Effective and chemoselective glycosylations using 2,3-unsaturated sugars

Article abstract of DOI:10.1039/c004204h

Glycosyl donors containing a double bond between C2 and C3 were designed by mimicking the reaction mechanism of lysozyme-initiated hydrolysis of mucopolysaccharides. It was found that, under various glycosylation conditions, the reactivities of 2,3-unsatu

Full text of DOI:10.1039/c004204h

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Effective and chemoselective glycosylations using 2,3-unsaturated sugars†
Shunichi Kusumi, Kaname Sasaki, Sainan Wang, Tatsuya Watanabe, Daisuke Takahashi and Kazunobu
Toshima*
Received 16th March 2010, Accepted 12th May 2010
First published as an Advance Article on the web 26th May 2010
DOI: 10.1039/c004204h
Glycosyl donors containing a double bond between C2 and C3 were designed by mimicking the
reaction mechanism of lysozyme-initiated hydrolysis of mucopolysaccharides. It was found that, under
various glycosylation conditions, the reactivities of 2,3-unsaturated glycosyl acetates were significantly
higher, while those of the corresponding 2,3-unsaturated-4-keto glycosyl acetates were much lower than
those of the corresponding 2,3-dideoxy (2,3-saturated) glycosyl acetates. Based on these results,
chemoselective glycosylations were effectively realized via combinatorial techniques in short-steps using
three types of glycosyl donors to construct several types of deoxyoligosaccharides. Furthermore, the
highly reactive 2,3-unsaturated glycosyl acetates were found to be useful in the synthesis of the
O-glycosides of low reactive tertiary alcohols.
can regioselectively hydrolyze hexasaccharides between the D and
Introduction
E-sugars,9 due to two factors, both which increase the hydrolytic
Oligosaccharides play very important roles in many biological
cleavage rate of oligosaccharides: 1) conformational distortion by
events, and accordingly, the development of novel and effective
the lysozyme forces the D-sugar to adopt an unusual half-chair
conformation (4H5), which is very similar to the conformation
synthetic methods has attracted much attention in the field of
synthetic carbohydrate chemistry.1 One of the most attractive
strategy for this purpose is chemoselective glycosylation.2 The
“armed-disarmed” concept introduced by Fraser-Reid and co-
workers has been one of the most influential ideas in this field.3
Thus, the reactivity of glycosyl donors that possess the same
leaving group at the anomeric position can be controlled by
the combinational use of electron-withdrawing and -donating
protecting groups at the C2-position. Unfortunately, this approach
cannot be directly applied to 2-deoxy glycosyl donors, which
lack a C2-substituent, and therefore, an alternative strategy is
required for the chemoselective glycosylation of 2-deoxy sugars.4
Interestingly, although 2,3-dideoxyglycosides frequently appear in
biologically important natural products, such as vineomycin B2,5
lactonamycin,6 or PI-080,7 only a few attempts at constructing the
structure, including that of Sulikowski and coworkers,8 have been
reported to date. The total synthesis of these natural products
has yet to be reported due to the difficulty in the construction
of the highly deoxygenated oligosaccharides. The purpose of
this study is to develop a novel glycosylation method inspired
by an enzymatic reaction as a new strategy in armed/disarmed
methodology, and as a powerful protocol for constructing glyco-
sidic linkages between highly deoxygenated sugars (represented by
2,3-dideoxyglycosides) and alcohols with low nucleophilicity.
Our strategy involves mimicking the features of lysozyme, which
is known to recognize the six hexose residues of mucopolysaccha-
rides (A to F sugars). Furthermore, as shown in Fig. 1(a), lysozyme
of the oxocarbenium intermediate,10 and 2) stabilization of the
resulting oxocarbenium cation via electrostatic interactions with
the carboxylate anion of Asp 52 of lysozyme.11 These factors
prompted us to design a novel class of glycosyl donors that
possess an endo double bond between the C2- and C3-positions, as
shown in Fig. 1(b). First, the introduction of an unsaturated bond
would cause distortion of the glycosyl donor into the half-chair
conformation (in its ground state) that is similar to the distorted
conformation of the mucopolysaccharide D-sugar induced by
lysozyme. Secondly, such glycosyl donors would allow for the
similar stabilization of the oxocarbenium intermediate during the
glycosylation reactions due to the location of the cationic charge at
the allylic position of the double bond. Therefore, we anticipated
that such 2,3-unsaturated glycosyl donors would exhibit high reac-
tivities under relatively mild chemical glycosylation conditions. In
contrast, 2,3-unsaturated-4-keto glycosyl donors12 possessing an
a,b-unsaturated keto structure should be significantly less reactive
than the corresponding 2,3-unsaturated glycosyl donors because
the corresponding oxocarbenium intermediate, generated by the
activation of the 2,3-unsaturated-4-keto glycosyl donor, would be
highly unstable due to the resonance effect of the a,b-unsaturated
keto system adjacent to the C1 cation, as shown in Fig. 1(c). In
this paper, we report effective and chemoselective glycosylations
using 2,3-unsaturated and 2,3-unsaturated-4-keto sugars as novel
armed and disarmed glycosyl donors, respectively.13
Results and discussion
Department of Applied Chemistry, Faculty of Science and Technology,
Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan.
E-mail: toshima@applc.keio.ac.jp; Fax: +81-45-566-1576; Tel: +81-45-
566-1576
Synthesis of 2,3-unsaturated, 2,3-dideoxy, and
2,3-unsaturated-4-keto glycosyl donors
† Electronic Supplementary Information (ESI) available: Effective and
chemoselective glycosylations using 2,3-unsaturated sugars. See DOI:
10.1039/c004204h/
As shown in Scheme 1, benzoyl (Bz)-protected 2,3-unsaturated
glycosyl acetate 1, 2,3-dideoxy glycosyl acetate 2, and
3164 | Org. Biomol. Chem., 2010, 8, 3164–3178
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Fig. 1 (a) Reaction mechanism of regioselective hydrolysis of mucopolysaccharide by lysozyme, and the concept of (b) glycosylation using 2,3-unsaturated
sugar and (c) glycosylation using 2,3-unsaturated-4-keto sugar.
Scheme 1 Synthesis of 2,3-unsaturated glycosyl acetate 1, 2,3-dideoxy glycosyl acetate 2, and 2,3-unsaturated-4-keto glycosyl acetate 3a a Reagents and
conditions: (a) BzCl, Py, 0 ◦C, 0.5 h, 100%; (b) Ac2O, H2SO4, -40 ◦C, 0.5 h, 70%; (c) H2, cat. Rh/Al2O3, EtOAc–PhMe (9/1), 0 ◦C, 1 h, 86%; (d) BzCl,
Py, CH2Cl2, -78 ◦C, 2 h, 85%; (e) PDC, CH2Cl2, 25 ◦C, 18 h, 84%; (f) CAN, MeCN–H2O (9/1), 25 ◦C, 1.5 h, 94%; (g) AcCl, Py, CH2Cl2, 25 ◦C, 1.5 h,
73% (a : b = 89 : 11).
2,3-unsaturated-4-keto glycosyl acetate 3 were effectively synthe-
sized from 2,3-unsaturated glycosides 414 and 5,15 which were read-
ily prepared from glucal via Ferrier-rearrangement reactions.16
Thus, 4 was protected with benzoyl groups using benzoyl chloride
in pyridine, then subjected to acetolysis using acetic anhydride
and H2SO4 (conc.) to give 2,3-unsaturated glycosyl acetate 1
via 6 in a high overall yield. At this stage, 1H-NMR analysis
confirmed that 1 adopts a half-chair conformation based on
coupling constants between H1 and H2 (2.1 Hz), H2 and H3
(10.2 Hz), and H3 and H4 (1.5 Hz). Benzoyl-protected 2,3-dideoxy
glycosyl acetate 2 was effectively prepared by hydrogenation of 1
using Rh/Al2O3 as a catalyst.17 In contrast, the acetolysis of methyl
glycosides that possess a 2,3-unsaturated-4-keto skeleton was
ineffective, and therefore, 2,3-unsaturated-4-keto glycosyl acetate
3 was synthesized from 2,3-unsaturated glycoside 5 in four steps:
1) regioselective benzoylation of the C6 hydroxy group of 5, 2)
oxidation of the C4 hydroxy group of 7 using PDC, 3) deprotection
of the p-methoxyphenyl (MP) group at the C1-position of 8 using
CAN, and 4) acetylation at the C1-position of 9 using AcCl in
pyridine.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 3164–3178 | 3165
©

View Article Online
Table 1 Competitive glycosylations using 1 and 2
Entrya
Donor
Activator (equiv.)
Temp./oC
Time/h
Glycoside yield (%) b (a : b ratio)b
Recovery yield of donor (%)b
1
2
3
4
5
6
7
8
9
1
1
1
1
1
2
2
2
2
2
TMSOTf (0.3)
TBSOTf (0.3)
BF3-OEt2 (1.0)
TfOH (0.5)
-78
-70
-60
-70
0
-78
-70
-60
-70
0
3
3
24
24
96
3
11: 89 (69 : 31)
11: 91 (68 : 32)
11: 72 (80 : 20)
11: 85 (80 : 20)
11: 80 (56 : 44)
12: 5 (60 : 40)
12: 4 (58 : 42)
12: 3 (67 : 33)
12: 10 (60 : 40)
12: 4 (35 : 65)
1: 0
1: 0
1: 13
1: 5
1: 9
2: 89
2: 91
2: 90
2: 85
2: 87
MK-10c
TMSOTf (0.3)
TBSOTf (0.3)
BF3-OEt2 (1.0)
TfOH (0.5)
3
24
24
96
10
MK-10c
a The ratio between glycosyl donor and glycosyl acceptor was 1.0 : 0.9. b Yields and a : b ratios were determined by HPLC analysis. c 100 wt% of MK-10
(relative to donor) to donor was used.
Reactivities and chemoselectivities for the glycosylations of 1–3
glycosyl acetate 14, which are the C4-epimers of 1 and 2,
respectively, resulted in the preferential formation of disaccharide
15 over 16. Based on these results, the chemoselective phenomenon
was shown to be independent of the configuration of the hydroxyl
group of the glycosyl donors. Furthermore, it was confirmed that
these chemoselectivities were highly independent of the examined
solvents, such as CH2Cl2, PhMe, THF, and ether. Thus, the
chemoselective activations of the 2,3-unsaturated glycosyl donors
were effectively realized in these solvents by controlling the
reaction temperature appropriately.
Based on these favorable results, we turned our attention
to investigate the relative reactivities of 2,3-unsaturated versus
2,3-unsaturated-4-keto glycosyl donors. Accordingly, competitive
glycosylations were carried out using 2,3-unsaturated glycosyl
donor 1 (1.0 equiv.) or 2,3-unsaturated-4-keto glycosyl donor 3
(1.0 equiv.) and glycosyl acceptor 10 (1.0 equiv.) under several
conditions. As shown in Table 2, disaccharide 11 was generated
from 1 and 10 in high yields using TMSOTf, TBSOTf, BF3·OEt2,
TfOH, or montmorillonite K-10 (MK-10) as the activator (entries
1–5). In contrast, the formation of disaccharide 17 using 3 and 10
(entries 6–10), under similar conditions, was unsuccessful; again,
the starting material 3 was recovered in high yield. These results
To confirm our hypothesis, competitive glycosylations were carried
out using either 2,3-unsaturated glycosyl donor 1 (1.0 equiv.) or
2,3-dideoxy glycosyl donor 2 (1.0 equiv.) and glycosyl acceptor
10 (0.9 equiv.) under several conditions. As listed in Table 1,
the glycosylations were carried out using TMSOTf, TBSOTf,
BF3·OEt2, TfOH, or montmorillonite K-10 (MK-10) as activators.
As expected, the activation of 1 afforded disaccharide 11 in
high yields (entries 1–5). Under similar conditions, however, the
activation of 2 did not provide disaccharide 12 (entries 6–10) – in
fact, unreacted glycosyl donor 2 was recovered in high yields. These
results clearly show that the 2,3-unsaturated glycosyl donors,
which mimic the mechanism of the lysozyme hydrolysis reaction,
are much more reactive than the corresponding 2,3-dideoxy
glycosyl donors. This tendency was essentially independent of
the glycosylation activator. Furthermore, a one-flask competitive
glycosylation using both donors (1, 1.0 equiv.; 2, 1.0 equiv.) and
acceptor (10, 0.9 equiv.) (TMSOTf, MS 5A, CH2Cl2, -78 ◦C, 3 h)
resulted in the preferential formation of 11 (91%, a : b = 70 : 30)
over 12 (0%). Similarly, as shown in Fig. 2, the glycosylations of
10 and of 2,3-unsaturated glycosyl acetate 13 and 2,3-dideoxy
Fig. 2 Competitive glycosylations using 13 and 14.
3166 | Org. Biomol. Chem., 2010, 8, 3164–3178 This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Table 2 Competitive glycosylations using 1 and 3
Entrya
Donor
Activator (equiv.)
Temp/oC
Time/h
Glycoside yield (%) b (a : b ratio)c
Recovery yield of donor (%)b
1
2
3
4
5
6
7
8
9
1
1
1
1
1
3
3
3
3
3
TMSOTf (0.3)
TBSOTf (0.3)
BF3-OEt2 (2.0)
TfOH (0.3)
-60
-50
-60
-50
0
-60
-50
-60
-50
0
1
1
48
0.75
8
1
1
48
0.75
8
11: 100 (66 : 34)
11: 92 (70 : 30)
11: 83 (76 : 24)
11: 92 (69 : 31)
11: 95 (64 : 36)
17: 0
17: 8 (63 : 37)
17: 2 (77 : 23)
17: 5 (76 : 24)
17: 8 (74 : 26)
1: 0
1: 0
1: 8
1: 0
MK-10d
1: 0
TMSOTf (0.3)
TBSOTf (0.3)
BF3-OEt2 (2.0)
TfOH (0.3)
3: 95
3: 83
3: 95
3: 94
3: 87
10
MK-10d
a The ratio of glycosyl donor to glycosyl acceptor was 1.0 : 1.0. b Isolated yields. c a : b ratios were determined by 1H-NMR analysis. d 100 wt% of MK-10
(relative to donor) was used.
Table 3 Competitive glycosylations using 18 and 3
Entrya
Donor
Activator (equiv.)
Temp/oC
Time/h
Glycoside yield (%) b (a : b ratio)c
Recovery yield of donor (%)b
1
2
3
4
5
6
7
8
9
18
18
18
18
18
3
TMSOTf (0.3)
TBSOTf (0.3)
BF3-OEt2 (2.0)
TfOH (0.3)
-50
-45
-50
-45
25
-50
-45
-50
-45
25
1
1
36
1
25
1
1
36
1
19: 99 (68 : 32)
19: 98 (68 : 32)
19: 94 (69 : 31)
19: 96 (73 : 27)
19: 84 (68 : 32)
17: 0
17: 4 (66 : 34)
17: 6 (81 : 19)
17: 4 (84 : 16)
17: 0
18:0
18:0
18:0
18:0
18:9
3: 91
3: 96
3: 93
3: 91
3: 91
MK-10d
TMSOTf (0.3)
TBSOTf (0.3)
BF3-OEt2 (2.0)
TfOH (0.3)
3
3
3
10
3
MK-10d
25
a The ratio between glycosyl donor and glycosyl acceptor was 1.0 : 1.0. b Isolated yields. c a : b ratios were determined by 1H-NMR analysis. d 100 wt% of
MK-10 (relative to donor) was used.
clearly indicate that the 2,3-unsaturated glycosyl donor is more
reactive than the corresponding 2,3-unsaturated-4-keto glycosyl
donor. Similarly, a one-flask competitive glycosylation using 1
(1.0 equiv.), 3 (1.0 equiv.), and 10 (1.0 equiv.) (TMSOTf, MS 5A,
CH2Cl2, -60 ◦C, 1 h) resulted in the preferential formation of 11
(93%, a : b = 67 : 33) over 17 (3%, a : b = 64 : 36).
glycosyl donor 3 (1.0 equiv.), and glycosyl acceptor 10 (1.0 equiv.)
under various conditions. Although the reactivity of 2 was found
to be slightly higher than that of 3, the difference was insignificant
in terms of chemoselective glycosylation. It has been reported that
protection using an acyl group generally decreases the reactivity
of the glycosyl donor.18 Accordingly, to improve the reactivity,
competitive glycosylation was carried out using 2,3-dideoxy
glycosyl donor 18 (1.0 equiv.), which, instead of benzoyl, has a
benzyl protecting group at the C4-position. As shown in Table 3,
disaccharide 19 was formed from 18 and 10 in high yields using
TMSOTf, TBSOTf, BF3·OEt2, TfOH, or montmorillonite K-10
(MK-10) as the activator (entries 1–5). Under similar conditions,
insignificant amounts of disaccharide 17 were generated from 3
and 10 (entries 6–10), in which 3 was recovered in high yield. These
Next, the comparative reactivities between 2,3-dideoxy and
2,3-unsaturated-4-keto glycosyl donors, both which can serve
as the disarmed analog of 2,3-unsaturated glycosyl donors,
were investigated. Because the conformations and the electronic
characteristics of the glycosyl donors differ significantly, it was
difficult to predict which donor would exhibit higher reactivity.
We therefore first conducted competitive glycosylations using
2,3-dideoxy glycosyl donor 2 (1.0 equiv.), 2,3-unsaturated-4-keto
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 3164–3178 | 3167
©

View Article Online
results clearly indicate that the 2,3-dideoxy glycosyl donor is more
reactive than the corresponding 2,3-unsaturated-4-keto glycosyl
donor, and that the difference in reactivity between these glycosyl
donors can be enhanced by choosing the optimal protecting group
at the C4-position of the 2,3-dideoxy glycosyl donor. Finally, the
one-flask competitive glycosylation between 18 (1.0 equiv.) and
3 (1.0 equiv.) with 10 (1.0 equiv.) (TMSOTf, MS 5A, CH2Cl2,
charides are found, for example, in the angucycline group of
antibiotics as acurose-rhodinose disaccharides.19 As shown in
Scheme 2(a), desired disaccharide 21 was obtained in a high yield
with a-stereoselectivity via chemoselective glycosylation using
TMSOTf at -80 ◦C for 0.5 h. In contrast, oligosaccharide(s)
that would result from the undesirable activation of 20 (which
would lead to self-condensation) was not detected. Disaccharide
21 possesses an acetate leaving group at the C1-position, without
epimerization. Furthermore, the reaction between disaccharide 21
and acceptor 10 proceeded smoothly using TMSOTf at -40 ◦C
for 0.5 h in PhMe to afford trisaccharide 22 in a high yield
with a-stereoselectivity. The use of PhMe as the solvent in the
second glycosylation reaction was found to be highly effective
in preventing the cleavage of the first glycosidic bond, and in
increasing the a-stereoselectivity. Based on these results, the
combination of the 2,3-unsaturated and the corresponding 2,3-
dideoxy glycosyl donors can define a new family of armed and
disarmed glycosyl donors, respectively.
◦
-50 C, 1 h) demonstrated a preference toward 19 (99%, a : b =
71 : 29) over 17 (0%).
Chemoselective glycosylations for the synthesis of
deoxyoligosaccharides
Consequently, chemoselective glycosylations were investigated
using 2,3-unsaturated, 2,3-unsaturated-4-keto, and 2,3-dideoxy
sugars. First, the glycosylation between 2,3-unsaturated glycosyl
acetate 1 (glycosyl donor) and 2,3-dideoxy glycosyl acetate 20
(glycosyl acceptor) was carried out. Hex-2-enosyl-hexose disac-
Scheme 2 Synthesis of trisaccharides by chemoselective glycosylations using 2,3-unsaturated, 2,3-dideoxy, and 2,3-unsaturated-4-keto sugars
3168 | Org. Biomol. Chem., 2010, 8, 3164–3178 This journal is The Royal Society of Chemistry 2010
©

View Article Online
Next, as shown in Scheme 2(b), chemoselective glycosylation
between 2,3-unsaturated glycosyl acetate 1 (glycosyl donor) and
2,3-unsaturated-4-keto glycosyl acetate 23 (glycosyl acceptor)
proceeded smoothly using TMSOTf at -75 ◦C for 0.5 h to give
desired disaccharide 24 in a high yield with a-stereoselectivity.
Furthermore, disaccharide 24, which possesses an acetate leaving
group at the C1-position, reacted with glycosyl acceptor 10 using
TMSOTf at -40 ◦C for 0.5 h to afford trisaccharide 25 in a
high yield with a-stereoselectivity. In this case, 2,3-unsaturated
and the corresponding 2,3-unsaturated-4-keto glycosyl donors can
define another new family of armed and disarmed glycosyl donors,
respectively.
As shown in Scheme 2(c), chemoselective glycosylation be-
tween 2,3-dideoxy glycosyl acetate 18 (glycosyl donor) and
2,3-unsaturated-4-keto glycosyl acetate 23 (glycosyl acceptor)
using TMSOTf at -50 ◦C for 1 h afforded disaccharide 26 in
a high yield with a-stereoselectivity; the disaccharide further
gave tirsaccharide 27 via glycosylation with 10 using TMSOTf at
-35 ◦C for 0.5 h. In this case, 2,3-dideoxy and the corresponding
2,3-unsaturated-4-keto glycosyl donors function as the armed and
disarmed glycosyl donors, respectively.
When 2,3,6-trideoxy glycosyl donor 37 was used instead of 33 for
the glycosylation of 28, activation of the donor was not observed
below 0 C in the presence of Yb(OTf)3. When the reaction was
◦
carried out at 0 to 25 ◦C, as shown in Fig. 3(c), the corresponding
glycoside 38 was obtained in a yield of merely 22%, accompanied
by considerable amounts of by-products. These results clearly
indicate that glycosylations involving 2,3-unsaturated glycosyl
donors proceed under conditions that are considerably milder than
usual, and can be used in the effective construction of O-glycosidic
linkages, even for tertiary alcohols with low nucleophilicity.
Conclusions
In the present studies, we have designed 2,3-unsaturated glycosyl
donors that mimic the distinctive features of the regioselective
hydrolysis reaction of lysozyme. We found that 2,3-unsaturated
glycosyl donors exhibit high reactivity, while the corresponding
2,3-unsaturated-4-keto glycosyl donors show low reactivity, under
several glycosylation conditions. Our results have helped establish
2,3-unsaturated and 2,3-unsaturated-4-keto glycosyl donors as
a new family of armed and disarmed glycosyl donors, re-
spectively. Furthermore, chemoselective glycosylations via com-
binatorial uses of 2,3-unsaturated, 2,3-unsaturated-4-keto, and
2,3-dideoxy glcosyl donors can effectively provide various types
of deoxyoligosaccharides in short-steps. We have further shown
that 2,3-unsaturated glycosyl donors can be employed in the
challenging construction of O-glycosides of unreactive alcohols.
Our novel glycosylation methodology, therefore, can be widely
applicable towards the efficient synthesis of biologically important
natural products, including several antitumor antibiotics that
possess 2,3-dideoxy, 2,3-unsaturated, and/or 2,3-unsaturated-4-
keto sugar(s).21 Investigations to widen the applicability of our
glycosylation method are currently underway in our laboratories.22
Efficient glycosylations of 2,3-unsaturated glycosyl acetates with
tertiary alcohols
Finally, we examined the reaction between highly reactive
2,3-unsaturated glycosyl donors and unreactive alcohols, such
as tertiary alcohols, towards the construction of glycosides. The
formation of O-glycosidic linkages between tertiary alcohols and
highly deoxygenated sugars remains challenging for two reasons:
1) tertiary alcohols have a tendency to generate carbocations,
along with elimination of a hydroxyl group under acidic condi-
tions; and 2) because of the low nucleophilicity of tertiary alcohols,
the active species—an oxocarbenium intermediate generated from
a glycosyl donor—is easily converted to the corresponding glycal
via deprotonation at the C2-position. Our glycosylation method,
in contrast, succeeds in overcoming these problems because 2,3-
unsaturated glycosyl donors can be activated under much milder
acidic conditions than that for the corresponding 2,3-dideoxy
glycosyl donors. Furthermore, the absence of a b-proton at the
cationic center of the oxocarbenium ion prevents the side reaction
mentioned above.
Accordingly, as shown in Fig. 3(a), the glycosylations of
adamantan-1-ol (28) and tert-butanol (29) with an almost
equal amount of 2,3-unsaturated glycosyl acetate 30 pro-
ceeded effectively in the presence of a very mild Lewis acid,
Yb(OTf)3,20 at 0 ◦C to give glycosides 31 and 32, respec-
tively, in high yields. For the glycosylations using 33, whose
a-glycosides can readily be converted into naturally occurring
L-rhodinosides, L-acurosides, L-cinerulosides, and L-rhamnosides
by appropriate reduction and/or oxidation,12c the corresponding
glycosides 34 and 35 were also obtained in good to high yields
with excellent a-stereoselectivities. In contrast, when glycal 36,
which is the synthetic equivalent of 30 and can be converted into
31 and 32 by Ferrier rearrangement, was used as the glycosyl
donor for the glycosylation of 28, the reaction did not proceed,
under identical conditions as those for 30. Likewise, as shown in
Fig. 3(b), the glycosylation between 2,3-dideoxy glycosyl donor 18
and 28, under the same conditions as used for 30, did not proceed.
Experimental section
General method for chemical synthesis
Melting points were determined on a micro hot-stage (Yanako
MP-S3) and were uncorrected. Optical rotations were measured on
a JASCO DIP-370 photo-electric polarimeter. NMR spectra were
recorded on a Varian MVX-300 (300 or 75 MHz) spectrometer
using tetramethylsilane as internal standard unless otherwise
noted. ESI-TOF Mass spectra were measured on a Waters LCT
premier XE. Silica gel TLC and column chromatography were
performed on Merck TLC 60F-254 (0.25 mm) and Silica Gel
60 N (spherical, neutral) (Kanto Chemical Co., Inc.), respectively.
Air- and/or moisture-sensitive reactions were carried out under
an atmosphere of argon using oven-dried glassware. In general,
organic solvents were purified and dried using an appropriate
procedure, and evaporation and concentration were carried out
under reduced pressure below 30 ◦C, unless otherwise noted. The
configurations at the anomeric positions of the 2,3-unsaturated
glycosides were determined by the 1H-NMR analyses of the
corresponding 2,3-dideoxy glycosides which were obtained by
standard hydrogenations of the double bond in the 2,3-unsaturated
glycosides using H2 and 10% Pd/C. On the other hand, the
configurations at the anomeric positions of the 2,3-unsaturated-
4-keto glycosides were determined by the 1H-NMR analyses
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 3164–3178 | 3169
©

View Article Online
Fig. 3 Glycosylations of 2,3-unsaturated glycosyl acetates and tertiary alcohols.
73.9 ◦C (Et2O–hexane); Rf 0.37 (3/1 hexane–EtOAc); [a]2D2 +193.2
(c 1.27, CHCl3); H NMR (CDCl3, TMS) d 8.07-7.99 (4H, m,
of the corresponding 2,3-dideoxy glycosides which were ob-
tained by standard hydrogenations of the double bond in the
2,3-unsaturated-4-keto glycosides using H2 and 10% Pd/C, fol-
lowed by stereoselective reductions of the ketone group in the
resulting 2,3-dideoxy-4-keto glycosides using NaBH4.12c
1
ArH), 7.61-7.51 (2H, m, ArH), 7.47-7.37 (4H, m, ArH), 6.05 (1H,
br-ddd, J2,3 = 10.0 Hz, J3,4 = 1.5 Hz, H-3), 5.92 (1H, ddd, J2,3
10.0 Hz, J2,4 = 2.0 Hz, J1,2 = 2.0 Hz, H-2), 5.70 (1H, ddd, J4,5
9.0 Hz, J2,4 = 2.0 Hz, J3,4 = 1.5 Hz, H-4), 5.00 (1H, br-dd, J1,2
=
=
=
2.0 Hz, H-1), 4.59 (1H, dd, J6,6 = 11.7 Hz, J5,6 = 2.4 Hz, H-6),
4.47 (1H, dd, J6,6 = 11.7 Hz, J5,6 = 5.7 Hz, H-6), 4.43 (1H, ddd,
J4,5 = 9.0 Hz, J5,6 = 5.7 Hz, J5,6 = 2.4 Hz, H-5), 3.49 (3H, s, OMe);
Anal. Calcd for C21H20O6: C, 68.47; H, 5.47. Found: C, 68.51; H,
5.62.
Methyl 4,6-di-O-benzoyl-2,3-dideoxy-a-D-erythro-hex-2-
enopyranoside (6)
To
a
solution of methyl 2,3-dideoxy-a-D-erythro-hex-2-
enopyranoside (4) (5.00 g, 31.2 mmol) in dry pyridine (50.0 ml)
was added benzoyl chloride (11.5 mL, 93.6 mmol) under ice-
bath cooling. After the mixture was stirred at 0 ◦C for 30 min,
the reaction was quenched by addition of water (100 mL). The
resulting mixture was extracted with EtOAc (100 mL ¥ 3). The
combined organic layer was washed with brine (100 mL), dried
over anhydrous Na2SO4, and concentrated in vacuo. Purification
of the residue by silica-gel column chromatography (hexane–
EtOAc = 5/1) gave 6 (11.5 g, quant.). White needles; m.p. 73.2 -
4,6-Di-O-benzoyl-2,3-dideoxy-a-D-erythro-hex-2-enopyranosyl
acetate (1)
To a solution of 6 (3.00 g, 8.14 mmol) in Ac2O (60.0 ml)
was dropwisely added concd H2SO4 (0.434 mL, 8.14 mmol) at
-40 ◦C. After the mixture was stirred at the temperature for
30 min, NaOAc (1.34 g, 16.3 mmol) was added. The mixture
3170 | Org. Biomol. Chem., 2010, 8, 3164–3178
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
was poured into water (100 mL), and the resulting mixture was
extracted with EtOAc (100 mL ¥ 3). The combined organic layer
was washed with brine (100 mL), dried over anhydrous Na2SO4,
and concentrated in vacuo. Purification of the residue by silica-
gel column chromatography (chloroform–EtOAc/TEA = 98/2/5)
gave 1 (2.26 g, 70%). Colorless syrup; Rf 0.63 (1/1 hexane–EtOAc);
[a]2D9 +120.1 (c 2.08, CHCl3); 1H NMR (CDCl3, TMS) d 8.06-7.96
(4H, m, ArH), 7.62-7.49 (2H, m, ArH), 7.47-7.34 (4H, m, ArH),
6.39 (1H, d, J1,2 = 2.1 Hz, H-1), 6.19 (1H, ddd, J2,3 = 10.2 Hz,
J3,4 = 1.5 Hz, H-3), 5.94 (1H, ddd, J2,3 = 10.2 Hz, J2,4 = 2.7 Hz,
J1,2 = 2.1 Hz, H-2), 5.75 (1H, ddd, J4,5 = 9.3 Hz, J2,4 = 2.7 Hz,
J3,4 = 1.5 Hz, H-4), 4.62 (1H, dd, J6,6 = 11.1 Hz, J5,6 = 2.7 Hz,
H-6), 4.46 (1H, dd, J6,6 = 11.1 Hz, J5,6 = 5.7 Hz, H-6), 4.43 (1H,
ddd, J4,5 = 9.3 Hz, J5,6 = 5.7 Hz, J5,6 = 2.7 Hz, H-5), 2.11 (3H, s,
OAc); Anal. Calcd for C22H20O7: C, 66.66; H, 5.09. Found: C,
66.73; H, 5.14.
p-Methoxyphenyl 6-O-benzoyl-2,3-dideoxy-a-D-glycelo-hex-2-
enopyranos-4-uloside (8)
To a solution of 7 (518 mg, 1.46 mmol) in dry CH2Cl2 (10.4 mL)
was added pyridinium dichromate (2.74 g, 7.27 mmol) under Ar
atmosphere. After the mixture was stirred at room temperature
(25 ◦C) for 18 h, the mixture was filtrated through celite pad.
The filtrate was concentrated in vacuo. Purification of the residue
by silica-gel column chromatography (0→50% EtOAc in hexane)
gave 8 (430 mg, 84%). Pale yellow solids; m.p. 98.6–99.0 ◦C; Rf
0.40 (2/1 hexane–EtOAc); [a]3D3 +63.9 (c 0.87, CHCl3); 1H NMR
(CDCl3, TMS) d 7.94 (2H, dd, Jo,m = 8.1 Hz, Jo,p = 1.2 Hz, Ho of
Bz), 7.56 (1H, tt, Jm,p = 7.5 Hz, Jo,p = 1.2 Hz, Hp of Bz), 7.41 (2H,
dd, Jo,m = 8.1 Hz, Jm,p = 7.5 Hz, Hm of Bz), 7.07 & 6.75 (4H, m,
ArH), 7.07 (1H, dd, J2,3 = 10.2 Hz, J1,2 = 3.6 Hz, H-2), 6.29 (1H,
d, J2,3 = 10.2 Hz, H-3), 5.54 (1H, d, J1,2 = 3.6 Hz, H-1), 4.99 (1H,
dd, J5,6 = 6.6 Hz, J5,6 = 3.0 Hz, H-5), 4.84 (1H, dd, J6,6 = 12.3 Hz,
J5,6 = 3.0 Hz, H-6), 4.68 (1H, dd, J6,6 = 12.3 Hz, J5,6 = 6.6 Hz,
H-6), 3.75 (3H, s, OMe); Anal. Calcd for C20H18O6: C, 67.79; H,
5.12. Found: C, 67.58; H, 5.20.
4,6-Di-O-benzoyl-2,3-dideoxy-a-D-erythro-hexopyranosyl acetate
(2)
A suspension of 1 (20.0 mg) and 5% Rh/Al2O3 (2.0 mg) in EtOAc–
toluene (9/1, v/v, 1.00 mL) was stirred under H2 atmosphere
(balloon). After the suspension was stirred at 0 ◦C for 1 h, it
was filtered through celite pad. The filtrate was concentrated
in vacuo. Purification of the residue by flash silica-gel column
chromatography (hexane/acetone = 3/1) gave 2 (17.2 mg, 86%).
White needles; m.p. 102.5–102.9 ◦C; Rf 0.43 (2/1 hexane–EtOAc);
[a]3D0 +138.5 (c 1.04, CHCl3); 1H NMR (CDCl3, TMS) d 8.06-7.97
(4H, m, ArH), 7.60-7.50 (2H, m, ArH), 7.47-7.36 (4H, m, ArH),
6-O-Benzoyl-2,3-dideoxy-D-glycelo-hex-2-enopyranos-4-ulose (9)
To a solution of 8 (392 mg, 1.11 mmol) in aq. acetonitrile
(acetonitrile–water = 9/1, 3.92 mL) was added cerium(IV) am-
monium nitrate (1.51 g, 2.76 mmol). After the mixture was stirred
at room temperature (25 ◦C) for 1 h, the mixture was poured into
water (3 mL), and extracted with EtOAc (3 mL ¥ 4). After the
combined organic layer was washed with brine (3 mL), dried over
anhydrous Na2SO4, and concentrated in vacuo. Purification of the
residue by silica-gel column chromatography (0→60% EtOAc in
hexane) gave 9 as a mixture of anomers (259 mg, 94%, a : b =
6.21 (1H, br-dd, H-1), 5.18 (1H, ddd, J4,5 = J3,4 = 10.2 Hz, J3,4
=
4.8 Hz, H-4), 458 (1H, dd, J6,6 = 11.7 Hz, J5,6 = 2.7 Hz, H-6), 4.40
(1H, dd, J6,6 = 11.7 Hz, J5,6 = 5.1 Hz, H-6), 4.32 (1H, ddd, J4,5
=
1
75 : 25). Yellow solids; Rf 0.36 (1/1 hexane–EtOAc); H NMR
10.2 Hz, J5,6 = 5.1 Hz, J5,6 = 2.7 Hz, H-5), 2.34-2.23 (1H, m),
2.15 (3H, s, OAc), 2.10-1.90 (3H, m); Anal. Calcd for C22H22O7:
C, 66.32; H, 5.57. Found: C, 66.25; H, 5.55.
(CDCl3, TMS), a isomer (9a): d 8.05-7.98 (2H, m, ArH), 7.58-
7.53 (1H, m, ArH), 7.46-7.39 (2H, m, ArH), 6.96 (1H, dd, J2,3
=
10.5 Hz, J1,2 = 0.7 Hz, H-2), 6.23 (1H, d, J2,3 = 10.5 Hz, H-3), 5.73
(1H, br-d, J = 3.2 Hz, H-1), 4.96 (1H, dd, J5,6 = 5.1 Hz, J5,6
=
2.6 Hz, H-5), 4.83 (1H, dd, J6,6 = 11.9 Hz, J5,6 = 2.6 Hz, H-6),
4.71 (1H, dd, J6,6 = 11.9 Hz, J5,6 = 5.1 Hz, H-6), 3.15 (1H, m,
OH); b isomer (9b): 8.05-7.98 (2H, m, ArH), 7.58-7.53 (1H, m,
p-Methoxyphenyl 6-O-benzoyl-2,3-dideoxy-a-D-erythro-hex-2-
enopyranoside (7)
To a solution of p-methoxyphenyl 2,3-dideoxy-a-D-erythro-hex-2-
enopyranoside (5) (152 mg, 0.602 mmol) in dry CH2Cl2 (3.04 mL)
was added pyridine (107 mL, 1.33 mmol) and benzoyl chloride
(76.3 mL, 0.663 mmol) at -78 ◦C under Ar atmosphere. After the
mixture was stirred at the temperature for 2 h, the mixture was
poured into water (4 mL), and extracted with EtOAc (3 mL ¥ 4).
The combined organic layer was washed with brine (4 mL), dried
over anhydrous Na2SO4, and concentrated in vacuo. Purification of
the residue by silica-gel column chromatography (0→50% EtOAc
in hexane) gave 7 (182 mg, 85%). White solids; m.p. 96.3–96.9 ◦C;
Rf 0.45 (1/1 hexane–EtOAc); [a]3D2 +71.9 (c 0.92, CHCl3); 1H NMR
(CDCl3, TMS) d 7.96 (2H, dd, Jo,m = 8.1 Hz, Jo,p = 0.9 Hz, Ho
of Bz), 7.56 (1H, tt, Jm,p = 7.5 Hz, Jo,p = 0.9 Hz, Hp of Bz), 7.40
(2H, dd, Jo,m = 8.1 Hz, Jm,p = 7.5 Hz, Hm of Bz), 7.05 & 6.76 (4H,
ArH), 7.46-7.39 (2H, m, ArH), 7.01 (1H, dd, J2,3 = 10.5 Hz, J1,2
=
2.0 Hz, H-2), 6.26 (1H, m, H-1), 6.23 (1H, d, J2,3 = 10.5 Hz, H-3),
4.81 (1H, dd, J6,6 = 11.9 Hz, J5,6 = 1.7 Hz, H-6), 4.74 (1H, dd,
J6,6 = 11.9 Hz, J5,6 = 3.2 Hz, H-6), 4.56 (1H, m, H-5), 3.15 (1H,
m, OH); Anal. Calcd for C13H12O5: C, 62.90; H, 4.87. Found: C,
62.69; H, 4.94.
6-O-Benzoyl-2,3-dideoxy-a-D-glycelo-hex-2-enopyranos-4-ulosyl
acetate (3)
To a solution of 9 (1.186 g, 4.78mmol) indryCH2Cl2 (23.7 mL) was
added pyridine (850 mL, 10.5 mmol) and acetyl chloride (510 mL,
7.17 mmol) under Ar atmosphere and ice-bath cooling. After
the mixture was stirred for 1.5 h at room temperature (25 ◦C),
the mixture was poured into water (150 mL), and extracted with
EtOAc (100 mL ¥ 4). The combined organic layer was washed with
brine (150 mL), dried over anhydrous Na2SO4, and concentrated
in vacuo. Purification of the residue by flash silica-gel column
chromatography (chloroform/acetone = 50/1) gave 3a (0.89 g,
65%) and 3b (0.11 g, 8%). a isomer (3a): Pale yellow syrup; Rf
m, ArH), 6.12 (1H, br-d, J = 9.9 Hz, H-3), 5.95 (1H, ddd, J2,3
=
9.9 Hz, J1,2 = J2,4 = 2.1 Hz, H-2), 5.58 (1H, m, H-1), 4.73 (1H, dd,
J6,6 = 12.0 Hz, J5,6 = 5.4 Hz, H-6), 4.52 (1H, dd, J6,6 = 12.0 Hz,
J5,6 = 2.1 Hz, H-6), 4.22-4.10 (2H, m, H-4 & H-5), 3.75 (3H, s,
OMe), 2.33 (1H, d, J4,OH = 6.9 Hz, OH); Anal. Calcd for C20H20O6:
C, 67.41; H, 5.66. Found: C, 67.18; H, 5.70.
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 3164–3178 | 3171
©

View Article Online
0.28 (2/1 hexane–EtOAc); [a]3D2 -148.4 (c 0.87, CHCl3); 1H NMR
(CDCl3, TMS) d 7.98 (2H, dd, Jo,m = 8.5 Hz, Jo,p = 1.5 Hz, Ho of
Bz), 7.56 (1H, tt, Jm,p = 7.3 Hz, Jo,p = 1.5 Hz, Hp of Bz), 7.42 (2H,
Methyl 6-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-b-D-erythro-hex-2-
nopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (11b)
Colorless syrup; Rf 0.73 (1/1 hexane–EtOAc); [a]3D0 +104.5 (c 1.95,
CHCl3); 1H NMR (CDCl3, TMS) d 8.04-7.96 (4H, m, ArH), 7.61-
dd, Jo,m = 8.5 Hz, Jm,p = 7.3 Hz, Hm of Bz), 6.99 (1H, dd, J2,3
=
10.2 Hz, J1,2 = 3.6 Hz, H-2), 6.59 (1H, d, J1,2 = 3.6 Hz, H-1), 6.32
7.46 (2H, m, ArH), 7.46-7.22 (19H, m, ArH), 6.10 (1H, ddd, J2¢,3¢
10.2 Hz, J3¢,4¢ = 3.6 Hz, J1¢,3¢ = 1.5 Hz, H-3¢), 5.92 (1H, ddd, J2¢,3¢
10.2 Hz, J1¢,2¢ = 1.5 Hz, J2¢,4¢ = 1.5 Hz, H-2¢), 5.55 (1H, ddd, J4¢,5¢
11.4 Hz, J3¢,4¢ = 3.6 Hz, J1¢,3¢ = 1.5 Hz, H-4¢), 5.16 (1H, dd, J1¢,2¢
=
=
=
=
(1H, d, J2,3 = 10.2 Hz, H-3), 4.86 (1H, dd, J5,6 = 4.8 Hz, J5,6
=
3.0 Hz, H-5), 4.80 (1H, dd, J6,6 = 12.0 Hz, J5,6 = 3.0 Hz, H-6), 4.71
(1H, dd, J6,6 = 12.0 Hz, J5,6 = 4.8 Hz, H-6), 2.15 (3H, s, OAc); Anal.
Calcd for C15H14O6: C, 62.07; H, 4.86. Found: C, 61.77; H, 4.95.
b isomer (3b): Pale yellow syrup; Rf 0.28 (2/1 hexane–EtOAc);
[a]3D2 +49.5 (c 1.61, CHCl3); 1H NMR (CDCl3, TMS) d 8.01 (2H,
1.5 Hz, J1¢,3¢ = 1.5 Hz, H-1¢), 4.98 & 4.80 (2H, ABq, J = 11.1 Hz,
ArCH2), 4.87 & 4.61 (2H, ABq, J = 11.1 Hz, ArCH2), 4.78 & 4.66
(2H, ABq, J = 12.0 Hz, ArCH2), 4.59 (1H, d, J1,2 = 3.6 Hz, H-1),
4.54 (1H, dd, J6¢,6¢ = 11.7 Hz, J5¢,6¢ = 6.0 Hz, H-6¢), 4.49 (1H, dd,
J6¢,6¢ = 11.7 Hz, J5¢,6¢ = 5.4 Hz, H-6¢), 4.31 (1H, ddd, J4¢,5¢ = 11.4 Hz,
J5¢,6¢ = 6.0 Hz, J5¢,6¢ = 5.4 Hz, H-5¢), 4.08-4.01 (1H, m, H-6), 3.97
(1H, dd, J2,3 = J3,4 = 9.3 Hz, H-3), 3.79-3.71 (2H, m, H-5 & H-6),
3.57 (1H, dd, J3,4 = J4,5 = 9.3 Hz, H-4), 3.53 (1H, dd, J2,3 = 9.3 Hz,
J1,2 = 3.6 Hz, H-2), 3.30 (3H, s, OMe); Anal. Calcd for C48H48O11:
C, 71.98; H, 6.04. Found: C, 71.71; H, 6.15.
dd, Jo,m = 8.7 Hz, Jo,p = 0.9 Hz, Ho of Bz), 7.57 (1H, tt, Jm,p
=
7.5 Hz, Jo,p = 0.9 Hz, Hp of Bz), 7.43 (2H, dd, Jo,m = 8.7 Hz, Jm,p
=
7.5 Hz, Hm of Bz), 6.94 (1H, dd, J2,3 = 10.5 Hz, J1,2 = 3.0 Hz,
H-2), 6.61 (1H, dd, J1,2 = 3.0 Hz, J1,3 = 1.2 Hz, H-1), 6.37 (1H,
dd, J2,3 = 10.2 Hz, J1,3 = 1.2 Hz, H-3), 4.75-4.66 (3H, m, H-5 &
H-6 ¥ 2), 1.99 (3H, s, OAc); Anal. Calcd for C15H14O6: C, 62.07;
H, 4.86. Found: C, 61.90; H, 4.91.
General glycosylation procedure in Table 1 and Fig. 2
Methyl 6-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-a-D-erythro-
hexopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (12a)
A suspension of glycosyl donor (2,3-unsaturated glycosyl acatate
1 or 13 (0.05 mmol) or 2,3-dideoxy glycosyl acetate 2 or 14
(0.05 mmol)), methyl 2,3,4-tri-O-benzyl-a-D-glucopyranoside (10)
(0.045 mmol) and MS 5A (100 wt% to glycosyl donor) in dry
CH2C◦l2 (40 mL mg-1 to glycosyl donor) was stirred for 30 min
at 25 C, and then to the suspension was added an activator as
listed in Table 1 and Fig. 2. After the suspension was stirred at
the temperature for the period as listed in Table 1 or Fig. 2,
triethylamine was added to the reaction mixture to quench
the reaction. The resulting mixture was poured into saturated
NaHCO3 aq., and extracted with ethyl acetate. The combined
organic layers were washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. The yields of the glycosides
and their a : b ratios were determined by HPLC analysis (column,
Develosil ODS-HG-5TM , (4.6 ¥ 250 mm) ¥ 2; eluent, 11.1% (v/v)
H2O in MeOH; flow rate, 0.5 mL min-1, 40 ◦C; detection, UV
250 nm).
Colorless syrup; Rf 0.40 (2/1 hexane–EtOAc); [a]2D9 +81.5 (c 2.26,
CHCl3); 1H NMR (CDCl3, TMS) d 8.02-7.95 (2H, m, ArH), 7.93-
7.88 (2H, m, ArH), 7.58-7.48 (2H, m, ArH), 7.42-7.22 (19H, m,
ArH), 5.11-5.01 (1H, m, H-4¢), 5.00 & 4.80 (2H, ABq, J = 10.8 Hz,
ArCH2), 4.98 & 4.68 (2H, ABq, J = 10.8 Hz, ArCH2), 4.73 (1H,
br-dd, H-1¢), 4.78 & 4.68 (2H, ABq, J = 12.0 Hz, ArCH2), 4.63
(1H, d, J1,2 = 3.6 Hz, H-1), 4.46 (1H, dd, J6¢,6¢ = 9.9 Hz, J5¢,6¢
=
2.1 Hz, H-6¢), 4.26 (1H, dd, J6¢,6¢ = 9.9 Hz, J5¢,6¢ = 6.0 Hz, H-6¢),
4.22 (1H, ddd, J4¢,5¢ = 9.3 Hz, J5¢,6¢ = 6.0 Hz, J5¢,6¢ = 2.1 Hz, H-
5¢), 4.01 (1H, dd, J2,3 = J3,4 = 9.3 Hz, H-3), 3.96 (1H, dd, J6,6
11.1 Hz, J5,6 = 4.8 Hz, H-6), 3.81 (1H, ddd, J4,5 = 10.2 Hz, J5,6
4.8 Hz, J5,6 = 1.2 Hz, H-5), 3.68 (1H, dd, J6,6 = 11.1 Hz, J5,6
=
=
=
1.2 Hz, H-6), 3.53 (1H, dd, J4,5 = 10.2 Hz, J3,4 = 9.3 Hz, H-4),
3.48 (1H, dd, J2,3 = 9.3 Hz, J1,2 = 3.6 Hz, H-2), 3.40 (3H, s, OMe),
2.21-2.11 (1H, m, H-3¢), 2.05-1.80 (3H, m, H-2¢ ¥ 2, H-3¢). Anal.
Calcd for C48H50O11: C, 71.80; H, 6.28. Found: C, 71.68; H, 6.31.
Methyl 6-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-a-D-erythro-hex-2-
nopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (11a)
Methyl 6-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-b-D-erythro-
hexopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (12b)
Colorless syrup; Rf 0.73 (1/1 hexane–EtOAc); [a]3D0 +84.1 (c 1.57,
CHCl3); 1H NMR (CDCl3, TMS) d 8.02-7.95 (4H, m, ArH), 7.66-
7.52 (2H, m, ArH), 7.52-7.22 (19H, m, ArH), 6.02 (1H, ddd, J2¢,3¢
10.2 Hz, J1¢,3¢ = 0.9 Hz, J3¢,4¢ = 0.9 Hz, H-3¢), 5.91 (1H, ddd, J2¢,3¢
10.2 Hz, J1¢,2¢ = 2.4 Hz, J2¢,4¢ = 2.1 Hz, H-2¢), 5.68 (1H, ddd, J4¢,5¢
7.2 Hz, J2¢,4¢ = 2.1 Hz, J3¢,4¢ = 0.9 Hz, H-4¢), 5.16 (1H, dd, J1¢,2¢
Colorless syrup; Rf 0.38 (2/1 hexane–EtOAc); [a]3D0 +32.6 (c 1.69,
CHCl3); 1H NMR (CDCl3, TMS) d 8.02-7.95 (4H, m, ArH), 7.61-
7.47 (2H, m, ArH), 7.44-7.22 (19H, m, ArH), 5.02 (1H, ddd, J3¢,4¢
=
=
=
=
=
9.3 Hz, J4¢,5¢ = 9.0 Hz, J3¢,4¢ = 5.1 Hz, H-4¢), 4.98 & 4.80 (2H, ABq,
J = 10.5 Hz, ArCH2), 4.88 & 4.59 (2H, ABq, J = 11.1 Hz, ArCH2),
2.4 Hz, J1¢,3¢ = 0.9 Hz, H-1¢), 4.99 & 4.80 (2H, ABq, J = 10.8 Hz,
ArCH2), 4.91 & 4.64 (2H, ABq, J = 11.4 Hz, ArCH2), 4.78 & 4.67
(2H, ABq, J = 12.0 Hz, ArCH2), 4.61 (1H, d, J1,2 = 3.6 Hz, H-1),
4.46 (1H, dd, J6¢,6¢ = 8.7 Hz, J5¢,6¢ = 4.5 Hz, H-6¢), 4.37 (1H, ddd,
J4¢,5¢ = 7.2 Hz, J5¢,6¢ = 5.1 Hz, J5¢,6¢ = 4.5 Hz, H-5¢), 4.34 (1H, dd,
J6¢,6¢ = 8.7 Hz, J5¢,6¢ = 5.1 Hz, H-6¢), 4.01 (1H, dd, J6,6 = 11.4 Hz,
J5,6 = 4.8 Hz, H-6), 4.00 (1H, dd, J2,3 = J3,4 = 9.3 Hz, H-3), 3.82-
3.72 (2H, m, H-5 & H-6), 3.53 (1H, dd, J3,4 = J4,5 = 9.3 Hz, H-4),
3.49 (1H, dd, J2,3 = 9.3 Hz, J1,2 = 3.6 Hz, H-2), 3.38 (3H, s, OMe);
Anal. Calcd for C48H48O11: C, 71.98; H, 6.04. Found: C, 71.83; H,
5.90.
4.78 & 4.65 (2H, ABq, J = 12.3 Hz, ArCH2), 4.60 (1H, d, J1,2 =
3.6 Hz, H-1), 4.56 (1H, dd, J6¢,6¢ = 12.0 Hz, J5¢,6¢ = 3.9 Hz, H-6¢),
4.43 (1H, br-dd, J1¢,2¢ = 9.0 Hz, H-1¢), 4.40 (1H, dd, J6¢,6¢ = 12.0 Hz,
J5¢,6¢ = 6.0 Hz, H-6¢), 4.09 (1H, br-dd, J6,6 = 10.5 Hz, H-6), 3.98
(1H, dd, J2,3 = J3,4 = 9.6 Hz, H-3), 3.93 (1H, ddd, J4¢,5¢ = 9.0 Hz,
J5¢,6¢ = 6.0 Hz, J5¢,6¢ = 3.9 Hz, H-5¢), 3.75 (1H, br-ddd, J4,5 = 9.6 Hz,
J5,6 = 3.9 Hz, H-5), 3.64 (1H, dd, J6,6 = 10.5 Hz, J5,6 = 3.9 Hz,
H-6), 3.56 (1H, dd, J3,4 = J4,5 = 9.6 Hz, H-4), 3.54 (1H, dd, J2,3
=
9.6 Hz, J1,2 = 3.6 Hz, H-2), 3.33 (3H, s, OMe), 2.40-2.30 (1H, m),
1.92-1.57 (3H, m). Anal. Calcd for C48H50O11: C, 71.80; H, 6.28.
Found: C, 71.70; H, 6.03.
3172 | Org. Biomol. Chem., 2010, 8, 3164–3178
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Methyl 6-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-a-D-threo-hex-2-
enopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (15a)
2.22-1.94 (3H, m, H-2¢ ¥ 2, H-3¢), 1.72-1.62 (1H, m, H-3¢). Anal.
Calcd for C48H50O11: C, 71.80; H, 6.28. Found: C, 71.50; H, 6.12.
Colorless viscous syrup; Rf 0.68 (1/1 hexane–EtOAc); [a]2D9 -80.9
(c 1.22, CHCl3); H NMR (CDCl3, TMS) d 8.07-8.01 (2H, m,
Methyl 6-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-b-D-threo-
hexopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (16b)
1
ArH), 7.99-7.92 (2H, m, ArH), 7.60-7.47 (2H, m, ArH), 7.47-7.17
(19H, m, ArH), 6.25 (1H, ddd, J2¢,3¢ = 10.2 Hz, J3¢,4¢ = 5.4 Hz,
J1¢,3¢ = 0.9 Hz, H-3¢), 6.09 (1H, dd, J2¢,3¢ = 10.2 Hz, J1¢,2¢ = 3.0 Hz,
H-2¢), 5.32 (1H, dd, J3¢,4¢ = 5.4 Hz, J4¢,5¢ = 1.8 Hz, H-4¢), 5.21 (1H,
dd, J1¢,2¢ = 3.0 Hz, J1¢,3¢ = 0.9 Hz, H-1¢), 4.97 & 4.80 (2H, ABq, J =
10.5 Hz, ArCH2), 4.87 & 4.58 (2H, ABq, J = 11.1 Hz, ArCH2),
4.76 & 4.65 (2H, ABq, J = 12.3 Hz, ArCH2), 4.62-4.40 (3H, m),
4.58 (1H, d, J1,2 = 3.6 Hz, H-1), 3.98 (1H, dd, J2,3 = J3,4 = 9.3 Hz,
H-3), 3.96 (1H, dd, J6,6 = 11.4 Hz, J5,6 = 4.8 Hz, H-6), 3.79 (1H,
dd, J6,6 = 11.4 Hz, J5,6 = 1.8 Hz, H-6), 3.76 (1H, ddd, J4,5 = 9.3 Hz,
J5,6 = 4.8 Hz, J5,6 = 1.8 Hz, H-5), 3.45 (1H, dd, J3,4 = J4,5 = 9.3 Hz,
H-4), 3.44 (1H, dd, J2,3 = 9.3 Hz, J1,2 = 3.6 Hz, H-2), 3.36 (3H, s,
OMe). Anal. Calcd for C48H48O11: C, 71.98; H, 6.04. Found: C,
71.80; H, 6.14.
Colorless syrup; Rf 0.78 (1/1 hexane–EtOAc); [a]3D1 -15.5 (c 0.10,
CHCl3); 1H NMR (CDCl3, TMS) d 8.11-8.05 (2H, m, ArH), 8.01-
7.96 (2H, m, ArH), 7.61-7.49 (2H, m, ArH), 7.47-7.22 (19H, m,
ArH), 5.20 (1H, br-ddd, H-4¢), 4.99 & 4.80 (2H, ABq, J = 11.1 Hz,
ArCH2), 4.88 & 4.58 (2H, ABq, J = 11.1 Hz, ArCH2), 4.80 & 4.66
(2H, ABq, J = 11.7 Hz, ArCH2), 4.63 (1H, d, J1,2 = 3.6 Hz, H-1),
4.52 (1H, dd, J6¢,6¢ = 11.1 Hz, J5¢,6¢ = 6.0 Hz, H-6¢), 4.39 (1H, br-dd,
J1¢,2¢ = 6.6 Hz, H-1¢), 4.37 (1H, dd, J6¢,6¢ = 11.1 Hz, J5¢,6¢ = 6.0 Hz,
H-6¢), 4.16 (1H, dd, J6,6 = 10.8 Hz, J5,6 = 1.5 Hz, H-6), 4.00 (1H,
br-ddd, J5¢,6¢ = 6.9 Hz, J5¢,6¢ = 6.0 Hz, H-5¢), 4.00 (1H, dd, J2,3
=
J3,4 = 9.6 Hz, H-3), 3.81 (1H, ddd, J4,5 = 9.6 Hz, J5,6 = 4.5 Hz,
J5,6 = 1.5 Hz, H-5), 3.66 (1H, dd, J6,6 = 10.8 Hz, J5,6 = 4.5 Hz,
H-6), 3.55 (1H, dd, J2,3 = 9.6 Hz, J1,2 = 3.6 Hz, H-2), 3.55 (1H,
dd, J3,4 = J4,5 = 9.6 Hz, H-4), 3.37 (3H, s, OMe), 2.25-2.15 (1H,
m, H-3¢), 2.03-1.71 (2H, m), 1.67-1.55 (1H, m). Anal. Calcd for
C48H50O11: C, 71.80; H, 6.28. Found: C, 71.61; H, 6.34.
Methyl 6-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-b-D-threo-hex-2-
enopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (15b)
White needles; m.p. 88.2-89.6 ◦C; Rf 0.83 (1/1 hexane–EtOAc);
[a]3D0 -85.6 (c 0.27, CHCl3); 1H NMR (CDCl3, TMS) d 8.04-7.99
(2H, m, ArH), 7.98-7.93 (2H, m, ArH), 7.60-7.49 (2H, m, ArH),
General glycosylation procedure in Table 3
A suspension of glycosyl donor (2,3-dideoxy glycosyl acatate
18 (0.05 mmol) or 2,3-unsaturated-4-keto glycosyl acetate 3
(0.05 mmol)), methyl 2,3,4-tri-O-benzyl-a-D-glucopyranoside (10)
(0.05 mmol) and MS 5A (100 wt% to glycosyl donor) in dry
CH2Cl2 (40 mL mg-1 to glycosyl donor) was stirred for 30 min at
25 ◦C, and then to the suspension was added an activator as listed
in Table 3. After the suspension was stirred at the temperature
for the period as listed in Table 3, pyridine was added to the
reaction mixture to quench the reaction. The resulting mixture was
poured into water, and extracted with ethyl acetate. The combined
organic layers were washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. Purification of the residue
by flash silica-gel column chromatography (hexane/ether = 1/1
(for the glycosylation using 18) or hexane–EtOAc = 1/1 (for the
glycosylation using 3) afforded disaccharide 19 and recovered 18
or disaccharide 17 and recovered 3 as indicated in Table 3. The
a : b ratios were determined by 1H NMR analysis.
7.45-7.22 (19H, m, ArH), 6.24 (1H, ddd, J2¢,3¢ = 10.2 Hz, J3¢,4¢
=
4.5 Hz, J1¢,3¢ = 1.2 Hz, H-3¢), 5.99 (1H, d, J2¢,3¢ = 10.2 Hz, H-2¢),
5.45 (1H, dd, J3¢,4¢ = 4.5 Hz, J4¢,5¢ = 3.0 Hz, H-4¢), 5.20 (1H, d,
J1¢,2¢ = 1.2 Hz, H-1¢), 4.98 & 4.82 (2H, ABq, J = 10.5 Hz, ArCH2),
4.88 & 4.69 (2H, ABq, J = 11.1 Hz, ArCH2), 4.80 & 4.66 (2H,
ABq, J = 12.0 Hz, ArCH2), 4.59 (1H, d, J1,2 = 3.6 Hz, H-1), 4.58
(1H, dd, J6¢,6¢ = 11.4 Hz, J5¢,6¢ = 7.2 Hz, H-6¢), 4.47 (1H, dd, J6¢,6¢
11.4 Hz, J5¢,6¢ = 5.4 Hz, H-6¢), 4.18 (1H, ddd, J5¢,6¢ = 7.2 Hz, J5¢,6¢
5.4 Hz, J4¢,5¢ = 3.0 Hz, H-5¢), 4.00 (1H, dd, J6,6 = 10.5 Hz, J5,6
=
=
=
2.1 Hz, H-6), 3.99 (1H, dd, J2,3 = 9.6 Hz, J3,4 = 9.3 Hz, H-3), 3.89
(1H, dd, J6,6 = 10.5 Hz, J5,6 = 3.6 Hz, H-6), 3.79 (1H, ddd, J4,5
9.6 Hz, J5,6 = 3.6 Hz, J5,6 = 2.1 Hz, H-5), 3.61 (1H, dd, J4,5
9.6 Hz, J3,4 = 9.3 Hz, H-4), 3.55 (1H, dd, J2,3 = 9.6 Hz, J1,2
=
=
=
3.6 Hz, H-2), 3.33 (3H, s, OMe). Anal. Calcd for C48H48O11: C,
71.98; H, 6.04. Found: C, 71.90; H, 6.09.
Methyl 6-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-a-D-threo-
hexopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (16a)
Methyl 6-O-(6¢-O-benzoyl-4¢-O-benzyl-2¢,3¢-dideoxy-a-D-erythro-
hexopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (19a)
Colorless syrup; Rf 0.80 (1/1 hexane–EtOAc); [a]3D0 +34.8 (c 0.91,
CHCl3); 1H NMR (CDCl3, TMS) d 8.11-8.06 (2H, m, ArH), 7.98-
7.93 (2H, m, ArH), 7.61-7.49 (2H, m, ArH), 7.48-7.41 (2H, m,
ArH), 7.40-7.20 (17H, m, ArH), 5.22 (1H, br-dd, H-1¢), 5.02 (1H,
br-ddd, H-4¢), 4.98 & 4.80 (2H, ABq, J = 10.8 Hz, ArCH2), 4.92
& 4.58 (2H, ABq, J = 11.4 Hz, ArCH2), 4.76 & 4.65 (2H, ABq,
J = 12.0 Hz, ArCH2), 4.61 (1H, d, J1,2 = 3.6 Hz, H-1), 4.40 (1H,
Colorless syrup; Rf 0.38 (9/1 toluene–EtOAc); [a]3D2 +65.3 (c 3.63,
CHCl3); 1H NMR (CDCl3, TMS) d 7.95 (2H, dd, Jo,m = 8.5 Hz,
Jo,p = 1.2 Hz, Ho of Bz), 7.52 (1H, tt, Jm,p = 7.4 Hz, Jo,p = 1.2 Hz,
Hp of Bz), 7.39-7.19 (23H, m, ArH), 4.99 & 4.81 (2H, ABq, J =
12.0 Hz, ArCH2), 4.95 & 4.62 (2H, ABq, J = 11.4 Hz, ArCH2),
4.85 (1H, br-s, H-1¢), 4.77 & 4.67 (2H, ABq, J = 12.0 Hz, ArCH2),
4.63 & 4.43 (2H, ABq, J = 11.7 Hz, ArCH2), 4.61 (1H, d, J1,2
3.5 Hz, H-1¢), 4.48-4.37 (2H, m, H-6¢ ¥ 2), 4.01 (1H, dd, J2,3 = J3,4
=
=
dd, J6¢,6¢ = 12.9 Hz, J5¢,6¢ = 9.9 Hz, H-6¢), 4.30 (1H, br-ddd, J5¢,6¢
9.9 Hz, J5¢,6¢ = 4.2 Hz, H-5¢), 4.28 (1H, dd, J6¢,6¢ = 12.9 Hz, J5¢,6¢
=
=
9.0 Hz, H-3), 3.99-3.94 (1H, m, H-5¢), 3.89 (1H, dd, J6,6 = 11.0 Hz,
J5,6 = 5.0 Hz, H-6), 3.77 (1H, ddd, J4,5 = 9.0 Hz, J5,6 = 5.0 Hz,
J5,6 = 1.5 Hz, H-5), 3.62 (1H, dd, J6,6 = 11.0 Hz, J5,6 = 1.5 Hz,
4.2 Hz, H-6¢), 3.99 (1H, dd, J2,3 = J3,4 = 9.3 Hz, H-3), 3.89 (1H,
dd, J6,6 = 11.1 Hz, J5,6 = 5.1 Hz, H-6), 3.78 (1H, ddd, J4,5 = 9.3 Hz,
J5,6 = 5.1 Hz, J5,6 = 1.5 Hz, H-5), 3.71 (1H, dd, J6,6 = 11.1 Hz,
J5,6 = 1.5 Hz, H-6), 3.43 (1H, dd, J2,3 = 9.3 Hz, J1,2 = 3.6 Hz,
H-2), 3.42 (1H, dd, J3,4 = J4,5 = 9.3 Hz, H-4), 3.38 (3H, s, OMe),
H-6), 3.52 (1H, dd, J3,4 = J4,5 = 9.0 Hz, H-4), 3.51 (1H, dd, J2,3
=
9.0 Hz, J1,2 = 3.5 Hz, H-2), 3.46 (1H, ddd, J3¢,4¢ = J4¢,5¢ = 10.2 Hz,
J3¢,4¢ = 4.5 Hz, H-4¢), 3.37 (3H, s, OMe), 2.11-2.06 (1H, m, H-3¢),
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 3164–3178 | 3173
©

View Article Online
1.93-1.67 (3H, m, H-2¢ ¥ 2 & H-3); Anal. Calcd for C48H52O10: C,
73.08; H, 6.64. Found: C, 72.78; H, 6.69; HRMS (ESI-TOF) m/z
811.3450 (811.3458 calcd for C48H52O10Na, [M+Na]+).
5.61 (1H, m, H-4¢), 5.26 (1H, d, J1¢,2¢ = 1.7 Hz, H-1¢), 4.62 (1H, dd,
J6,6 = 11.9 Hz, J5,6 = 4.1 Hz, H-6), 4.57-4.51 (2H, m, H-6¢ ¥ 2), 4.44
(1H, dd, J6,6 = 11.9 Hz, J5,6 = 2.4 Hz, H-6), 4.30 (1H, ddd, J5¢,6¢
=
5.9 Hz, J4¢,5¢ = J5¢,6¢ = 5.6 Hz, H-5¢), 3.99 (1H, ddd, J4,5 = 9.0 Hz,
J5,6 = 4.1 Hz, J5,6 = 2.4 Hz, H-5), 3.79 (1H, ddd, J3,4 = 9.9 Hz,
J4,5 = 9.0 Hz, J3,4 = 4.1 Hz, H-4), 2.30 (1H, m, H-3), 2.09 (3H, s,
OAc), 1.99 (1H, m, H-3), 1.86 (2H, m, H-2 ¥ 2); HRMS (ESI-TOF)
m/z 653.1977 (653.1999 calcd for C35H34O11Na, [M+Na]+).
Methyl 6-O-(6¢-O-benzoyl-4¢-O-benzyl-2¢,3¢-dideoxy-a-D-erythro-
hexopyranosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (19b)
Colorless syrup; Rf 0.27 (9/1 toluene–EtOAc); [a]3D2 +30.1 (c 2.86,
CHCl3); 1H NMR (CDCl3, TMS) d 7.99 (2H, dd, Jo,m = 8.3 Hz,
Jo,p = 1.2 Hz, Ho of Bz), 7.53 (1H, tt, Jm,p = 7.3 Hz, Jo,p = 1.2 Hz,
Hp of Bz), 7.41-7.21 (23H, m, ArH), 4.97 & 4.79 (2H, ABq, J =
11.0 Hz, ArCH2), 4.85 & 4.55 (2H, ABq, J = 11.2 Hz, ArCH2),
4.78 & 4.64 (2H, ABq, J = 11.9 Hz, ArCH2), 4.60 & 4.43 (2H,
ABq, J = 11.5 Hz, ArCH2), 4.59 (1H, d, J1,2 = 3.7 Hz, H-1),
4.59-4.53 (1H, m, H-6¢), 4.47 (1H, J6¢,6¢ = 11.7 Hz, J5¢,6¢ = 5.6 Hz,
H-6¢), 4.35 (1H, dd, J1¢,2¢ = 9.3 Hz, J1¢,2¢ = 2.1 Hz, H-1¢), 4.05 (1H,
Methyl
6-O-(6¢-O-benzoyl-4¢-O-(4¢¢,6¢¢-di-O-benzoyl-2¢¢,3¢¢-
dideoxy-a-D-erythro-hex-2- enopyranosyl)-D-erythro-hexopyra-
nosyl)-2,3,4-tri-O-benzyl-a-D-glucopyranoside (22)
A suspension of disaccharide 21a (33.4 mg, 0.0530 mmol),
methyl 2,3,4-tri-O-benzyl-a-D-glucopyranoside (10) (12.3 mg,
0.0265 mmol) and MS 5A (33.4 mg, 100 wt% to glycosyl donor)
in dry toluene (1.34 mL, 40 mL mg-1 to glycosyl donor) was
stirred for 30 min at 25 ◦C, and then to t◦he suspension was added
TMSOTf (3.0 mL, 0.015 mmol) at -40 C. After the suspension
was stirred at -40 ◦C for 30 min, pyridine was added to the
reaction mixture to quench the reaction. The resulting mixture
was poured into water, and extracted with EtOAc. The combined
organic layers were washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. Purification of the residue by
flash silica-gel column chromatography (hexane–EtOAc = 1/1)
afforded trisaccharide 22 (21.4 mg, 78%, a : b = 85 : 15). 22a:
Colorless syrup; Rf 0.56 (1/1 hexane–EtOAc); [a]3D2 +114.7 (c 0.55,
CHCl3); 1H NMR (CDCl3, TMS) d 8.02-7.98 (6H, m, ArH), 7.57-
7.22 (24H, m, ArH), 6.04 (1H, br-d, J = 10.2 Hz, H-3¢¢), 5.81
(1H, ddd, J2¢¢,3¢¢ = 10.2 Hz, J1¢¢,2¢¢ = J2¢¢,4¢¢ = 2.7 Hz, H-2¢¢), 5.68 (1H,
ddd, J4¢¢,5¢¢ = 10.2 Hz, J2¢¢,4¢¢ = 2.7 Hz, J3¢¢,4¢¢ = 1.2 Hz, H-4¢¢), 5.29
(1H, br-s, H-1¢¢), 4.99 & 4.80 (2H, ABq, J = 10.7 Hz, ArCH2), 4.96
dd, J6¢,6¢ = 11.7 Hz, J5¢,6¢ = 2.0 Hz, H-6¢), 4.00 (1H, dd, J2,3
=
J3,4 = 9.2 Hz, H-3), 3.73 (1H, m, H-5), 3.68-3.57 (2H, m, H-6 &
H-5¢), 3.61 (1H, dd, J6,6 = 10.5 Hz, J5,6 = 10.0 Hz, H-6), 3.54 (1H,
dd, J3,4 = J4,5 = 9.0 Hz, H-4), 3.52 (1H, dd, J2,3 = 9.2 Hz, J1,2
=
3.7 Hz, H-2), 3.41 (1H, ddd, J3¢,4¢ = J4¢,5¢ = 9.2 Hz, J3¢,4¢ = 5.3 Hz,
H-4¢), 3.31 (3H, s, OMe), 2.29-2.24 (1H, m, H-3¢), 1.83-1.42 (3H,
m, H-2¢ ¥ 2 & H-3); HRMS (ESI-TOF) m/z 811.3448 (811.3458
calcd for C48H52O10Na, [M+Na]+).
6-O-Benzoyl-4-O-(4¢,6¢-di-O-benzoyl-2¢,3¢-dideoxy-D-erythro-hex-
2-enopyranosyl)-2,3- dideoxy-a-D-erythro-hexopyranosyl Acetate
(21)
A suspension of 2,3-unsaturated glycosyl acatate 1 (13.4 mg,
0.0338 mmol), 2,3-dideoxy glycosyl acetate 20 (19.8 mg,
0.0677 mmol) and MS 5A (13.4 mg, 100 wt% to glycosyl donor)
in dry CH2Cl2 (0.536 mL, 40 mL mg-1 to glycosyl donor) was
stirred for 30 min at 25 ◦ C, and then to the suspension was
added TMSOTf (3.7 mL, 0.020 mmol) at -80 ◦C. After the
suspension was stirred at -80 ◦C for 30 min, pyridine was added
to the reaction mixture to quench the reaction. The resulting
mixture was poured into water, and extracted with EtOAc. The
combined organic layers were washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. Purification of the
residue by preparative TLC (chloroform–EtOAc = 9/1) afforded
disaccharide 21 (17.8 mg, 81%, a : b = 76 : 24). 21a: Colorless
syrup; Rf 0.61 (1/1 hexane–EtOAc); [a]3D2 +115.6 (c 5.01, CHCl3);
1H NMR (CDCl3, TMS) d 8.06-7.97 (6H, m, ArH), 7.57-7.48 (3H,
m, ArH), 7.44-7.34 (6H, m, ArH), 6.13 (1H, m, H-1), 6.06 (1H,
dd, br-d, J2¢,3¢ = 10.6 Hz, H-3¢), 5.84 (1H, ddd, J2¢,3¢ = 10.6 Hz,
J1¢,2¢ = 2.4 Hz, J2¢,4¢ = 2.2 Hz, H-2¢), 5.68 (1H, br-dd, J = 9.2 Hz,
J = 2.2 Hz, H-4¢), 5.33 (1H, m, H-1¢), 4.67 (1H, dd, J6,6 = 11.7 Hz,
J5,6 = 2.4 Hz, H-6), 4.52 (1H, dd, J6,6 = 11.7 Hz, J5,6 = 5.1 Hz, H-6),
4.38-4.28 (3H, m, H-5¢ & H-6¢ ¥ 2), 4.08 (1H, ddd, J4,5 = 9.7 Hz,
& 4.60 (2H, ABq, J = 11.0 Hz, ArCH2), 4.86 (1H, br-d, J1¢,2¢
=
2.4 Hz, H-1¢), 4.77 & 4.67 (2H, ABq, J = 12.2 Hz, ArCH2), 4.62
(1H, br-d, H-1), 4.55 (1H, dd, J6¢,6¢ = 11.7 Hz, J5¢,6¢ = 2.1 Hz, H-
6¢), 4.44-4.37 (3H, m, H-6¢ & H-6¢¢ ¥ 2), 4.34 -4.26 (1H, m, H-5¢¢),
4.04-3.96 (2H, m, H-3 & H-5¢), 3.93-3.82 (2H, m, H-6 & H-4¢),
3.79-3.75 (1H, m, H-5), 3.64 (1H, dd, J6,6 = 11.4 Hz, J5,6 = 1.2 Hz,
H-6), 3.51 (1H, dd, J3,4 = J4,5 = 9.3 Hz, H-4), 3.48 (1H, dd, J2,3
=
9.3 Hz, J1,2 = 3.6 Hz, H-2), 3.38 (3H, s, OMe), 2.12-2.07 (1H,
m, H-3¢), 1.92-1.59 (3H, m, H-2¢ ¥ 2 & H-3¢); 13C NMR (CDCl3)
d 166.42, 166.14, 165.80, 138.74, 138.31, 138.21, 133.39, 132.95,
130.18, 129.85, 129.80, 129.62, 129.46, 128.39, 128.14, 127.96,
127.91, 127.65, 97.89, 96.31, 89.96, 82.23, 80.16, 78.02, 75.78,
75.01, 73.25, 69.99, 69.83, 67.39, 66.08, 65.54, 64.43, 63.59, 55.09,
28.59, 23.08; HRMS (ESI-TOF) m/z 1057.3982 (1057.3986 calcd
for C61H62O15Na, [M+Na]+). 22b: Colorless syrup; Rf 0.56 (1/1
1
hexane–EtOAc); [a]D31 +70.4 (c 0.50, CHCl3); H NMR (CDCl3,
TMS) d 8.04-7.97 (6H, m, ArH), 7.59-7.23 (24H, m, ArH), 6.05
(1H, d, J2¢¢,3¢¢ = 10.2 Hz, H-3¢¢), 5.82 (1H, ddd, J2¢¢,3¢¢ = 10.2 Hz,
J1¢¢,2¢¢ = J2¢¢,4¢¢ = 2.7 Hz, H-2¢¢), 5.67 (1H, m, H-4¢¢), 5.25 (1H, br-s,
H-1¢¢), 4.98 & 4.79 (2H, ABq, J = 10.7 Hz, ArCH2), 4.86 & 4.56
(2H, ABq, J = 11.0 Hz, ArCH2), 4.78 & 4.65 (2H, ABq, J =
12.0 Hz, ArCH2), 4.67 (1H, dd, J6¢,6¢ = 12.0 Hz, J5¢,6¢ = 3.4 Hz,
H-6¢), 4.60 (1H, d, J1,2 = 3.3 Hz, H-1), 4.47 (1H, m, H-6¢), 4.38
(1H, br-dd, J1¢,2¢ = 9.3 Hz, H-1¢), 4.39-4.32 (3H, m, H-5¢¢ & H-6¢¢ ¥
2), 4.06 (1H, dd, J6,6 = 11.0 Hz, J5,6 = 1.2 Hz, H-6), 3.97 (1H,
dd, J2,3 = J3,4 = 9.6 Hz, H-3), 3.91-3.81 (1H, m, H-4¢), 3.79-3.54
J5,6 = 5.1 Hz, J5,6 = 2.4 Hz, H-5), 3.98 (1H, ddd, J3,4 = J4,5
=
9.9 Hz, J3,4 = 4.6 Hz, H-4), 2.22 (1H, m, H-3), 2.11 (3H, s, OAc),
1.95 (1H, m, H-3), 1.80 (2H, m, H-2 ¥ 2); Anal Calcd for C35H34O11:
C, 66.66; H, 5.43. Found: C, 66.60; H, 5.52.; HRMS (ESI-TOF)
m/z 653.1996 (653.1999 calcd for C35H34O11Na, [M+Na]+). 21b:
Colorless syrup; Rf 0.58 (1/1 hexane–EtOAc); [a]3D3 +150.5 (c 0.73,
CHCl3); 1H NMR (CDCl3, TMS) d 8.07-7.99 (6H, m, ArH), 7.60-
7.53 (3H, m, ArH), 7.48-7.38 (6H, m, ArH), 6.13-6.08 (2H, m, H-1
& H-3¢), 5.99 (1H, ddd, J2¢,3¢ = 10.2 Hz, J1¢,2¢ = J2¢,4¢ = 1.7 Hz, H-2¢),
(4H, m, H-4, H-5, H-6 & H-5¢), 3.53 (1H, dd, J2,3 = 9.6 Hz, J1,2
=
3.3 Hz, H-2), 3.33 (3H, s, OMe), 2.33-3.23 (1H, m, H-3¢), 1.88-
1.78 & 1.70-1.42 (3H, m, H-2¢ ¥ 2 & H-3¢); 13C NMR (CDCl3)
3174 | Org. Biomol. Chem., 2010, 8, 3164–3178
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
d 166.39, 166.16, 166.78, 165.78, 138.84, 138.44, 138.19, 133.37,
132.96, 129.85, 129.71, 129.67, 128.42, 128.37, 128.32, 128.14,
128.01, 127.91, 127.81, 127.77, 127.60, 101.89, 98.02, 90.82, 82.22,
79.91, 77.63, 76.01, 75.75, 74.86, 73.33, 70.16, 69.76, 67.54, 67.44,
66.01, 64.71, 63.63, 55.11, 29.30, 26.17; HRMS (ESI-TOF) m/z
1057.3977 (1057.3986 calcd for C61H62O15Na, [M+Na]+).
0.0217 mmol) and MS 5A (22.7 mg, 100 wt% to glycosyl donor)
in dry toluene (0.908 mL, 40 mL mg-1 to glycosyl donor) was
stirred for 30 min at 25 ◦C, and then to the suspension was
added TMSOTf (2.5 mL 0.013 mmol) at -40 ◦C. After the
suspension was stirred at -40 ◦C for 30 min, pyridine was added
to the reaction mixture to quench the reaction. The resulting
mixture was poured into water, and extracted with EtOAc.
The combined organic layers were washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. Purification of
the residue by flash silica-gel column chromatography (hexane–
EtOAc = 1/1) afforded trisaccharide 25 (22.2 mg, 75%, a : b =
79 : 21). 25a: Colorless syrup; Rf 0.70 (1/1 hexane–EtOAc); [a]D32
+28.3 (c 1.42, CHCl3); 1H NMR (CDCl3, TMS) d 8.08-8.00 (4H,
m, ArH), 7.59-7.23 (21H, m, ArH), 6.85 (1H, dd, J2¢,3¢ = 10.2 Hz,
J1¢,2¢ = 3.7 Hz, H-2¢), 6.11 (1H, d, J2¢,3¢ = 10.2 Hz, H-3¢), 5.98
(1H, br-d, J2¢¢,3¢¢ = 10.0 Hz, J3¢¢,4¢¢ = 2.7 Hz, H-3¢¢), 5.83 (1H,
ddd, J2¢¢,3¢¢ = 10.0 Hz, J1¢¢,2¢¢ = 2.7 Hz, J2¢¢,4¢¢ = 2.2 Hz, H-2¢¢),
5.68 (1H, ddd, J4¢¢,5¢¢ = 8.9 Hz, J3¢¢,4¢¢ = 2.7 Hz, J2¢¢,4¢¢ = 2.2 Hz,
6-O-(4¢,6¢-Di-O-benzoyl-2¢,3¢-dideoxy-D-erythro-hex-2-
enopyranosyl)-2,3-dideoxy-a-D-glycelo-hex-2-enopyranos-4-ulosyl
Acetate (24)
A suspension of 2,3-unsaturated glycosyl acatate 1 (23.2 mg,
0.0585 mmol), 2,3-unsaturated-4-keto glycosyl acetate 23
(22.0 mg, 0.118 mmol) and MS 5A (23.2 mg, 100 wt% to glycosyl
donor) in dry CH2Cl2 (0.928 mL, 40 mL mg-1 to glycosyl donor)
was stirred for 30 min at 25 ◦C, and then to the suspension
was added TMSOTf (3.2 mL 0.017 mmol) at -75 ◦C. After the
suspension was stirred at -75 ◦C for 30 min, pyridine was added
to the reaction mixture to quench the reaction. The resulting
mixture was poured into water, and extracted with EtOAc. The
combined organic layers were washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. Purification of the
residue by preparative TLC (chloroform–EtOAc = 9/1) afforded
disaccharide 24 (27.9 mg, 91%, a : b = 79 : 21). 24a: Colorless
syrup; Rf 0.59 (9/1 chloroform–EtOAc); [a]3D2 +12.1 (c 2.68,
CHCl3); 1H NMR (CDCl3, TMS) d 8.09-7.99 (4H, m, ArH),
7.60-7.49 (2H, m, ArH), 7.46-7.36 (4H, m, ArH), 6.91 (1H, dd,
J2,3 = 10.2 Hz, J1,2 = 3.7 Hz, H-2), 6.56 (1H, d, J1,2 = 3.7 Hz,
H-1), 6.27 (1H, d, J2,3 = 10.2 Hz, H-3), 6.05 (1H, br-d, J =
10.5 Hz, H-3¢), 5.90 (1H, ddd, J2¢,3¢ = 10.2 Hz, J2¢,4¢ = 2.0 Hz,
J1¢,2¢ = 2.7 Hz, H-2¢), 5.70 (1H, ddd, J4¢,5¢ = 9.5 Hz, J3¢,4¢ = 3.2 Hz,
H-4¢¢), 5.34 (1H, d, J1¢,2¢ = 3.7 Hz, H-1¢), 5.07 (1H, d, J1¢¢,2¢¢
=
2.7 Hz, H-1¢¢), 5.00 & 4.80 (2H, ABq, J = 10.7 Hz, ArCH2), 4.91
& 4.57 (2H, ABq, J = 11.0 Hz, ArCH2), 4.79 & 4.66 (2H, ABq,
J = 12.2 Hz, ArCH2), 4.64 (1H, dd, J6¢¢,6¢¢ = 11.9 Hz, J5¢¢,6¢¢
=
2.4 Hz, H-6¢¢), 4.59 (1H, d, J1,2 = 3.7 Hz, H-1), 4.51 (1H, m, H-
5¢), 4.47 (1H, dd, J6¢¢,6¢¢ = 11.9 Hz, J5¢¢,6¢¢ = 5.6 Hz, H-6¢¢), 4.36
(1H, m, H-5¢¢), 4.30 (1H, dd, J6¢,6¢ = 11.0 Hz, J5¢,6¢ = 3.9 Hz, H-6¢),
4.03 (1H, dd, J6,6 = 11.2 Hz, J5,6 = 4.4 Hz, H-6), 4.00 (1H, dd,
J2,3 = J3,4 = 9.3 Hz, H-3), 3.82 (1H, m, H-6), 3.79 (1H, m, H-5),
3.71 (1H, dd, J6¢,6¢ = 11.0 Hz, J5¢,6¢ = 2.4 Hz, H-6¢), 3.53 (1H,
dd, J3,4 = 9.5 Hz, J4,5 = 6.8 Hz, H-4), 3.51 (1H, dd, J2,3
=
9.3 Hz, J1,2 = 3.7 Hz, H-2), 3.35 (3H, s, OMe); 13C NMR
(CDCl3) d 193.69, 166.34, 165.78, 143.51, 138.62, 138.19, 138.08,
133.32, 132.88, 129.98, 129.75, 129.51, 128.45, 128.42, 128.39,
128.26, 128.03, 127.93, 127.83, 127.73, 127.63, 127.55, 127.47,
98.07, 94.09, 93.56, 81.98, 79.99, 77.67, 75.72, 74.88, 74.09,
73.33, 69.98, 67.61, 67.13, 66.13, 66.06, 63.66, 55.22; HRMS (ESI-
TOF) m/z 949.3407 (949.3411 calcd for C54H54O14Na, [M+Na]+).
25b: Colorless syrup; Rf 0.67 (1/1 hexane–EtOAc); [a]3D2 +110.6 (c
0.64, CHCl3); 1H NMR (CDCl3, TMS) d 8.06-7.98 (4H, m, ArH),
J2¢,4¢ = 2.0 Hz, H-4¢), 5.13 (1H, br-s, H-1¢), 4.68 (1H, dd, J5,6
4.2 Hz, J5,6 = 2.7 Hz, H-5), 4.65 (1H, dd, J6¢,6¢ = 10.5 Hz, J5¢,6¢
=
=
2.7 Hz, H-6¢), 4.48 (1H, dd, J6¢,6¢ = 10.5 Hz, J5¢,6¢ = 5.4 Hz, H-6¢),
4.40 (1H, m, H-5¢), 4.38 (1H, dd, J6,6 = 11.0 Hz, J5,6 = 4.2 Hz,
H-6), 3.90 (1H, dd, J6,6 = 11.0 Hz, J5,6 = 2.7 Hz, H-6), 2.14
(3H, s, OAc); Anal. Calcd for C28H26O10: C, 64.36; H, 5.02. Found:
C, 64.59; H, 5.20; HRMS (ESI-TOF) m/z 545.1406 (545.1424
calcd for C28H26O10Na, [M+Na]+). 24b:Colorless syrup; Rf 0.52
7.59-7.22 (21H, m, ArH), 6.75 (1H, dd, J2¢,3¢ = 10.5 Hz, J1¢,2¢
=
1
(9/1 chloroform–EtOAc); [a]3D2 +57.5 (c 0.93, CHCl3); H NMR
1.7 Hz, H-2¢), 6.12 (1H, dd, J2¢,3¢ = 10.5 Hz, J1¢,3¢ = 1.4 Hz, H-3¢),
(CDCl3, TMS) d 8.06-8.01 (4H, m, ArH), 7.60-7.52 (2H, m, ArH),
7.45-7.40 (4H, m, ArH), 6.93 (1H, dd, J2,3 = 10.2 Hz, J1,2 = 3.7 Hz,
H-2), 6.57 (1H, d, J1,2 = 3.7 Hz, H-1), 6.21 (1H, d, J2,3 = 10.2 Hz,
5.99 (1H, br-d, J2¢¢,3¢¢ = 10.2 Hz, H-3¢¢), 5.85 (1H, ddd, J2¢¢,3¢¢ =
10.0 Hz, J1¢¢,2¢¢ = J2¢¢,4¢¢ = 2.2 Hz, H-2¢¢), 5.68 (1H, m, H-4¢¢), 5.17
(1H, br-d, J1¢,2¢ = 1.7 Hz, H-1¢), 5.10 (1H, m, H-1¢¢), 4.99 & 4.80
(2H, ABq, J = 10.7 Hz, ArCH2), 4.88 & 4.60 (2H, ABq, J =
11.2 Hz, ArCH2), 4.76 & 4.64 (2H, ABq, J = 11.4 Hz, ArCH2),
4.58-4.52 (1H, m, H-6¢¢), 4.57 (1H, d, J1,2 = 3.6 Hz, H-1), 4.48-
4.39 (2H, m, H-5¢¢ & H-6¢¢), 4.27 (1H, m, H-5¢), 4.21 (1H, dd,
J6¢,6¢ = 11.0 Hz, J5¢,6¢ = 4.9 Hz, H-6¢), 4.06 (1H, m, H-6), 3.99
H-3), 6.04 (1H, br-d, H-3¢), 5.91 (1H, ddd, J2¢,3¢ = 10.2 Hz, J2¢,4¢
2.2 Hz, J1¢,3¢ = 1.2 Hz, H-2¢), 5.70 (1H, ddd, J4¢,5¢ = 9.5 Hz, J3¢,4¢
=
=
3.8 Hz, J2¢,4¢ = 1.2 Hz, H-4¢), 5.26 (1H, m, H-1¢), 4.68 (1H, m,
H-5), 4.65 (1H, dd, J6¢,6¢ = 11.0 Hz, J5¢,6¢ = 2.7 Hz, H-6¢), 4.48 (1H,
dd, J6¢,6¢ = 11.0 Hz, J5¢,6¢ = 5.4 Hz, H-6¢), 4.40 (1H, m, H-5¢), 4.38
(1H, dd, J6,6 = 10.7 Hz, J5,6 = 4.1 Hz, H-6), 3.90 (1H, dd, J6,6
=
(1H, dd, J2,3 = 9.5 Hz, J3,4 = 9.0 Hz, H-3), 3.96 (1H, dd, J6¢,6¢ =
10.7 Hz, J5,6 = 2.7 Hz, H-6), 2.10 (3H, s, OAc); HRMS (ESI-TOF)
m/z 545.1425 (545.1424 calcd for C28H26O10Na, [M+Na]+).
11.0 Hz, J5¢,6¢ = 3.2 Hz, H-6¢), 3.78-3.71 (2H, m, H-5& H-6),
3.52 (1H, dd, J4,5 = 9.7 Hz, J3,4 = 9.0 Hz, H-4), 3.49 (1H, dd,
J2,3 = 9.5 Hz, J1,2 = 3.4 Hz, H-2), 3.31 (3H, s, OMe); 13C NMR
(CDCl3) d 193.63, 166.32, 165.80, 146.68, 138.72, 138.38, 138.11,
133.39, 132.95, 129.94, 129.79, 129.54, 129.38, 128.98, 128.49,
128.42, 128.32, 128.11, 128.01, 127.95, 127.90, 127.85, 127.81,
127.65, 98.07, 95.90, 94.59, 82.15, 79.90, 78.24, 75.77, 74.80,
73.32, 69.70, 67.54, 67.35, 67.25, 66.16, 63.76, 55.21; HRMS
(ESI-TOF) m/z 949.3402 (949.3411 calcd for C54H54O14Na,
[M+Na]+).
Methyl 6-O-(6¢-O-Benzoyl-6¢-O-(4¢¢,6¢¢-di-O-benzoyl-2¢¢,3¢¢-
dideoxy-a-D-erythro-hex-2- enopyranosyl)-2¢,3¢-dideoxy-D-glycelo-
hex-2-enopyranos-4-ulosyl)-2,3,4-tri-O-benzyl-a-D-
glucopyranoside (25)
A suspension of disaccharide 24a (22.7 mg, 0.0434 mmol),
methyl 2,3,4-tri-O-benzyl-a-D-glucopyranoside (10) (10.1 mg,
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 3164–3178 | 3175
©

View Article Online
6-O-(6¢-O-Benzoyl-4¢-O-benzyl-2¢,3¢-dideoxy- D -erythro-
hexopyranosyl)-2,3-dideoxy-a-D-glycelo-hex-2-enopyranos-4-
ulosyl acetate (26)
0.0222 mmol) and MS 5A (22.6 mg, 100 wt% to glycosyl donor)
in dry toluene (0.904 mL, 40 mL mg-1 to glycosyl donor) was
stirred for 30 min at 25 ◦C, and then to the suspension was added
TMSOTf (2.6 mL 0.013 mmol) at -35 ◦C. After the suspension
was stirred at -35 ◦C for 30 min, pyridine was added to the
reaction mixture to quench the reaction. The resulting mixture
was poured into water, and extracted with EtOAc. The combined
organic layers were washed with brine, dried over anhydrous
Na2SO4, and concentrated in vacuo. Purification of the residue by
flash silica-gel column chromatography (hexane–EtOAc = 1/1)
afforded trisaccharide 27 (16.4 mg, 81%, a : b = 78 : 22). 27a:
Colorless syrup; Rf 0.43 (3/5/3 hexane–chloroform/ether); [a]D31
A suspension of 2,3-dideoxy glycosyl acatate 18 (41.3 mg,
0.107 mmol), 2,3-unsaturated-4-keto glycosyl acetate 23 (10.0 mg,
0.0537 mmol) and MS 5A (41.3 mg, 100 wt% to glycosyl donor)
in dry CH2Cl2 (1.65 mL, 40 mL mg-1 to glycosyl donor) was
stirred for 30 min at 25 ◦C, and then to the suspension was added
TMSOTf (3.1 mL◦0.016 mmol) at -50 ◦C. After the suspension
was stirred at -50 C for 1 h, pyridine was added to the reaction
mixture to quench the reaction. The resulting mixture was poured
into water, and extracted with EtOAc. The combined organic
layers were washed with brine, dried over anhydrous Na2SO4, and
concentrated in vacuo. Purification of the residue by flash silica-
gel column chromatography (hexane–EtOAc = 1/1) afforded
disaccharide 26 (24.1 mg, 88%, a : b = 89 : 11). 26a: Colorless
1
+28.6 (c 5.05, CHCl3); H NMR (CDCl3, TMS) d 8.02 (2H, dd,
Jo,m = 8.3 Hz, Jo,p = 1.2 Hz, Ho of Bz), 7.52 (1H, tt, Jm,p = 6.6 Hz,
Jo,p = 1.2 Hz, Hp of Bz), 7.39 (2H, dd, Jo,m = 8.3 Hz, Jm,p = 6.6 Hz,
Hm of Bz), 7.36-7.16 (20H, m, ArH), 6.84 (1H, dd, J2¢,3¢ = 10.2 Hz,
J1¢,2¢ = 3.7 Hz, H-2¢), 6.09 (1H, d, J2¢,3¢ = 10.2 Hz, H-3¢), 5.34
(1H, d, J1¢,2¢ = 3.7 Hz, H-1¢), 4.98 & 4.80 (2H, ABq, J = 11.0 Hz,
ArCH2), 4.89 & 4.57 (2H, ABq, J = 11.2 Hz, ArCH2), 4.79 &
4.66 (2H, ABq, J = 12.2 Hz, ArCH2), 4.77 (1H, br-s, H-1¢¢),
4.63-4.49 (3H, m, H-5¢, H-6¢¢ ¥ 2), 4.61 & 4.43 (2H, ABq, J =
11.9 Hz, ArCH2), 4.59 (1H, br, H-1), 4.10 (1H, dd, J6¢,6¢ = 10.7 Hz,
J5¢,6¢ = 4.9 Hz, H-6¢), 4.05-4.00 (2H, m, H-6, H-5¢¢), 4.00 (1H, dd,
J2,3 = J3,4 = 9.8 Hz, H-3), 3.82-3.75 (2H, m, H-5, H-6), 3.67 (1H,
syrup; Rf 0.40 (3/5/3 hexane–chloroform/ether); [a]3D2 +2.7 (c
1
6.75, CHCl3); H NMR (CDCl3, TMS) d 8.03 (2H, dd, Jo,m
8.3 Hz, Jo,p = 1.2 Hz, Ho of Bz), 7.58 (1H, tt, Jm,p = 7.3 Hz, Jo,p
=
=
1.2 Hz, Hp of Bz), 7.41 (2H, dd, Jo,m = 8.3 Hz, Jm,p = 7.3 Hz, Hm of
Bz), 7.32-7.17 (5H, m, ArH), 6.96 (1H, dd, J2,3 = 10.2 Hz, J1,2
3.7 Hz, H-2), 6.57 (1H, d, J1,2 = 3.7 Hz, H-1), 6.26 (1H, d, J2,3
=
=
10.2 Hz, H-3), 4.82 (1H, br-s, H-1¢), 4.64 (1H, dd, J5,6 = 3.9 Hz,
J5,6 = 2.7 Hz, H-5), 4.63 & 4.46 (2H, ABq, J = 11.9 Hz, ArCH2),
4.61 (1H, dd, J6¢,6¢ = 11.7 Hz, J5¢,6¢ = 2.5 Hz, H-6¢), 4.55 (1H, dd,
J6¢,6¢ = 11.7 Hz, J5¢,6¢ = 4.9 Hz, H-6¢), 4.23 (1H, dd, J6,6 = 11.0 Hz,
J5,6 = 3.9 Hz, H-6), 4.00 (1H, ddd, J4¢,5¢ = 10.0 Hz, J5¢,6¢ = 4.9 Hz,
J5¢,6¢ = 2.5 Hz, H-5¢), 3.76 (1H, dd, J6,6 = 11.0 Hz, J5,6 = 2.7 Hz,
H-6), 3.47 (1H, ddd, J3¢,4¢ = J4¢,5¢ = 10.0 Hz, J3¢,4¢ = 4.4 Hz, H-
4¢), 2.13 (3H, s, OAc), 2.10-2.03 (1H, m, H-3¢), 1.91-1.85 (1H, m,
H-2¢), 1.77-1.68 (2H, m, H-2¢ & H-3¢); Anal. Calcd for C28H30O9:
C, 65.87; H, 5.92. Found: C, 65.88; H, 6.09; HRMS (ESI-TOF)
m/z 533.1783 (533.1788 calcd for C28H30O9Na, [M+Na]+). 26b:
dd, J6¢,6¢ = 10.7 Hz, J5¢,6¢ = 2.7 Hz, H-6¢), 3.52 (1H, dd, J3,4
=
J4,5 = 9.8 Hz, H-4), 3.51 (1H, dd, J2,3 = 9.8 Hz, J1,2 = 3.4 Hz,
H-2), 3.43 (1H, ddd, J3¢¢,4¢¢ = J4¢¢,5¢¢ = 9.5 Hz, J3¢¢,4¢¢ = 5.4 Hz, H-4¢¢),
3.34 (3H, s, OMe), 2.04-1.97 (1H, m, H-3¢¢), 1.84-1.62 (3H, m,
H-2¢¢ ¥ 2, H-3¢¢); 13C NMR (CDCl3) d 193.76, 166.40, 143.51,
138.60, 138.16, 138.05, 132.70, 130.31, 129.62, 128.41, 128.34,
128.31, 128.18, 127.98, 127.88, 127.76, 127.70, 127.65, 127.62,
127.57, 127.45, 97.97, 95.83, 93.40, 81.95, 79.88, 77.67, 75.67,
74.86, 73.92, 73.23, 72.61, 70.35, 70.17, 69.94, 67.44, 64.79, 64.28,
55.14, 28.69, 23.67; HRMS (ESI-TOF) m/z 937.3779 (937.3775
calcd for C54H54O14Na, [M+Na]+). 27b: Colorless syrup; Rf 0.38
(3/5/3 hexane–chloroform/ether); [a]3D1 +86.6 (c 0.56, CHCl3); 1H
NMR (CDCl3, TMS) d 8.00 (2H, dd, Jo,m = 8.3 Hz, Jo,p = 1.2 Hz,
Ho of Bz), 7.53 (1H, tt, Jm,p = 7.3 Hz, Jo,p = 1.2 Hz, Hp of Bz),
7.41 (2H, dd, Jo,m = 8.3 Hz, Jm,p = 7.3 Hz, Hm of Bz), 7.36-7.19
(20H, m, ArH), 6.73 (1H, dd, J2¢,3¢ = 10.5 Hz, J1¢,2¢ = 1.5 Hz, H-
2¢), 6.11 (1H, dd, J2¢,3¢ = 10.5 Hz, J1¢,3¢ = 1.5 Hz, H-3¢), 5.13 (1H,
br-s, H-1¢), 4.99 & 4.80 (2H, ABq, J = 10.7 Hz, ArCH2), 4.88
1
Colorless syrup; Rf 0.37 (3/5/3 hexane–chloroform/ether); H
NMR (CDCl3, TMS) d 8.01 (2H, dd, Jo,m = 8.3 Hz, Jo,p = 1.5 Hz,
Ho of Bz), 7.55 (1H, tt, Jm,p = 6.6 Hz, Jo,p = 1.5 Hz, Hp of Bz), 7.42
(2H, dd, Jo,m = 8.3 Hz, Jm,p = 6.6 Hz, Hm of Bz), 7.29-7.19 (5H, m,
ArH), 6.90 (1H, dd, J2,3 = 10.2 Hz, J1,2 = 3.7 Hz, H-2), 6.54 (1H, d,
J1,2 = 3.7 Hz, H-1), 6.19 (1H, d, J2,3 = 10.2 Hz, H-3), 4.71 (1H, dd,
J5,6 = 5.6 Hz, J5,6 = 2.2 Hz, H-5), 4.66-4.53 (1H, m, H-6¢), 4.61 &
4.45 (2H, ABq, J = 11.5 Hz, ArCH2), 4.57 (1H, dd, J1,2 = 9.2 Hz,
J1,2 = 2.4 Hz, H-1¢), 4.51-4.44 (1H, m, H-6¢), 4.30 (1H, dd, J6,6
11.7 Hz, J5,6 = 2.2 Hz, H-6), 3.92 (1H, dd, J6,6 = 11.7 Hz, J5,6
5.6 Hz, H-6), 3.73 (1H, ddd, J4¢,5¢ = 9.0 Hz, J5¢,6¢ = 6.0 Hz, J5¢,6¢
=
=
=
& 4.60 (2H, ABq, J = 11.2 Hz, ArCH2), 4.79 (1H, dd, J1¢¢,2¢¢
=
8.8 Hz, J1¢¢,2¢¢ = 2.7 Hz, H-1¢¢), 4.76 & 4.64 (2H, ABq, J = 11.9 Hz,
ArCH2), 4.63-4.57 (1H, m, H-6¢), 4.62 (1H, d, J1,2 = 3.4 Hz, H-
1), 4.60 & 4.22 (2H, ABq, J = 11.5 Hz, ArCH2), 4.23 (1H, dd,
J5¢¢,6¢¢ = 5.6 Hz, J5¢¢,6¢¢ = 3.2 Hz, H-5¢¢), 4.07 (1H, dd, J6¢¢,6¢¢ = 11.0 Hz,
J5¢¢,6¢¢ = 5.6 Hz, H-6¢¢), 4.09-3.99 (2H, m, H-6 & H-5¢), 3.99 (1H,
3.0 Hz, H-5¢), 3.45 (1H, m, H-4¢), 2.08 (3H, s, OAc), 2.35-2.25
(1H, m, H-3¢), 1.95-1.91 (1H, m, H-2¢), 1.65-1.51 (2H, m, H-2¢ &
H-3¢). This compound was found to be too unstable to precisely
measure other data, and easily epimerized to the corresponding a
anomer.
dd, J2,3 = J3,4 = 9.2 Hz, H-3), 3.82 (1H, dd, J6¢¢,6¢¢ = 11.0 Hz, J5¢¢,6¢¢
3.2 Hz, H-6¢¢), 3.77-3.73 (2H, m, H-5, H-6), 3.55 (1H, dd, J3,4
=
=
J4,5 = 9.2 Hz, H-4), 3.51-3.41 (3H, m, H-2, H-4¢ & H-6¢), 3.31
(3H, s, OMe), 2.02 (1H, m, H-3¢¢), 1.88-1.63 (3H, m, H-2¢¢ ¥ 2
& H-3¢¢); 13C NMR (CDCl3) d 193.71, 166.45, 146.60, 138.70,
138.39, 138.09, 132.76, 130.30, 129.71, 128.93, 128.45, 128.37,
128.24, 128.11, 128.01, 127.88, 127.76, 127.68, 127.63, 98.01,
96.16, 95.87, 82.17, 79.80, 78.12, 77.15, 75.75, 74.76, 73.27, 72.59,
70.37, 70.26, 69.60, 67.26, 66.00, 64.32, 55.19, 28.72, 23.70; HRMS
(ESI-TOF) m/z 937.3763 (937.3775 calcd for C54H54O14Na,
[M+Na]+).
Methyl 6-O-(6¢-O-benzoyl-6¢-O-(6¢¢-O-benzoyl-4¢¢-benzyl-2¢¢,3¢¢-
dideoxy-a-D-erythro-hex-2-enopyranosyl)-2¢,3¢-dideoxy-D-glycelo-
hex-2¢-enopyranos-4¢-ulosyl)-2,3,4-tri-O-benzyl-a-D-
glucopyranoside (27)
A suspension of disaccharide 26a (22.6 mg, 0.0443 mmol),
methyl 2,3,4-tri-O-benzyl-a-D-glucopyranoside (10) (10.3 mg,
3176 | Org. Biomol. Chem., 2010, 8, 3164–3178
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
General glycosylation procedure in Fig. 3
3.0 Hz, J1,3 = 0.3 Hz, H-1), 4.70 & 4.53 (2H, ABq, J = 12.0 Hz,
ArCH2), 4.57 (1H, dd, J6,6 = 12.0 Hz, J5,6 = 2.1 Hz, H-6), 4.48
A suspension of 2,3-unsaturated glycosyl donor 30 or 33
(0.10 mmol), an alcohol 28 or 29 (0.09 mmol) and MS 5A (100 wt%
to glycosyl donor) in dry CH2Cl2 (40 mL mg-1 to glycosyl donor)
was stirred for 30 min at 25 ◦C, then to the suspension was added
Yb(OTf)3 (68.2 mg, 0.110 mmol) at the temperature listed in Fig. 3.
After the suspension was stirred for the period listed in Fig. 3,
to the mixture was added triethylamine (27.9 mL, 0.200 mmol),
followed by warming to 25 ◦C. The resulting mixture was poured
into saturated NaHCO3 aq., and extracted with EtOAc. The
combined organic layers were washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. Purification of
the residue by flash silica-gel column chromatography gave the
corresponding glycosides.
(1H, dd, J6,6 = 12.0 Hz, J5,6 = 5.4 Hz, H-6), 4.26 (1H, ddd, J4,5
9.3 Hz, J5,6 = 5.4 Hz, J5,6 = 2.1 Hz, H-5), 4.06 (1H, ddd, J4,5
=
=
9.3 Hz, J3,4 = 3.0 Hz, J2,4 = 1.5 Hz, H-4), 1.26 (9H, s, t-Bu). Anal.
Calcd for C24H28O5: C, 72.70; H, 7.12. Found: C, 72.53; H, 6.90.
32b: Colorless syrup; Rf 0.55 (4/1 hexane/acetone); [a]2D8 +123.5
(c 0.20, CHCl3); 1H NMR (CDCl3, TMS) d 8.01 (2H, dd, Jo,m
7.5 Hz, Jo,p = 1.2 Hz, Ho of Bz), 7.57 (1H, tt, Jm,p = 7.5 Hz, Jo,p
=
=
1.2 Hz, Hp of Bz), 7.42 (2H, dd, Jo,m = 7.5 Hz, Jm,p = 7.5 Hz, Hm of
Bz), 7.35-7.20 (5H, m, ArH of Bn), 6.06 (1H, ddd, J2,3 = 10.2 Hz,
J1,3 = 2.1 Hz, J3,4 = 2.1 Hz, H-3), 5.77 (1H, ddd, J2,3 = 10.2 Hz,
J1,2 = 1.5 Hz, J2,4 = 0.9 Hz, H-2), 5.36 (1H, dd, J1,3 = 2.1 Hz,
J1,2 = 1.5 Hz, H-1), 4.66 & 4.56 (2H, ABq, J = 11.7 Hz, ArCH2),
4.55 (1H, dd, J6,6 = 11.4 Hz, J5,6 = 4.2 Hz, H-6), 4.48 (1H, dd,
J6,6 = 11.4 Hz, J5,6 = 5.7 Hz, H-6), 4.07 (1H, ddd, J4,5 = 6.9 Hz,
J5,6 = 5.7 Hz, J5,6 = 4.2 Hz, H-5), 4.03 (1H, ddd, J4,5 = 6.9 Hz,
J3,4 = 2.1 Hz, J2,4 = 0.9 Hz, H-4), 1.27 (9H, s, t-Bu). Anal. Calcd
for C24H28O5: C, 72.70; H, 7.12. Found: C, 72.44; H, 7.15.
1-Adamantyl 4-O-benzyl-6-O-benzoyl-2,3-dideoxy-D-erythro-hex-
2-enopyranoside (31)
31a:. White solids; m.p. 89.3–90.3 ◦C (CHCl3–hexane); Rf
0.75 (2/1 hexane–EtOAc); [a]3D0 +95.4 (c 2.57, CHCl3); 1H NMR
(CDCl3, TMS) d 8.02 (2H, dd, Jo,m = 7.8 Hz, Jo,p = 1.5 Hz, Ho of
Bz), 7.54 (1H, tt, Jm,p = 7.8 Hz, Jo,p = 1.5 Hz, Hp of Bz), 7.40 (2H,
dd, Jo,m = 7.8 Hz, Jm,p = 7.8 Hz, Hm of Bz), 7.35-7.18 (5H, m, ArH
of Bn), 6.10 (1H, ddd, J2,3 = 9.9 Hz, J3,4 = 3.0 Hz, J1,3 = 0.6 Hz,
H-3), 5.74 (1H, ddd, J2,3 = 9.9 Hz, J1,2 = 2.7 Hz, J2,4 = 1.5 Hz,
H-2), 5.40 (1H, dd, J1,2 = 2.7 Hz, J1,3 = 0.6 Hz, H-1), 4.70 & 4.53
(2H, ABq, J = 11.7 Hz, ArCH2), 4.57 (1H, dd, J6,6 = 11.7 Hz,
J5,6 = 2.1 Hz, H-6), 4.47 (1H, dd, J6,6 = 11.7 Hz, J5,6 = 6.6 Hz,
H-6), 4.31 (1H, ddd, J4,5 = 9.6 Hz, J5,6 = 6.6 Hz, J5,6 = 2.1 Hz,
H-5), 4.01 (1H, ddd, J4,5 = 9.6 Hz, J3,4 = 3.0 Hz, J2,4 = 1.5 Hz, H-
4), 2.08-1.98 (3H, m, CH of adamantyl), 1.89-1.74 (6H, m, CH2 ¥
3 of adamantyl), 1.62-1.46 (6H, m, CH2 ¥ 3 of adamantyl). Anal.
Calcd for C30H34O5: C, 75.92; H, 7.22. Found: C, 75.97; H, 7.01.
31b: Colorless syrup; Rf 0.45 (4/1 hexane/acetone); [a]2D9 +86.0
1-Adamantyl 4-O-benzoyl-2,3,6-trideoxy-a-L-threo-hex-2-
enopyranoside (34)
Colorless syrup; Rf 0.73 (2/1 hexane–EtOAc); [a]2D8 +183.0 (c 1.45,
CHCl3); 1H NMR (CDCl3, TMS) d 8.08 (2H, dd, Jo,m = 7.5 Hz,
Jo,p = 1.2 Hz, Ho of Bz), 7.56 (1H, tt, Jm,p = 7.5 Hz, Jo,p = 1.2 Hz,
Hp of Bz), 7.43 (2H, dd, Jo,m = 7.5 Hz, Jm,p = 7.5 Hz, Hm of Bz),
6.17 (1H, ddd, J2,3 = 9.9 Hz, J3,4 = 5.4 Hz, J1,3 = 0.6 Hz, H-3),
5.97 (1H, ddd, J2,3 = 9.9 Hz, J1,2 = 3.3 Hz, J2,4 = 0.6 Hz, H-2),
5.52 (1H, dd, J1,2 = 3.3 Hz, J1,3 = 0.6 Hz, H-1), 5.15 (1H, ddd,
J3,4 = 5.4 Hz, J4,5 = 2.4 Hz, J2,4 = 0.6 Hz, H-4), 4.46 (1H, qd, J5,6
=
6.6 Hz, J4,5 = 2.4 Hz, H-5), 2.21-2.12 (3H, m, CH of adamantyl),
1.95-1.81 (6H, m, CH2 ¥ 3 of adamantyl), 1.71-1.59 (6H, m, CH2 ¥
3 of adamantyl), 1.28 (3H, d, J5,6 = 6.6 Hz, H-6). Anal. Calcd for
C23H28O4: C, 74.97; H, 7.66. Found: C, 74.75; H, 7.62.
(c 0.16, CHCl3); 1H NMR (CDCl3, TMS) d 8.02 (2H, dd, Jo,m
7.5 Hz, Jo,p = 1.2 Hz, Ho of Bz), 7.55 (1H, tt, Jm,p = 7.5 Hz,
Jo,p = 1.2 Hz, Hp of Bz), 7.42 (2H, dd, Jo,m = 7.5 Hz, Jm,p
=
tert-Butyl 4-O-benzoyl-2,3,6-trideoxy-a-L-threo-hex-2-
enopyranoside (35)
=
7.5 Hz, Hm of Bz), 7.35-7.21 (5H, m, ArH of Bn), 6.06 (1H, ddd,
J2,3 = 10.2 Hz, J3,4 = 2.4 Hz, J1,3 = 1.8 Hz, H-3), 5.78 (1H, ddd,
J2,3 = 10.2 Hz, J1,2 = 1.8 Hz, J2,4 = 1.2 Hz, H-2), 5.48 (1H, dd,
J1,2 = 1.8 Hz, J1,3 = 1.8 Hz, H-1), 4.66 & 4.56 (2H, ABq, J =
11.7 Hz, ArCH2), 4.54 (1H, dd, J6,6 = 11.4 Hz, J5,6 = 3.9 Hz, H-6),
4.48 (1H, dd, J6,6 = 11.4 Hz, J5,6 = 6.3 Hz, H-6), 4.08 (1H, ddd,
J4,5 = 6.3 Hz, J5,6 = 6.3 Hz, J5,6 = 3.9 Hz, H-5), 4.02 (1H, ddd,
J4,5 = 6.3 Hz, J3,4 = 2.4 Hz, J2,4 = 1.2 Hz, H-4), 2.14-2.04 (3H, m,
CH of adamantyl), 1.91-1.74 (6H, m, CH2 ¥ 3 of adamantyl), 1.66-
1.50 (6H, m, CH2 ¥ 3 of adamantyl). Anal. Calcd for C30H34O5:
C, 75.92; H, 7.22. Found: C, 75.94; H, 7.21.
Colorless syrup; Rf 0.83 (2/1 hexane–EtOAc); [a]2D8 +196.7 (c 1.26,
CHCl3); 1H NMR (CDCl3, TMS) d 8.09 (2H, dd, Jo,m = 7.2 Hz,
Jo,p = 1.5 Hz, Ho of Bz), 7.56 (1H, tt, Jm,p = 7.2 Hz, Jo,p = 1.5 Hz,
Hp of Bz), 7.43 (2H, dd, Jo,m = 7.2 Hz, Jm,p = 7.2 Hz, Hm of Bz),
6.17 (1H, ddd, J2,3 = 9.9 Hz, J3,4 = 5.4 Hz, J1,3 = 0.6 Hz, H-3), 5.98
(1H, dd, J2,3 = 9.9 Hz, J1,2 = 3.3 Hz, H-2), 5.39 (1H, dd, J1,2
3.3 Hz, J1,3 = 0.6 Hz, H-1), 5.16 (1H, dd, J3,4 = 5.4 Hz, J4,5
=
=
2.7 Hz, H-4), 4.44 (1H, qd, J5,6 = 6.6 Hz, J4,5 = 2.7 Hz, H-5), 1.32
(9H, s, t-Bu), 1.28 (3H, d, J5,6 = 6.6 Hz, H-6). Anal. Calcd for
C17H22O4: C, 70.32; H, 7.64. Found: C, 70.20; H, 7.57.
tert-Butyl 4-O-benzyl-6-O-benzoyl-2,3-dideoxy-D-erythro-hex-2-
1-Adamantyl 4-O-benzoyl-2,3,6-trideoxy-a-L-threo-
enopyranoside (32)
hexopyranoside (38)
32a:. Colorless syrup; Rf 0.63 (4/1 hexane/acetone); [a]D28
+105.3 (c 1.78, CHCl3); H NMR (CDCl3, TMS) d 8.00 (2H,
Colorless syrup; Rf 0.83 (2/1 hexane–EtOAc); [a]3D0 -38.5 (c 0.74,
CHCl3); 1H NMR (CDCl3, TMS) d 8.12 (2H, dd, Jo,m = 7.2 Hz,
Jo,p = 1.5 Hz, Ho of Bz), 7.57 (1H, tt, Jm,p = 7.5 Hz, Jo,p = 1.5 Hz,
Hp of Bz), 7.44 (2H, dd, Jm,p = 7.5 Hz, Jo,m = 7.2 Hz, Hm of Bz),
5.37 (1H, br-ddd, J3ax,4 = 3.9 Hz, J4,5 = 1.5 Hz, H-4), 5.04 (1H,
1
dd, Jo,m = 7.2 Hz, Jo,p = 1.5 Hz, Ho of Bz), 7.55 (1H, tt, Jm,p
=
7.2 Hz, Jo,p = 1.5 Hz, Hp of Bz), 7.41 (2H, dd, Jo,m = 7.2 Hz, Jm,p
=
7.2 Hz, Hm of Bz), 7.35-7.17 (5H, m, ArH of Bn), 6.10 (1H, ddd,
J2,3 = 9.9 Hz, J3,4 = 3.0 Hz, J1,3 = 0.3 Hz, H-3), 5.74 (1H, ddd,
br-dd, J1,2ax = 2.7 Hz, H-1), 4.33 (1H, qd, J5,6 = 6.6 Hz, J4,5 =
J2,3 = 9.9 Hz, J1,2 = 3.0 Hz, J2,4 = 1.5 Hz, H-2), 5.29 (1H, dd, J1,2
=
1.5 Hz, H-5), 2.23 (1H, dddd, J2ax,3ax = 13.5 Hz, J2ax,2eq = 13.5 Hz,
Org. Biomol. Chem., 2010, 8, 3164–3178 | 3177
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
J2ax,3eq = 4.2 Hz, J1,2ax = 2.7 Hz, H-2ax), 2.19-2.11 (3H, m, CH of
adamantyl), 2.03 (1H, dddd, J2ax,3ax = 13.5 Hz, J3ax,3eq = 13.5 Hz,
J2eq,3ax = 3.9 Hz, J3ax,4 = 3.9 Hz, H-3ax), 1.91-1.77 (6H, m, CH2 ¥
1999, 52, 269; (c) N. Matsumoto, T. Tsuchida, H. Nakamura, R. Sawa,
Y. Takahashi, H. Naganawa, H. Iinuma, T. Sawa, T. Takeuchi and M.
Shiro, J. Antibiot., 1999, 52, 276.
7 A. Kawashima, Y. Kishimura, M. Tamai and K. Hanada, Chem.
Pharm. Bull., 1989, 37, 3429.
8 A. Sobti, K. Kim and G. A. Sulikowski, J. Org. Chem., 1996, 61, 6.
9 (a) W. P. Jencks, In Catalysis in Chemistry and Enzymology, Dover
Publishers, Inc., New York, 1987, pp. 302–305; (b) N. C. J. Strynadka
and M. N. G. James, J. Mol. Biol., 1991, 220, 401.
10 (a) L. O. Ford, L. N. Johnson, P. A. Machin, D. C. Phillips and R.
Tjian, J. Mol. Biol., 1974, 88, 349; (b) C. M. Chipman and N. Sharon,
Science, 1969, 165, 454; (c) D. M. Chipman, Biochemistry, 1971, 10,
1714; (d) J. A. Rupley, Proc. R. Soc. London, Ser. B, 1967, 167, 416; (e) I.
Imoto, L. N. Johnson, A. C. T. North, D. C. Phillips and J. A. Rupley,
In The Enzymes, ed. P. Boyer, Academic Press, New York, 1972, 3rd
ed., vol. 7, pp. 665–868.
3 of adamantyl), 1.89 (1H, br-dddd, J2ax,2eq = 13.5 Hz, J2eq,3eq
=
6.6 Hz, J2eq,3ax = 3.9 Hz, H-2eq), 1.71-1.57 (6H, m, CH2 ¥ 3 of
adamantyl), 1.46(1H, br-dddd, J3ax,3eq = 13.5 Hz, J2eq,3eq = 6.6 Hz,
J2ax,3eq = 4.2 Hz, H-3eq), 1.15 (3H, d, J5,6 = 6.6 Hz, H-6). Anal.
Calcd for C23H30O4: C, 74.56; H, 8.16. Found: C, 74.24; H, 8.24.
Acknowledgements
This research was supported in part by a Grant-in-Aid for the
21st Century Center of Excellence (COE) Program ‘KEIO Life
Conjugated Chemistry¢, for the Scientific Research on Priority
Areas 18032068, for the JSPS Fellows 18·6013, and for the High-
Tech Research Center Project for Private Universities: Matching
Fund Subsidy, 2006-2011, from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan (MEXT).
11 (a) F. W. Dahlquist, T. Rand-Meir and M. A. Raftery, Biochemistry,
1969, 8, 4214; (b) L. E. H. Smith, L. H. Mohr and M. A. Raftery,
J. Am. Chem. Soc., 1973, 95, 7497; (c) S. Rosenberg and J. F. Kirsh,
Biochemistry, 1981, 20, 3196.
12 6-Acyl-2H-pyran-3(6H)-one system was effectively used in palladium-
catalyzed glycosylation, see: (a) A. C. Comely, R. Eelkema, A. J.
Minnaard and B. L. Feringa, J. Am. Chem. Soc., 2003, 125, 8714;
(b) R. S. Babu and G. A. O’Doherty, J. Am. Chem. Soc., 2003, 125,
12406; (c) R. S. Babu, M. Zhou and G. A. O’Doherty, J. Am. Chem.
Soc., 2004, 126, 3428; (d) S. R. Guppi, M. Zhou and G. A. O’Doherty,
Org. Lett., 2006, 8, 293; (e) R. S. Babu, S. R. Guppi and G. A.
O’Doherty, Org. Lett., 2006, 8, 1605; (f) M. Zhou and G. A. O’Doherty,
Org. Lett., 2008, 10, 2283; (g) X. Yu and G. A. O’Doherty, Org. Lett.,
2008, 10, 4529; (h) M. Shan, Y. Xing and G. A. O’Doherty, J. Org.
Chem., 2009, 74, 5961.
13 For our preliminary communication on this work, see: (a) K. Sasaki,
S. Matsumura and K. Toshima, Tetrahedron Lett., 2006, 47, 9039;
(b) S. Kusumi, S. Wang, T. Watanabe, K. Sasaki, D. Takahashi and
K. Toshima, Org. Biomol. Chem., 2010, 8, 988.
14 B. Fraser-Reid and B. Boctor, Can. J. Chem., 1969, 47, 393.
15 B. Shanmugasundaram, A. K. Bose and K. K. Balasubramanian,
Tetrahedron Lett., 2002, 43, 6795.
References
1 For selected reviews on synthesis of oligosaccharides, see: (a) J. P.
Kamerling, G.-J. Boons, Y. C. Lee, A. Suzuki, N. Taniguchi and A. G. J.
Voragen, Comprehensive Glycoscience, Elsevier, Oxford, 2007; (b) B. O.
Fraser-Reid, K. Tatsuta, and J. Thiem, Glycosience, Springer, Berlin,
1st ed. 2001 and 2nd ed. 2008; (c) B. Ernst, G. W. Hart and P. Sina¨y,
Carbohydrates in Chemistry and Biology, Wiley-VCH, Weinheim, 2000.
2 For selected reviews on chemoselective glycosylation, see: (a) A. V.
Demchenko, Handbook of Chemical Glycosylation: Advances in Stere-
ochemistry and Therapeutic Relevance, Wiley-VCH, Weinheim, 2008;
(b) H. Tanaka, H. Yamada and T. Takahashi, Trends Glycosci.
Glycotechnol., 2007, 19, 183; (c) G. A. van der Marel, L. J. van den
Bos, H. S. Overkleeft, R. E. J. N. Litjens and J. D. C. Codee, ACS
Symp. Ser., 2007, 960, 190; (d) B. Fraser-Reid, K. N. Jayaprakash, J. C.
Lopez, A. M. Gomez and C. Uriel, ACS Symp. Ser., 2007, 960, 91.
3 D. R. Mootoo, P. Konradsson, U. Udodong and B. Fraser-Reid, J. Am.
Chem. Soc., 1988, 110, 5583.
16 (a) R. J. Ferrier and N. Prasad, J. Chem. Soc., 1969, C, 570; (b) R. J.
Ferrier, Top. Curr. Chem., 2001, 215, 153.
17 (a) K. Sasaki, T. Wakamatsu, S. Matsumura and K. Toshima, Tetrahe-
dron Lett., 2006, 47, 8271; (b) M. H. Haukaas and G. A. O’Doherty,
Org. Lett., 2002, 4, 1771.
4 For a selected review on chemoselective glycosylations for 2-deoxy
sugars, see: K. Toshima and K. Tatsuta, Chem. Rev., 1993, 93, 1503.
5 (a) S. Omura, H. Tanaka, R. Oiwa, J. Awaya, R. Masuma and K.
Tanaka, J. Antibiot., 1977, 30, 908; (b) N. Imamura, K. Kakinuma, N.
Ikekawa, H. Tanaka and S. Omura, J. Antibiot., 1981, 34, 1517.
6 (a) N. Matsumoto, T. Tsuchida, M. Maruyama, R. Sawa, N. Kinoshita,
Y. Homma, Y. Takahashi, H. Iinuma, H. Naganawa, T. Sawa, M.
Hamada and T. Takeuchi, J. Antibiot., 1996, 49, 953; (b) N. Matsumoto,
T. Tsuchida, M. Maruyama, N. Kinoshita, Y. Homma, H. Iinuma, T.
Sawa, M. Hamada, T. Takeuchi, N. Heida and T. Yoshioka, J. Antibiot.,
18 For a typical example, see: K. Toshima, G. Matsuo and M. Nakata,
J. Chem. Soc., Chem. Commun., 1994, 997.
19 (a) For reviews of angucycline group of antibiotics, see: J. Rohr and
R. Thiericke, Nat. Prod. Rep., 1992, 9, 103; (b) M. C. Carreno and A.
˜
Urbano, Synlett, 2005, 1–25.
20 N. Hashizume and S. Kobayashi, Carbohydr. Lett., 1996, 2, 157.
21 B. W. Bycroft, Dictionary of Antibiotics and Related Substances,
Chapman and Hall, New York, 1988.
22 For our preliminary communication on that work, see: K. Sasaki, S.
Matsumura and K. Toshima, Tetrahedron Lett., 2007, 48, 6982.
3178 | Org. Biomol. Chem., 2010, 8, 3164–3178
This journal is
The Royal Society of Chemistry 2010
©