. To a mix-
ture of the MPM ether thus obtained (247 mg,
459 lmol), finely powdered molecular sieves UOP type
AW300 (100 mg) and BH3 Æ NMe3 (102 mg, 1.39 lmol)
in THF (3.0 mL), AlCl3 (188 mg, 1.41 lmol) were added
at À15 ꢁC. Triethylamine (1.0 mL) was added to the
mixture after stirring at the same temperature for
30 min,. The mixture was filtered and the filtrate was
stirred with 10% citric acid aqueous solution (10 mL)
and EtOAc (20 mL). After 1 h, the organic solution
was separated, and it washed with H2O and brine suc-
cessively, dried over MgSO4, and then concentrated in
vacuo. Purification of the residue by silica gel column
4.41. Methyl 2,3,6-tri-O-(4-methoxyphenyl)methyl-a-D-
glucopyranoside (65)
A mixture of methyl a-D-glucopyranoside (1.3 g,
6.7 mmol), anisaldehyde dimethyl acetal (1.2 mL,
7.4 mmol), and in DMF (10.0 mL) was stirred with cam-
phorsulfonic acid (10 mg, 43.0 lmol) at 70 ꢁC for 4 h.
After neutralization by the addition of Et3N, the mix-
ture was poured into H2O and extracted with EtOAc.
The combined organic extracts were washed with brine,
dried over MgSO4, and then concentrated in vacuo.
Purification of the residue by silica gel column chromat-
ography (benzene/EtOAc 60:40) gave methyl 4,6-O-(4-
methoxybenzylidene) glucopyranoside (1.3 g, 4.1 mmol,
62%) as a solid. 1H NMR (CDCl3) d 2.21 (1H, d,
J = 9.8 Hz, C2OH), 2.64 (1H, d, J = 2.0 Hz, C3OH),
3.44 (3H, s, CH3O), 3.46 (1H, t, J = 9.3 Hz, C4H),
3.61 (1H, dt, J = 3.9, 9.3 Hz, C2H), 3.71 (1H, t,
J = 9.8 Hz, C6HH), 3.77 (1H, C5H), 3.78 (1H, s,
CH3O), 3.90 (1H, dt, J = 2.0, 9.3 Hz, C3H), 4.26 (1H,
dd, J = 4.3, 9.8 Hz, C6HH), 4.78 (1H, d, J = 3.9 Hz,
C1H), 5.47 (1H, s, ArCH(OR)2), 6.86, 6.88 (each 1H,
aromatic proton), 7.38, 7.41 (each 1H, aromatic proton).
To a mixture of the diol thus obtained (526 mg,
1.69 mmol) and NaH (121 mg, 5.06 mmol) in DMF
(8.0 mL), MPMBr (ca. 50% solution in toluene,
1.6 mL, ca. 5.06 mmol) was added at room temperature.
After the mixture was stirred at the same temperature
for 2 h, MeOH (0.5 mL) and Et3N (1.0 mL) were added
successively. After stirring for 30 min, the mixture was
poured into H2O and extracted with EtOAc. The com-
bined organic extracts were washed with brine, dried
over MgSO4, and then concentrated in vacuo. Purifica-
tion of the residue by silica gel column chromatography
(EtOAc/benzene 95:5) gave methyl 2,3-bis-O-(4-meth-
oxy)phenylmethyl-4,6-O-(4-methoxybenzylidene)-a-D-
glucopyranoside (881 mg, 1.64 mmol, 97%) as a solid.
Analytical sample was obtained by recrystallization
chromatography (EtOAc/benzene 10:90) gave 65
27
D
CHCl3). IR (film) 3480, 2910, 1610, 1510, 1250, 1050,
(186 mg, 335 lmol, 73%) as a syrup. ½aꢀ +2.0ꢁ (c 0.16
1030, 840 cmÀ1 1H NMR (CDCl3) d 2.41 (1H, br,
.
OH), 3.35 (3H, s, CH3O), 3.47 (1H, dd, J = 3.9,
9.8 Hz, C2H), 3.53 (1H, t, J = 9.3 Hz, C4H), 3.58–3.68
(3H, C5H, C6H2), 3.72 (1H, t, J = 9.3 Hz, C3H), 3.76,
3.77, 3.77 (each 3H, s, CH3O), 4.45, 4.49 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.55 (1H, d, J = 3.9 Hz, C1H),
4.58, 4.69 (each 1H, d, J = 11.2 Hz, ArCH2O), 4.64,
4.89 (each 1H, d, J = 11.2 Hz, ArCH2O), 6.83, 6.84,
6.86 (each 2H, d, J = 8.8 Hz, aromatic protons), 7.21,
7.27, 7.27 (each 2H, d, J = 8.8 Hz, aromatic protons).
13C NMR (CDCl3) d 55.1, 55.15, 55.18, 55.18, 69.2,
69.8, 70.7, 72.8, 73.2, 75.0, 79.2, 81.1, 98.2, 113.7,
113.8, 114.0, 129.2, 129.6, 129.7, 130.1, 130.2, 131.0,
159.2, 159.3, 159.4. EI-MS (%, rel int) 553 (trace,
[MÀH]+), 433 (10, [MÀMPM]+), 313 (7.5,
[MÀMPM · 2+H]+), 121 (100, MPM+). EI-HRMS
Found
m/z = 433.1848.
Calcd
for
C23H29O8:
[MÀMPM]+, 433.1862.
4.42. Methyl 4-O-[20,30,60-tri-O-(4-methoxyphenyl)meth-
yl-40-O-acetyl-50-thio-a-D-glucopyranosyl]-2,3,6-tri-O-(4-
methoxyphenyl)methyl-a-D-glucopyranoside (66)
According to general procedure B, a suspension of a mix-
ture of 64 (200 mg, 371 lmol), 65 (275 mg, 370 lmol),
and powdered MS4A (200 mg) in CH2Cl2 (4.0 mL)
was stirred at room temperature for 30 min. After cool-
ing to À78 ꢁC, TESOTf (90 lmol/mL solution in
CH2Cl2, 200 lL, 0.05 equiv) was added to the suspen-
sion. The mixture was stirred at the same temperature
for 2 h and Et3N (10 lL) was added. The resulting mix-
ture was filtered through a silica gel pad, which was
washed with EtOAc. After concentration in vacuo, the
residue was subjected to a silica gel column chromato-
graphy (EtOAc/hexane 30:70) to give 66 (330 mg,
293 lmol, 79%) as a syrup. The 1H NMR spectra of this
sample suggested that the product consists of a pair of
diastereomers at the newly introduced glycoside linkage
(a:b = 90:10). Analytical sample for the major isomer
was obtained by HPLC (lBondasphere 150 SIL-100,
7.8 (B) · 30 mm, EtOAc/hexane 20:80, 4.0 mL/min).
from hexane/EtOAc (20:80) to give colorless needles.
26
D
2950, 2910, 1615, 1515, 1465, 1370, 1250, 1170, 1080,
mp 127–128 ꢁC. ½aꢀ À48ꢁ (c 0.94, CHCl3), IR (KBr)
1030, 825 cmÀ1 1H NMR (CDCl3) d 3.37 (3H, s,
.
C1OCH3), 3.48 (1H, dd, J = 3.4, 9.3 Hz, C2H), 3.53
(1H, t, J = 9.3 Hz, C4H), 3.65 (1H, t, J = 10.3 Hz
C6HH), 3.77 (1H, C5H), 3.77, 3.78, 3.80 (each 3H, s,
CH3O), 3.97 (1H, t, J = 9.3 Hz, C3H), 4.21 (1H, dd,
J = 4.9, 10.3 Hz, C6HH), 4.45 (1H, d, J = 3.4 Hz,
C1H), 4.60, 4.76 (each 1H, d, J = 11.7 Hz, ArCH2O),
4.73, 4.79 (each 1H, d, J = 10.7 Hz, ArCH2O), 5.47
(1H, s, ArCH(OR)2), 6.82, 6.84, 6.88 (each 2H, d,
J = 8.8 Hz, aromatic protons), 7.26, 7.27, 7.38 (each

Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
5141
However, these conditions did not provide pure minor
isomer. tR = 92 min (above conditions). ½aꢀ +68ꢁ (c
(each 1H, d, J = 11.7 Hz, ArCH2O), 4.53, 4.61 (each
1H, d, J = 11.7 Hz, ArCH2O), 4.68 (1H, d, J = 3.4 Hz,
C1H), 4.70 (1H, dd, J = 9.3, 9.8 Hz, C4H), 4.77, 5.04
(each 1H, d, J = 11.0 Hz, ArCH2O), 4.81, 5.21 (each
1H, d, J = 11.7 Hz, ArCH2O), 6.02 (1H, d, J = 2.9 Hz,
C10H), 6.70–6.81 (12H, aromatic protons), 7.13–7.36
(12H, aromatic protons). 13C NMR (C6D6) d 42.7,
54.69, 54.69, 54.69, 54.72, 54.72, 54.9, 69.6, 70.0, 70.4,
72.1, 72.42, 72.45, 73.2, 73.3, 73.5, 75.2, 75.5, 80.3,
81.2, 82.3, 82.7, 83.7, 97.9, 114.02, 114.05, 114.07,
114.07, 114.09, 114.14, 128.2, 128.5, 129.36, 129.39,
129.6, 129.8, 130.7, 130.96, 130.99, 131.1, 131.7, 131.8,
159.3, 159.58, 159.61, 159.67, 159.71, 159.74. FD-MS
(%, rel int): 1092 (22, M+), 971 (100, [MÀMPM]+).
FD-HRMS Found m/z = 1092.4557. Calcd for
C61H72O16S: M+, 1092.4541.
26
D
0.98, CHCl3). IR (film) 2920, 2855, 1735, 1610, 1510,
1
1245, 1095, 1030, 820 cmÀ1. H NMR (CDCl3) d 1.82
(3H, s, CH3CO) 3.10 (1H, dt, J = 4.4, 10.7 Hz, C50H),
3.20, 3.25 (each 1H, dd, J = 4.4, 9.8 Hz, C60HH), 3.37
(3H, s, CH3O), 3.55 (1H, dd, J = 3.4, 9.3 Hz, C2H),
3.68, 3.73, 3.758, 3.764, 3.764, 3.77 (each 3H, s,
CH3O), 3.66 (1H, dd, J = 2.9, 10.3 Hz, C6HH), 3.71–
3.78 (3H, C6HH, C20H, C30H), 3.90 (1H, br d,
J = 9.8 Hz, C5H), 4.04 (1H, t, J = 9.3 Hz, C3H), 4.18
(1H, dd, J = 9.3, 9.8 Hz, C4H), 4.18, 4.29 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.42, 4.71 (each 1H, d,
J = 10.7 Hz, ArCH2O), 4.45, 4.53 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.46, 4.49 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.47 (2H, s, ArCH2O), 4.52
(1H, d, J = 3.4 Hz, C1H), 4.55, 4.92 (each 1H, d,
J = 11.2 Hz, ArCH2O), 5.20 (1H, t, J = 10.7 Hz,
C40H), 5.49 (1H, d, J = 2.9 Hz C10H), 5.71 (2H, d,
J = 8.8 Hz, aromatic protons), 6.79–6.83 (10H, aromatic
protons), 7.00 (2H, d, J = 8.8 Hz, aromatic protons),
7.10–7.16 (6H, aromatic protons), 7.20–7.22 (4H, aro-
matic protons). 13C NMR (CDCl3) d 20.9, 40.1, 55.12,
55.15, 55.18, 55.21, 55.23, 55.23, 55.23, 67.9, 69.22,
69.25, 71.7, 72.9, 72.9, 72.97, 72.99, 73.6, 74.7, 75.3,
79.8, 79.9, 80.2, 81.7, 83.1, 97.7, 113.6, 113.72, 113.75,
113.8, 128.3, 128.8, 129.0, 129.35, 129.38, 129.78,
129.81, 129.99, 130.0, 130.3, 130.7, 130.8, 158.9,
158.96, 159.0, 159.09, 159.12, 159.4, 169.7. FD-MS (%,
rel int) 1135 (12, MH+) 1134 (7, M+), 1133 (19,
[MÀH]+), 1014 (63, [MÀMPM+H]+), 1013 (100,
[MÀMPM]+), 893 (15, [MÀ2 · MPM+H]+). FD-
4.43.2. Reaction using a mixture of isomers in preparative
scale. A solution of the anomeric mixture of 66 (189 mg,
166 lmol, an anomeric mixture, a:b = 90:10), and
NaOMe (31.2 mg, 0.6 mmol) in a mixture MeOH
(5.0 mL) and THF (1.0 mL) was stirred at 40 ꢁC for
4 h. After neutralization by the addition of 2 M HCl
aqueous solution, the mixture was poured into H2O
and extracted with EtOAc (·3). The combined extracts
were washed with brine, dried over MgSO4, and then
concentrated in vacuo. Purification of the residue by sil-
ica gel column chromatography (EtOAc/benzene 10:90)
gave an anomeric mixture of 67 (a:b = 90:10, 178 mg,
167 lmol, 98%) as a syrup. The major signals in the
1H NMR spectrum of this sample were identical to those
prepared from pure 66.
HRMS
Found
m/z = 1134.4657.
Calcd
for
C63H74O17S: M+, 1134.4647.
4.44. Methyl 2,3,6-tri-O-(4-methoxyphenyl)methyl-4-O-
[20,30,60-tri-O-(4-methoxyphenyl)methyl-40-O-[200,300,600-
tri-O-(4-methoxyphenyl)methyl-400-O-acetyl-500-thio-a-D-
glucopyranosyl]-50-thio-a-D-glucopyranosyl]-a-D-gluco-
pyranoside (68)
4.43. Methyl 4-O-[20,30,60-tri-O-(4-methoxyphenyl)meth-
yl-50-thio-a-D-glucopyranosyl]-2,3,6-tri-O-(4-methoxy-
phenyl)methyl-a-D-glucopyranoside (67)
4.43.1. Reaction using pure 66. A solution of 66 (21.5 mg,
18.9 lmol) and NaOMe (30.0 mg, 0.58 mmol) in a mix-
ture of MeOH (2.5 mL) and THF (0.5 mL) was stirred
at 40 ꢁC for 4 h. After neutralization by the addition
of 2 M HCl aqueous solution, the mixture was poured
into H2O and extracted with EtOAc (·3). The combined
extracts were washed with brine, dried over MgSO4, and
then concentrated in vacuo. Purification of the residue
by silica gel column chromatography (EtOAc/benzene
4.44.1. Preparation using pure 67. According to general
procedure B, a suspension of 67 (17.0 mg, 15.6 lmol),
64 (21.0 mg, 26.3 lmol), and MS4A (50 mg) in CH2Cl2
(1.0 mL) was stirred at room temperature for 30 min.
After cooling to À78 ꢁC, TESOTf (130 lmol/mL solu-
tion in CH2Cl2, 10 lL, 0.05 equiv) was added to the sus-
pension. The mixture was stirred at the same
temperature for 2 h and Et3N was added. The resulting
mixture was filtered through silica gel pad, which was
washed with EtOAc. After concentration in vacuo, the
residue was subjected to a silica gel column chromatog-
raphy (EtOAc/hexane 40:60) to give an anomeric mix-
ture of 68 (13.4 mg, 8.3 lmol, 53%) as a syrup. The
yield was 80% according to recovery of 67. The minor
isomer was removed by HPLC (lBondasphere 150
SIL-100, 7.8 (/) · 300 mm, EtOAc/hexane 35:65,
10:90) gave an anomeric mixture of 67 (18.9 mg,
26
D
IR (film) 3430, 2920, 2835, 1610, 1510, 1250, 1095,
16.8 lmol, 89%) as a syrup. ½aꢀ +37ꢁ (c 0.68, CHCl3).
1030, 820 cmÀ1 1H NMR (C6D6) d 3.05 (1H, br,
.
C04OH), 3.16 (3H, s, C1OCH3), 3.260, 3.267, 3.267,
3.272, 3.275, 3.31 (each 3H, s, CH3O), 3.55 (1H, br dt,
J = 4.9, 9.8 Hz, C05H), 3.64 (1H, dd, J = 3.4, 9.8 Hz,
C2H), 3.75 (1H, dd, J = 4.4, 9.8 Hz, C60HH), 3.87
(1H, dd, J = 5.4, 9.8 Hz, C60HH), 3.90 (1H, br d,
J = 10.3 Hz, C6HH), 3.93 (1H, dd, J = 2.9, 9.3 Hz,
C02H), 3.99 (1H, dd, J = 4.4, 10.3 Hz, C6HH), 4.04–
4.10 (2H, C03H, C04H), 4.15 (1H, ddd, J = 2.0, 4.4,
9.8 Hz, C5H), 4.30, 4.31 (each 1H, d, J = 11.7 Hz,
ArCH2O), 4.34, 4.37 (each 1H, d, J = 11.2 Hz,
ArCH2O), 4.49 (1H, t, J = 9.3 Hz, C3H), 4.49, 4.58
1
2.25 mL/min, tR = 30 min). The H NMR spectrum dis-
played small signals for the minor C100b-anomer at d
1.68 (CH3CO), 3.15 (C1OCH3), 5.73 (C004H) and 6.00,
6.01 (each anomeric proton) ppm. Comparison of peak
intensities revealed the selectivity in this reaction
(a:b = 84:16). IR (film) 2925, 2830, 1740, 1610, 1510,
1
1250, 1100, 1035, 820 cmÀ1. H NMR (C6D6, Only sig-
nals for the major anomer are described.) d 1.74 (3H, s,

5142
Y. Morii et al. / Bioorg. Med. Chem. 13 (2005) 5113–5144
CH3CO), 3.10 (3H, s, C1OCH3), 3.24, 3.26, 3.26, 3.27,
3.27, 3.277, 3.282, 3.288, 3.31 (each 3H, s, CH3O),
3.54–3.58 (2H, C006H2), 3.64 (1H, dd, J = 3.4, 9.3 Hz,
C2H), 3.75 (1H, ddd, J = 4.4, 5.9, 11.2 Hz, C005H),
3.80–3.85 (2H, C5H, C05H), 3.87 (1H, dd, J = 2.9,
9.8 Hz, C002H), 4.01–4.07 (3H, C6H2, C02H), 4.19, 4.28
(each 1H, d, J = 11.7 Hz, ArCH2O), 4.23–4.25 (3H,
C06H2, C003H), 4.33, 4.37 (each 1H, d, J = 11.7 Hz,
ArCH2O), 4.36, 4.48 (each 1H, d, J = 11.2 Hz,
ArCH2O), 4.42, 4.56 (each 1H, d, J = 11.7 Hz,
ArCH2O), 4.44 (1H, C3H), 4,45 (1H, C30H), 4.62–4.67
(2H, ArCH2O), 4.637, 4.69 (each 1H, d, J = 11.7 Hz,
ArCH2O), 4.642, 4.92 (each 1H, d, J = 11.2 Hz,
ArCH2O), 4.65 (1H, d, J = 3.4 Hz, C1H), 4.78 (1H,
C4H), 4.78, 5.19 (each 1H, d, J = 11.7 Hz, ArCH2O),
4.89, 5.20 (each 1H, d, J = 11.2 Hz, ArCH2O), 4.96
(1H, t, J = 9.8 Hz, C04H), 5.77 (1H, t, J = 9.8 Hz,
C004H), 5.79 (1H, d, J = 2.9 Hz, C01H), 6.05 (1H, d,
J = 2.9 Hz, C001H), 6.64–7.43 (36H, aromatic protons).
FD-MS (%, rel int) 1673 (44, [M+H]+), 1672 (31, M+),
1552 (94, [M+HÀMPM]+), 1551 (100, [MÀMPM]+).
FD-HRMS Found m/z = 1673.6711. Calcd for
C93H109O24S2: [M+H]+, 1673.6750.
ography to give a-anomer (59.9 mg) and b-anomer
(5.0 mg).
26
4.45.1. Physical data for a-anomer. ½aꢀ +99ꢁ (c 0.89,
D
CHCl3). IR (film) 3500, 2910, 2830, 1610, 1510,
1
1250, 1095, 1030, 820 cmÀ1. H NMR (C6D6, The se-
quence of 5-thioglucose was not assigned.) d 3.11 (3H,
s, CH3O), 3.14 (1H, br, OH), 3.24, 3.268, 3.272, 3.274,
3.278, 3.281, 3.285, 3.30, 3.31 (each 3H, s, CH3O),
3.58–3.69 (3H, C2H, Ca5H, Ca6HH), 3.79-3.87 (4H,
C6HH, Ca6HH, Cb5H, Cb6HH), 3.93 (1H, dd,
J = 2.9 and 9.3 Hz, Ca2H), 4.02–4.13 (5H, C5H,
C6HH, Ca3H, Ca4H, Cb6HH), 4.22 (1H, dd,
J = 4.4, 9.3 Hz, Cb6HH), 4.26, 4.29 (each 1H, d,
J = 11.7 Hz, ArCH2O), 4.35, 4.49 (each 1H, d,
J = 10.5 Hz, ArCH2O), 4.36, 4.36 (each 1H, ArCH2O),
4.38, 4.55 (each 1H, d, J = 11.7 Hz, ArCH2O), 4.45
(1H, t, J = 9.3 Hz, C3H), 4.48 (1H, t, J = 9.8 Hz,
Cb3H), 4.50, 4.59 (each 1H, d, J = 11.2 Hz, ArCH2O),
4.64, 4.69 (each 1H, d, J = 11.7 Hz, ArCH2O), 4.65
(1H, d, J = 3.6 Hz, C1H), 4.77, 5.01 (each 1H, d,
J = 11.2 Hz, ArCH2O), 4.790 (1H, t, J = 9.3 Hz,
C4H), 4.793, 5.20 (each 1H, d, J = 11.2 Hz, ArCH2O),
4.78, 5.23 (each 1H, d, J = 11.2 Hz, ArCH2O), 5.03
(1H, t, J = 9.8 Hz, Cb4H), 5.99 (1H, d, J = 2.9 Hz,
Cb1H), 6.12 (1H, d, J = 2.9 Hz, Ca1H), 6.63–7.44
(36H, aromatic protons). FD-MS (%, rel int) 1631
4.44.2. Reaction using a mixture of isomers. According to
general procedure B, a suspension of 67 (136 mg,
125 lmol), 63 (115 mg, 155 lmol), and MS4A (100 mg)
in CH2Cl2 (2.0 mL) was stirred at room temperature
for 30 min. After cooling to À78 ꢁC, TESOTf
(380 lmol/mL solution in CH2Cl2, 20 lL, 0.05 equiv)
was added to the suspension. The mixture was stirred
at the same temperature for 2 h, and Et3N was added.
The resulting mixture was filtered through silica gel
pad and the pad was washed with EtOAc. After concen-
tration in vacuo, the residue was subjected to a silica gel
column chromatography (EtOAc/hexane 40:60) to give
an anomeric mixture of 68 (159 mg, 95.0 lmol, 76%)
as a syrup. The products were subjected to a HPLC
(lBondasphere 150 SIL-100, 7.8 (/) · 30 mm, EtOAc/
hexane 35:65, 2.25 mL/min, tR = 30 min) to remove
two minor isomers. However, the sample still contained
the last minor isomer. The major signals in the 1H NMR
spectrum of this sample were identical to those prepared
from pure 67.
(10,
[M+H]+),
1630
(5,
M+),
1510
(71,
[M+HÀMPM]+), 1509 (100, [MÀMPM]+), FD-HRMS
Found m/z = 1631.6696. Calcd for C91H107O23S2:
[M+H]+, 1631.6566.
4.45.2. Physical data for (a100 ! 40, b10 ! 4)-isomer.
26
½aꢀ +41ꢁ (c 0.85, CHCl3). IR (film) 3495, 2930, 2835,
D
1610, 1510, 1250, 1095, 1030, 820 cmÀ1
.
1H NMR
(C6D6) d 2.87 (1H, ddd, J = 3.9, 4.9, 9.8 Hz, C50H),
3.08 (1h, br, C400OH), 3.19 (3H, s, CH3O), 3.261,
3.267, 3.275, 3.28, 3.28, 3.29, 3.294, 3.31, 3.35 (each
3H, s, CH3O), 3.57 (1H, dd, J = 3.9, 9.3 Hz, C2H),
3.54–3.58 (2H, C006H2), 3.77 (1H, t, J = 8.8 Hz,
C30H), 3.80 (1H, dd, J = 4.9, 9.3 Hz, C60HH), 3.78–
3.81 (2H, C500H, C6HH), 3.90 (1H, dd, J = 2.9,
9.3 Hz, C200H), 3.94 (1H, br d, J = 9.8 Hz, C5H),
4.077 (1H, t, J = 9.3 Hz, C300H), 4.084 (1H, t,
J = 8.8 Hz, C20H), 4.12 (1H, dd, J = 4.9, 9.3 Hz,
C60HH), 4.15 (1H, t, J = 9.3 Hz, C400H), 4.15 (1H, t,
J = 9.8 Hz, C3H), 4.18 (1H, dd, J = 3.4,10.7 Hz,
C6HH), 4.23. 4.26 (each 1H, J = 11.7 Hz, ArCH2O),
4.34 (1H, t, J = 9.3 Hz, C4H), 4.36, 4.56 (each 1H,
J = 11.7 Hz, ArCH2O), 4.40, 4.48 (each 1H,
J = 11.7 Hz, ArCH2O), 4.44, 4.61 (each 1H,
J = 11.7 Hz, ArCH2O), 4.52-4.58 (2H, ArCH2O), 4.63
(1H, d, J = 3.9 Hz, C1H), 4.66, 4.83 (each 1H,
J = 10.7 Hz, ArCH2O), 4.79, 5.03 (each 1H,
J = 11.2 Hz, ArCH2O), 4.94, 5.27 (each 1H,
J = 10.3 Hz, ArCH2O), 4.95, 5.16 (each 1H,
J = 11.7 Hz, ArCH2O), 4.96 (1H, t, J = 8.8 Hz,
C40H), 5.01 (1H, d, J = 8.8 Hz, C10H), 5.95 (1H, d,
J = 2.9 Hz, C100H),6.73-7.67 (32H, aromatic protons),
FD-MS (%, rel int) 1671 (7.3, [M+2H+K]+), 1655
(11, [M+2H+Na]+), 1632 (13, [M+2H]+), 1511 (100,
4.45. Methyl 4-O-[20,30,60-tri-O-(4-methoxyphenyl)meth-
yl-40-O-[200,300,600-tri-O-(4-methoxyphenyl)methyl-500-thio-
a-D-glucopyranosyl]-50-thio-D-glucopyranosyl]-2,3,6-tri-
O-(4-methoxyphenyl)methyl-a-D-glucopyranoside (69)
A solution of the anomeric mixture of 68 (105 mg,
62.7 lmol,
a
mixture of isomers) and NaOMe
(32.0 mg, 593 lmol) in a mixture of MeOH (2.0 mL)
and THF (0.5 mL) was stirred at 40 ꢁC for 4 h. After
neutralization by the addition of 2 M aqueous HCl
solution, the mixture was poured into H2O and extract-
ed with EtOAc (·3). The combined extracts were
washed with brine, dried over MgSO4, and then con-
centrated in vacuo. Purification of the residue by silica
gel column chromatography (EtOAc/benzene 10:90)
gave an anomeric mixture of 69 (76.8 mg, 47.1 lmol,
75%, a:b = 91:9) as a syrup. The anomeric mixture
was subjected to a medium pressure column chromat-
[M+2HÀMPM]+),
FD-HRMS
Found
m/z =
1630.6582. Calcd for C91H106O23S2: M+, 1630.6560.