Synthesis of thiosaccharides employing the Pummerer rearrangement of tetrahydrothiopyran oxides

Article abstract of DOI:10.1016/j.tet.2004.06.006

The Pummerer rearrangement of 1-deoxy-5-thioglucopyranose derivatives carrying acetonides at the C3,4-positions proceeded regioselectively at the C1 position by treating with TFAA in the presence of pyridine. Studies employing deuterium-labelled derivatives revealed that the reaction was induced by E2 1,2-elimination of trifluoroacetic acid of the trifluoroacetoxy sulfonium intermediate. This methodology was applied to the synthesis of an isomaltotriose derivative consisting of 5-thioglucopyranoside units.

Full text of DOI:10.1016/j.tet.2004.06.006

Tetrahedron 60 (2004) 6829–6851
Synthesis of thiosaccharides employing the Pummerer
rearrangement of tetrahydrothiopyran oxidesq
†
Junji Fujita,a Hiroko Matsuda,a Kazunori Yamamoto,a Yasuharu Morii,a Masaru Hashimoto,a
,
,
*
Toshikatsu Okunoa and Kimiko Hashimotob
aFaculty of Agriculture and Life Science, Hirosaki University, 3 Bunkyo-Cho, Hirosaki, Aomori 036-8561, Japan
bDepartment of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku,
Yokohama 223-8522, Japan
Received 9 April 2004; revised 2 June 2004; accepted 3 June 2004
Available online 4 July 2004
Abstract—The Pummerer rearrangement of 1-deoxy-5-thioglucopyranose derivatives carrying acetonides at the C3,4-positions proceeded
regioselectively at the C1 position by treating with TFAA in the presence of pyridine. Studies employing deuterium-labelled derivatives
revealed that the reaction was induced by E2 1,2-elimination of trifluoroacetic acid of the trifluoroacetoxy sulfonium intermediate. This
methodology was applied to the synthesis of an isomaltotriose derivative consisting of 5-thioglucopyranoside units.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussions
2.1. Basic methodology
Carbomimetics, analogues which structurally mimic carbo-
hydrates, are candidates not only as potent probes in the
mechanistic investigation of glycosidases but also as novel
drugs for some digestive or infective diseases.1–7 We have
made efforts towards the synthesis of oligosaccharide
derivatives consisting of 5-thiopyranoses based on the
concept that replacement of the oxygens in the pyranose
rings of oligosaccharides with sulfur atoms may realize
tolerance against glycosidases with minimum structural
alterations.8,9 As part of these studies, we have discovered
that the Pummerer rearrangement of thiopyranose oxides
having O-3 and O-4 protected as an O-isopropylidene
derivative proceeded and reported this finding as a
communication.10 Further investigation employing
deuterium-labelled derivatives enabled us to discuss details
of the reaction. Now, we would like to report the details of
these studies and an application of this strategy to a
synthesis of sulfur-substituted isomaltotrioside.
Since the Pummerer rearrangement provides a synthetic
equivalent of carbonyl compounds from sulfoxides, an
equivalent for alcohols, under non-oxidative conditions, it
has been utilized in total syntheses of natural products as an
alternative protocol for oxidation of the alcohols.11,12 This
rearrangement will be desirable for introduction of the C1
hemithioacetal function of thiosugars if we can perform the
rearrangement of 1-deoxy-5-thiopyranose oxides at the C1
position regioselectively as shown in Scheme 1.13 In spite of
extensive studies by Oae14,15 and Crucianelli16 on the
Pummerer rearrangements, the regioselectivity for
highly functionalized asymmetric sulfoxides has not
been fully discussed. Recently, Naka et al.17,18 and Zhang
et al.19 independently investigated regio- and stereo-
selective formation of thionucleosides via Pummerer-type
q Supplementary data associated with this article can be found in the online
version, at doi:10.1016/j.tet.2004.06.006
Keywords: Thiosaccharids; Pummerer rearrangements; Reaction
mechanism; Isomaltotriose analogue.
*
Corresponding author. Tel./fax: þ81-172-39-3782;
e-mail address: hmasaru@cc.hirosaki-u.ac.jp
Present address: Department of Chemistry, Columbia University, 3000
Broadway, NYC, NY 10027, USA.
†
Scheme 1. Basic strategy.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.06.006

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J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
glycosidation. However, the factors determining regio-
selectivity have not been fully elucidated. Thus, we had to
study the reaction courses caused by the differences in the
stereochemistry of the sulfoxides and in the protective
groups at the C2–C6 positions in the rearrangement.
2.2. Preparation of 1-deoxy-5-thio-D-glucopyranose
oxides
We first synthesized axial and equatorial oxides of 1-deoxy-
5-thioglucopyranoses carrying a series of protective groups
9-12 (Scheme 2). Thiane 4 was readily prepared from
D-mannitol following the protocol reported by Merrer et al.20
The hydroxy group of 4 was protected in the form of
methoxymethyl (MOM) ether under usual conditions to give
5 in 86% yield. The sulfide function of 5 was oxidized to the
sulfoxide with m-chloroperbenzoic acid (mCPBA) in
CH2Cl2 at 220 8C for 30 min. This oxidation proceeded
without stereoselectivity, giving a separable mixture (50:50)
of the axial- and equatorial-sulfoxides, ax-9 and eq-9, in
87% yield. In a similar manner, 4 was converted into the
benzoates ax-10 and eq-10 in good overall yield. Benzoyl-
ation after removal of the acetonide of 4 gave 7 in 85% yield
in two steps. The acetonide group of 4 migrated to the C2–
C3 positions (carbohydrate numbering) by treatment of 4
with p-toluenesulfonic acid in acetone to afford 8a (60%)
along with recovery of 4 (32%). The hydroxy function of 8a
was protected as the acetate, giving 8b in quantitative yield.
In a similar manner described for 9 and 10, sulfides 7 and 8b
were converted into both isomeric mixtures of sulfoxides 11
and 12, respectively. Those isomers could also be readily
separated by silica gel column chromatography.
i
Scheme 2. Reagents and conditions: (a) for 5; MOMCl, Pr2NEt, CH2Cl2,
0 8C (86%), for 6; BzCl, pyridine, rt (95%); (b) (i) cat. HCl, MeOH, rt
(85%), (ii) BzCl, pyridine, rt (100%); (c) (i) cat. p-TsOH, rt, acetone, then
separation, (ii) Ac2O, pyridine, rt (100%); (d) mCPBA, CH2Cl2, 220 8C (9,
87%, 10, 91%, 11, 96%, 12, 92%, isomeric ratios (eq/ax) 9: (50:50), 10:
(60:40), 11: (50:50), 12: (60:40).
selectivity in the Pummerer rearrangements, assignment of
those stereochemistries was required. In the 1H NMR
spectra of both isomers of 9-12, large coupling constants for
JC1Hax,C2H, JC2H,C3H, JC3H,C4H, and JC4H,C5H (carbohydrate
numbering) of the tetrahydrothiopyran ring moieties
2.3. Stereochemistry of the sulfoxides
Stereochemistries of the sulfoxide moieties of 9-12 were
next studied. Since there were few precedents regarding the
effect of stereochemistry of sulfoxides on the regio-
Table 1. The characteristic 1H- and 13C NMR chemical shifts of sulfoxides 9-12 and their differences Dd (vd(eq)2d(ax), italic) and the coupling constants for
JC1Heq–C1Hax and JC5H–C6H
Signals
9a
10a
11b
12a
eq
ax
Dd
eq
ax
Dd
eq
ax
Dd
eq
ax
Dd
C1Hax
C1Heq
C2H
C5H
C1
2.75
3.32
3.63
2.69
1.69
3.20
4.62
2.53
þ1.06
þ0.12
20.99
þ0.16
þ4.8
2.66
3.24
5.32
2.82
1.58
3.33
6.13
2.65
þ1.08
20.09
20.81
þ0.17
þ4.2
3.22
4.02
5.45
3.49
2.72
3.85
6.10
3.38
þ0.50
þ0.17
20.65
þ0.11
þ5.2
2.55
3.28
3.05
2.73
1.63
3.03
4.61
2.52
þ0.92
þ0.25
21.56
þ0.21
þ4.1
55.4
50.6
53.4
49.2
52.6
47.4
52.2
48.1
C2
69.2
71.0
64.2
71.1
72.7
58.8
21.9
67.8
71.4
64.8
69.3
72.9
59.2
21.5
65.3
64.8
65.7
67.3
67.9
59.0
22.0
69.1
65.0
67.0
71.6
68.9
60.6
22.5
C4
21.7
21.5
23.1
23.9
C5
þ5.4
þ5.6
þ6.7
þ6.4
JC1Heq–C1Hax
12.2
14.6
12.7
14.1
11.8
14.2
10.7
13.2
3.0
4.4
4.4
11.7
3.4
5.4
4.4
11.2
2.5
2.5
4.9
9.3
3.0
4.8
3.9
9.8
JC5H–C6H
a
Observed in C6D6.
Observed in CDCl3.
b

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6831
suggested that those protons are in axial orientations. Thus,
4
the tetrahydrothiopyran rings of isomers 9-12 adopt C1
1
conformations. The characteristic signals in their H- and
13C NMR spectra are shown in Table 1. Signs of the Dd
value [¼d(eq-isomer)2d(ax-isomer)] are consistent with
the literature21 without exception about the C2H, C4H, and
1
C5H signals in the H NMR spectra as well as resonances
due to C1, C2, C4, and C5 in the 13C NMR spectra. The
coupling constants, JC1Heq–C1Hax (geminal coupling), for
axial sulfoxides ax-9-12 were larger than those of the
corresponding equatorial isomers eq-9-12, which also
supported those stereochemistries according to Eliel’s
report.22–24
Figure 2. Estimated chemical shifts (ppm) of the a-methylene protons of
thiane and its oxides.25
The conditions using trifluoroacetic anhydride (TFAA) in
place of Ac2O, the modified protocol developed by one of
present authors,12 was found to promote the rearrangement
smoothly at room temperature. Thus, the treatment of eq-9
with TFAA (5.0 equiv.) in the presence of pyridine
(10 equiv.) in CH2Cl2 at room temperature for 3 h realized
the rearrangement in highly stereoselective manner, provid-
ing 5-thioglucopyranose derivative 15 as shown in
Scheme 3. The trifluoroacetyl group introduced was
hydrolyzed during the work-up. The existence of the OH
group in 15 was confirmed by observing strong absorption at
3440 cm21 (broad) in the IR spectrum. The 1H NMR
spectrum indicated that 15 exists as a 90:10 anomeric
mixture. Since 15 appeared as a broad spot on the TLC due
to the equilibrium between the anomers, the accurate yield
of 15 after silica gel column chromatography in this reaction
could not be obtained. It was estimated to be 66% after
acetylation, giving an anomeric mixture (a/b¼34:66) of 16.
Those isomers could be separated by preparative silica gel
TLC. The structure of 16 was confirmed after converting it
into pentabenzoate 17. Treatment of the a-isomer of 16 with
aqueous trifluoroacetic acid promoted hydrolysis of the
acetonide and the C1 acetyl group. The following
benzoylation under usual conditions gave 17 as an
inseparable mixture (a/b¼80:20) in 63% yield in two
steps. The 1H NMR spectrum of this sample was identical,
except for the isomeric ratio, with that of 17 prepared from
5-thioglucopyranosyl peracetate 1830 by saponification and
the subsequent benzoylation. The isomeric ratio of 17
prepared from 18 was a/b¼90:10.
The stereochemistries of these sulfoxides were studied
further. In the axial sulfoxide (ax-isomer), the electron-
donating oxide moiety should shield the anti-periplanar-
orientated axial proton (C1Hax) of the C1 position as shown
in Figure 122,25,26 In contrast, the lone pair electrons of the
equatorial sulfoxide (eq-isomer) did not induce the above
effect for the C1Hax. This suggested that the signs of the Dd
values for C1Hax should be positive. On the other hand, the
Dd values for the C1Heq are expected to be small, since the
sulfoxide moiety equally affected those protons because of
the gauche relationships between the oxygen of the
sulfoxides and the C1 equatorial protons for both axial
and equatorial sulfoxides. The observed Dd values for the
C1Heq accorded with the discussion. These Dd values were
also supported by theoretical calculations for tetra-
hydrothiopyran oxides employed as the model molecules.
The estimated chemical shifts for the C1 methylene protons
(carbohydrate numbering) of the axial thiane oxide ax-14
and the corresponding equatorial isomer eq-14 are shown in
Figure 2. These chemical shifts were calculated using
Spartan 04.27 Optimization of these structures was
performed prior to the calculations of their chemical shifts.
In order to take the contribution of the d-orbitals of the
sulfur atoms into account, the 6-31G* basis set28 was
employed for these computations. The chemical shifts of
the C1Hax (carbohydrate numbering) in the axial isomer
ax-14 was predicted to appear at higher field than those of
the corresponding equatorial isomer eq-14 and sulfide 13.
The rearrangements for other congeners eq-10-12 were also
2.4. The Pummerer rearrangement of sulfoxides 9-12
With the sulfoxides 9-12 in hand, Pummerer rearrangements
were attempted. The rearrangement did not proceed at room
temperature when acetic anhydride (Ac2O) was
employed.29 The heating conditions with Ac2O resulted in
the formation of complex mixtures in the cases that both ax-
and eq-11 were employed. Preparative TLC after refluxing
ax-9 and Ac2O in pyridine gave only trace amounts of 15
and thiane 5.
Scheme 3. The Pummerer rearrangement of eq-9. Reagents and conditions:
(a) TFAA, Py, CH2Cl2, rt; (b) Ac2O, Py, rt, then separation (66% two
steps); (c) (i) aq. TFA, rt, (ii) BzCl, Py, rt (63% two steps); (d) (i) NaOMe,
MeOH, rt, (ii) BzCl, Py, rt (67% two steps).
Figure 1. Shielding and deshielding of the C1 protons by the sulfoxide
oxygen.

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J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
Table 2. Products obtained by Pummerer rearrangement of sulfoxides 9-12
Run
Sulfoxides
5-Thioglucose derivatives (a/b, yields)
Other products
1
2
3
4
5
6
7
8
9
10
eq-9
ax-9
15 (34:66, 66%)a
15 (34:66, 84%)a
20 (91:9, 55%)
20 (90:10, 61%)
20 (90:10, 66%)c
20 (90:10, 65%)c
24 (90:10, 5.7%)
24 (90:10, 2.7%)
29 (not detected)
29 (not detected)
Not detected
19b (trace)
eq-10
ax-10
eq-10
ax-10
eq-11
ax-11
eq-12
ax-12
21, 22, 23 (trace each)b
21, 22, 23 (trace each)b
Not detected
Not detected
25 (4.0%), 26 (50%), 27 (8.9%)d, 28 (9.5%)
25 (0.3%), 26 (41%), 27 (5.6%)d, 28 (8.9%)
30 (14%), 31 (40%), 32 (1.7%)d
30 (9.4%), 31 (45%), 32 (1.2%)d
a
The isomeric ratio and yield were determined after acetylation (!16).
b
c
d
1
Structures of minor 19, 21, 22, and 23 were assigned by comparing those H NMR spectra with those of the corresponding compounds 25-32.
Pyridine was employed as the solvent.
Structures of 27 and 32 were estimated based on the product obtained by treating with Et3N in methanol.
investigated. The results are summarized in Table 2. In the
reaction of eq-10, carrying benzoate in place of the MOM
group of 9, the rearrangement occurred in similar selectivity
to that of 9, giving 5-thioglucopyranose derivative 20 in
55% yield along with trace amounts of other products 21-23
(run 3). Products 21-23 were obtained via the rearrangement
to the C5 position. The structures of 21-23 could not be fully
determined because of their trace amounts; however, those
were tentatively assigned by comparing their 1H NMR
spectra with those of 25-32 (vide infra). An attempt
employing pyridine as the solvent slightly improved the
yield of desired 20 (run 5).
stereochemistry of 26 was tentatively assigned as 5R
(carbohydrate numbering) taking the anomeric effect into
account. exo-Olefin 25 was obtained as a single isomer, but
assignment of the stereochemistry for the C5–C6 double
bond has remained unclear.
Notably, when 2,3-O-acetonide eq-12 was subjected to the
Pummerer reaction, the rearrangement proceeded with
higher regioselectivity at the C5 position (carbohydrate
numbering) to give a mixture of 30-32 (run 9). Thiogluco-
pyranose 29, obtainable through the rearrangement at the C1
position, was not observed under these conditions.
In contrast, the rearrangement for perbenzoate eq-11
proceeded at the C5 position predominantly to give
undesired 5-hydroxy derivative 26 (50%), the correspond-
ing trifluoroacetate 27 (8.9%), exo-olefin 25 (4.0%), and
endo-olefin 28 (9.5%) (run 7). 5-Thioglucose derivative 24
was obtained as a minor product (5.7%) by this experiment.
Interestingly, anomers a-24 and b-24 could be separated by
silica gel column chromatography, whereas the correspond-
ing anomers of 15 were inseparable due to equilibration.
Trifluoroacetate 27 was not stable enough to obtain its
spectral data; however, two-dimensional silica gel TLC
analysis of 27 disclosed that 27 was easily transformed into
the corresponding alcohol 26. This observation suggested
that 27 was a trifluoroacetate ester of 26. Alcohol 26 was
produced as a single isomer at C5; the stereochemistry of 26
and 27, however, could not be assigned by NOE studies. The
Axial sulfoxides ax-9-12 were also subjected to the
Pummerer reaction under similar conditions (run 2, 4, 6,
8, and 10). The same products as those provided from the
corresponding equatorial sulfoxides were afforded in similar
yields. Noteworthily, ax-9 gave 16 in 84% yield after
acetylation. It seems that the stereochemistry of the
sulfoxide moiety is not important for the regioselectivity
in the rearrangement based on these observations. This is
inconsistent with Naka’s report,17 disclosing the stereo-
chemistry of sulfoxides contributes significantly to the
regioselectivity, although TMSOTf was used as the
activator.
The regioselectivities are next discussed. Acetonides 9 and
10 carry an electron-withdrawing benzoate ester and an
electron-donating MOM ether, respectively, at their C2

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6833
positions (carbohydrate numbering). These protective
groups were expected to affect the stability of the cationic
intermediates produced during the Pummerer rearrange-
ment. However, 9 and 10 provided similar results.
Accordingly, an electrostatic factor might contribute less
to the regioselectivity. On the other hand, the position of the
acetonide group dramatically influenced the selectivity as
mentioned above. Thus, the relationship between the
selectivity and the conformation of the ring moieties of
9-12 was investigated using molecular modeling calcu-
lations.31 Model compounds X, Y, and Z were selected in
order to save the time required for the calculations. Since
these model compounds involve sulfoxide functions, an ab
initio method based on the 6-31Gp basis set was employed.
The results are summarized in Table 3.
although O-acyl function at C2 contributes for the
b-addition in regular carbohydrate chemistry.
2.5. Mechanistic studies on the Pummerer reaction
2.5.1. Preparation of deuterium-labelled sulfoxides ax-41
and eq-41. Exposing the sulfoxide eq-10 to the Pummerer
conditions (TFAA, Py-CH2Cl2), at a lower temperature
(0 8C) for a shorter period (20 min) afforded the ax-10 in
60% yield along with the rearranged product 20 (27%). This
observation suggests the occurrence of epimerization of the
sulfoxide moiety under the conditions we employed. Oae
et al. reported mechanistic details about the Pummerer
rearrangement of thianes;14 however, epimerization of the
sulfoxide moiety during the Pummerer reaction was not
mentioned. Thus, there might be some difference in the
reaction pathways from that which they reported. In order to
examine the reaction details, the Pummerer rearrangement
employing both isomers of deuterium-labelled derivatives
ax- and eq-41 was next attempted.
In the cases of bicyclic Y and Z, the annular bond angles of
the carbons, where the rearrangement occurs mainly in the
experiments (/S–C5–C4 for Y, /S–C1–C2 for Z), were
suggested to be around 1158. This angle approximates that
of sp2 carbons. Thus, these carbons can be easily
transformed to the planar sp2 thiocarbenium intermediate.
On the other hand, the angles for the other sites (/S–C1–
C2 for Y, /S–C5–C4 for Z) were estimated to be around
1058, which is rather small comparing to that of the standard
sp3 carbon. So, these carbons might remain intact during the
reactions. While there was no remarkable difference
between the angles /S–C1–C2 and /S–C5–C4 for
monocyclic X according to similar calculations, the
Pummerer rearrangement of 11 proceeded selectively at
C5. This can be explained by considering the Saytzeff rule.
Preparation of isomeric pair of 41 were achieved by
modifying Merrer’s protocol.20 Deuterium atoms were
required to be introduced stereoselectively at the C1
position of 1-deoxy-5-thioglucopyranose derivatives for
our purpose (Scheme 4). We designed stereoselective
reduction of the aldehyde 34 for the introduction of the
deuterium atom. The aldehyde 34 was prepared from 33 by
a sequence of the reactions: (i) protection of both terminal
alcohols of 3,4-O-isopropylidene mannitol in forms of the
tert-butyldimethylsilyl (TBDMS) ethers, (ii) mesylation
(iii) partial deprotection of the silyl ether by treatment with
1 equiv. of tetrabutylammonium fluoride (TBAF) in the
presence of acetic acid, and (iv) oxidation with Dess-Martin
reagent.32
The rearrangement must provide the C1–OTFA esters as
the intermediate. However, the TFA ester moieties of them
were converted into C1–alcohols during the work up. This
might proceed by hydrolysis of the ester moiety (retention)
and/or substitution with hydroxyl group at C1 position
(inversion). Further, many of the C1–OH derivatives of
5-thiosugars are under equilibrium between anomers. Thus,
the stereochemistry of the addition of the trifluoroacetate
ion remains unclear. The O-benzoyl group at C2 position of
thiosugars may not induce b-stereoselectivity, so called the
neighboring effect, in this steps based on our experiences,9
It was found that reduction of 34 with sodium borodeuteride
in the presence of cerium (III) chloride in methanol33 took
place stereoselectively, giving alcohol 35 in 91% yield with
(1R)-configuration. The stereoselectivity was estimated to
be 90:10 judging from its 1H NMR spectrum. The
stereochemistry of the newly introduced deuterium was
established at a later stage of the synthesis. The reduction
Table 3. Bond angles /S–C1–C2 and /S–C5–C4 of the model sulfoxides suggested by molecular modeling calculations (6-31Gp)
Model
/S–C1–C2
Sulfide
eq-Oxide
ax-Oxide
112.2
112.1
112.6
107.3
106.5
107.7
115.3
116.3
116.2
/S–C5–C4
Sulfide
eq-Oxide
ax-Oxide
110.9
110.6
111.1
113.9
114.6
114.3
106.3
105.4
106.5

6834
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
was oxidized again under the same conditions as above to
give aldehyde 36. As expected, the reduction with cerium
(III) chloride–sodium borodeuteride in methanol intro-
duced deuterium in the same stereoselectivity (90:10),
giving alcohol 37 in high yield. Then, 37 was converted into
Merrer’s bisepoxide 38 in 67% yield by treatment with
potassium carbonate in methanol at 0 8C. Bisepoxide 38
thus prepared was converted into 1-deoxy-5-thioglucose
derivative 39 according to their report. Treatment of 38 with
sodium sulfide in methanol gave the corresponding
thiepane, which was followed by ring contraction reaction
under the Mitsunobu conditions36 to provide 39 in 72%
yield in two steps. In the same manner as that for 4, the
alcohol function of 39 was converted into benzoate giving
40 in 72% yield. Oxidation of the sulfide group proceeded
smoothly to provide ax-41 and eq-41 in good yields.
The stereochemistries of deuterium-labelled carbons of 41
1
were next determined. The H NMR spectrum of 40 was
quite similar to that of 6 except for the disappearance of two
signals for the C1H (d 2.78 ppm) and one of the C6
methylene protons (d 4.27 ppm) owing to incorporation of
the deuterium atoms37 as shown in Figure 3. The coupling
constant between the remained C1H (2.35 ppm) and C2H
was 9.8 Hz, which suggests that the equatorial proton was
substituted with deuterium. Accordingly, the configuration
at the C1 position was estimated to be (S).
The signal for the remained C6H appeared as a doublet
(J¼3.9 Hz) at 4.82 ppm. Comparing the coupling constant
with that between C5H and C6H in 6 (7.8 Hz) and taking
also the gauche effect38 into account, the stereochemistry at
the C5 position should be (R). This indicates that the
stereochemistries of the primary alcohol moieties of 35 and
37 were both (R)-configuration. Thus, the reduction of both
34 and 36 was presumed to have proceeded through the six-
membered chelation intermediate.39
Scheme 4. Reagents and conditions: (a) (i) TBDMSCl, Et3N, DMF, rt
(100%), (ii) MsCl, Et3N, CH2Cl2, 0 8C (99%), (iii) TBAF, AcOH, THF,
0 8C (67%), (iv) Dess-Martin reagent, CH2Cl2, rt (100%); (b) NaBD4,
CeCl3, MeOH, rt (91%); (c) (i) BzCl, Py, CH2Cl2, rt (90%), (ii) TBAF,
AcOH, THF, rt (98%), (iii) Dess-Martin reagent, CH2Cl2, rt; (d) NaBD4,
CeCl3, MeOH, rt (85% two steps); (e) K2CO3, MeOH, CH2Cl2, 0 8C (67%);
(f) (i) Na2S, DMF, rt (77%), (ii) DEAD, PPh3, benzoic acid, THF, rt (94%);
(g) BzCl, Py, CH2Cl2, rt (72%); (h) mCPBA, CH2Cl2, 0 8C (74%, ax-41/eq-
41¼60:40).
1
The H NMR spectra of the labelled sulfoxides ax-41 and
eq-41 displayed good accordance with those of the non-
labelled ax-10 and eq-10, respectively. These comparisons
of the 1H NMR spectra as well as the Rf values on silica gel
TLC made their stereochemistry incontestable as depicted
in Scheme 4.
with sodium borodeuteride or zinc borodueteride34,35 in
various solvents was found to be ineffective for the
stereoselectivity. Since our synthetic route adopted C2
symmetrical 38 as a key intermediate, deuterium atom had
to be introduced also at another terminal carbon with the
same configuration in order to obtain the labelled substrate
with the deuterium atom at the C1 position (carbohydrate
numbering) in high concentration. Thus, after the TBDMS
group of 35 was removed, the regenerated alcohol moiety
2.5.2. Discussion about the mechanism of the Pummerer
rearrangement based on the results employing ax-41 and
eq-41. The Pummerer rearrangements were examined
employing the labelled substrates ax-41 and eq-41 thus in
hand. As expected, the rearrangement of both ax-41 and
eq-41 took place smoothly by treating with TFAA in the
Figure 3. Part of 1H NMR spectra (2.3–5.6 ppm) of 6 (non-labelled, upper) and 40 (labelled, lower) in C6D6.

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6835
presence of pyridine in CH2Cl2 at room temperature, giving
42 in 56 and 86%, respectively (Scheme 5). The structure of
1
42 was confirmed by comparing the H NMR spectrum to
that of 20. The 1H NMR spectrum suggested that the
deuterium atom was completely retained through the
1
reaction. Interestingly, the H NMR spectrum suggested
that 42 existed as a single isomer, while 20 was observed as
a anomeric mixtures (a/b¼91:9). Since anomers 20 were
under equilibrium on the basis of two-dimensional silica gel
TLC, this might be caused due to isotope effect after
conversion of the corresponding trifluoroacetate into 20.
The signal corresponding to C1H was not detected in the 1H
NMR spectrum of 42. Due to the absence of the C1H signal,
the stereochemistry of the anomeric position could not be
established from the coupling constant. However, the
stereochemistry for the C1 position could be assigned to
be (S)-configuration by taking into account the spectral
profile of other signals in the 1H NMR spectrum as well as
its behavior on silica gel TLC.
Scheme 6.
ion was unclear because of epimerization during and/or after
work up, giving 42.
Since there was only small difference in the yields between
the reaction of the labelled and non-labelled substrates, it is
unlikely that the deuterium atom at the C1 position affected
the reaction process.
However, as regards the reaction mechanism for the
equatorial isomer, our results were different from that
reported by Oae et al. In our experiments, the deuterium
atom at the C1 position was also retained after the
Pummerer reaction of eq-41, which indicates that the bond
between C1 and the axial proton bond was cleaved under the
conditions. In contrast, Oae disclosed that the C2 equatorial
proton of octahydro-2H-thiocromene was removed by E2
1,2-elimination after flipping the thiane ring to the twisted
boat conformation in the case of equatorial sulfoxide. It is
hard to explain the detail of this difference at this stage,
because a complex mixture was obtained when we
attempted the rearrangement of eq-41 under their conditions
(heating with dicyclohexylcarbodiimide, Ac2O). In our case,
the potent leaving ability of the trifluoroacetoxy group might
accelerate the elimination step giving thiocarbenium ion C
at lower temperature and this might give rise to the
difference in the reaction mechanisms (Scheme 6).
Scheme 5. The Pummerer rearrangement of deuterium labelled eq-41 and
ax-41 by TFAA.
As mentioned in Section 2.5.1, we observed a complete
epimerization at the sulfoxide moieties of non-labelled
eq-10 into ax-10 by quenching at the early stage of the
Pummerer reaction. Similar isomerization took place under
the same conditions also in the case of labelled eq-41. Thus,
this isomerization might occur generally under these
conditions. The isomerization of sulfonium ion A to B
may proceed through intermolecular path a or intramole-
cular path b as shown in Scheme 6, although we cannot
figure out at this stage which pathway predominantly
contributes to the isomerization process. Probably, thio-
carbenium ion C might be formed from sulfonium B,
because not even trace amounts of the axial sulfoxides were
detected on the silica gel TLC in the reactions of the
equatorial sulfoxides. The sulfonium ion B seemed to be
hydrolyzed to sulfoxides on the silica gel TLC and also
during the work-up, giving the axial sulfoxides. Inversion of
A by a hydroxy anion can be ruled out because of the
existence of excess TFAA that consumes H2O quickly. In
the process B to C, the possibility of intramolecular
pericyclic deprotonation (path c)40,41 can be eliminated,
because only the C1Hax was lost exclusively (path d) during
the reaction in our experiments. Indeed, the 1H NMR
spectrum of 42 did not display the anomeric proton. These
are consistent with Oae’s report disclosing that the
Pummerer rearrangement of cyclic sulfoxides proceeds
through E2 1,2-elimination.14 As mentioned above, the
stereochemistry of the addition step of the trifluoroacetate
2.6. Synthesis of sulfur substituted isomaltotriose 58 as
an application
Since the sulfur atom, a member of carcogen, is expected to
exhibit similar chemical and physical properties to the
oxygen atom, sulfur-substituted analogues of oligo-
saccharides may be useful inhibitors against the glyco-
sidases.8,42 We applied this rearrangement to a synthesis of
sulfur-substituted isomaltotriose 58 in order to examine its
scope and limitation.
The benzoyl group of ax-9 was removed by sodium
methoxide in methanol. The resulting alcohol 43 was
coupled with thioglucopyranosyl trichloroacetimidate 448
in the presence of a catalytic amount of trimethylsilyl
trifluoromethanesulfonate (TMSOTf)43 in CH2Cl2, giving
the a-glycoside 45 stereoselectively8 in 93% yield
(Scheme 7). Production of the isomer of 45 with
b-glycoside linkage was not detected in this reaction.
Stereochemistry of the newly introduced a-glycoside of 45
was confirmed by observing a small coupling constant
between C10H and C20H (J¼2.5 Hz).

6836
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
Scheme 7. Reagents and conditions: (a) NaOMe, MeOH, rt (100%); (b) 44,
TMSOTf, MS4A, CH2Cl2, 278 8C (93%); (c) TFAA, Py, CH2Cl2, 0 8C!rt
(46: 51%, 47: 26%, 48: 13%); (d) CCl3CN.
On treatment of 45 with TFAA in CH2Cl2 in the presence of
pyridine, the Pummerer rearrangement proceeded to give
alcohol 46 in 51% yield after aqueous work-up. Product 46
was observed as a 72:28 inseparable anomeric mixture.
Stereochemistry of the anomeric position could not be
assigned due to spectral crowding in the 1H NMR spectrum.
Contrary to our expectation, the regioselectivity of the
rearrangement for 45 was a little lower than that in previous
experiments. endo-Olefin 47 and exo-olefin 48 produced
through the rearrangement to the C5 position were isolated
in 26 and 13% yields, respectively. Probably, the bulky
thioglucose moiety attached to the C6 position might affect
the reaction courses of the rearrangement (Scheme 8).
We failed in all attempts to convert the alcohol 46 into
trichloroacetimidate 49 which is required for extension of
the sugar chain. As mentioned in Section 2.4, the acetonide
group of 46 was expected to strain the angle /S–C1–C2 to
be around 1158. This distortion might accelerate the
detachment of the imidate group which might result in the
decomposition of 49 on silica gel. The acetonide group of 46
was removed in order to overcome this problem. Treatment
of the tautomeric mixture of 46 with catalytic hydrochloric
acid in methanol gave an anomeric mixture of triols a-50
and b-50. The 1H NMR spectrum of this mixture indicated
that a-50 was the predominant isomer a-50/b-50¼67:33).
Interestingly, these anomers could be separated by silica gel
column chromatography, although isomers of anomeric
Scheme 8. Reagents and conditions: (a) cat. HCl, MeOH, rt (a-50:61%,
b-50:30%); (b) Ac2O, Py, rt (a-51: 83%, b-51: 89%); (c) H2NNH2–AcOH,
DMF, rt [(a-52: 79%, b-52: 7.8%) from a-51, (a-52: 69%, b-52: 7.0%)
from b-51]; (d) cat. DBU, CCl3CN, CH2Cl2, 0 8C!rt (77%); (e) 54,
TMSOTf, MS4A, CH2Cl2, 278 8C, then separation (a-55: 57%, b-55:
19%); (f) DDQ, CH2Cl2, H2O, rt (a-56: 70%, b-56: 44%, 57: 26%);
(g) (i) NaOMe, MeOH, rt (a-isomer: 79%, b-isomer: 100%), (ii) cat. HCl,
MeOH, rt (a-58: 78%, b-58: 40%).

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6837
alcohols were usually inseparable because of tautomeriza-
tion. Both isomers could be converted to the triacetate
without remarkable isomerization, giving a-51 and b-51
both as almost pure forms in 83 and 89% yields,
respectively. However, on cleavage of the C1 acetyl group
by hydrazine acetate the isomerization resumed. Thus, both
a-51 and b-51 gave a separable mixture of alcohols a-52
and b-52 (91:9 ratio). As expected, a-52 could successfully
be converted into trichloroacetimidate 53 in 77% yield as a
single isomer by treating with trichloroacetonitrile in the
presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU).43
The stereochemistry of 53 was confirmed to be a-
configuration by observing the characteristic coupling
constant (J¼3.4 Hz) for the C1 proton (6.42 ppm).
a-58 and b-58 were purified by medium-pressure ODS
column chromatography.
The 1H NMR spectra of a-58 and its epimer b-58 are shown
in Figure 4. The signal patterns of the anomeric protons of
a-58 revealed that all of the glucosyl bonds of a-58 are
linked by a-configuration, while one of the signals
corresponding to the anomeric protons of b-58 indicates
the existence of b-glycoside linkage. The HSQC and mass
spectra also supported those structures.
3. Conclusion
We have succeeded in developing stereoselective Pummerer
rearrangement reaction of 1-deoxy-5-thio-D-glucopyranose
derivatives carrying an acetonide group at the C3 and C4
positions. Experiments employing deuterium-labelled
derivatives revealed the details of the rearrangement.
Further, this reaction was applied to the preparation of
sulfur-substituted isomaltotriose a-58 and its epimer b-58.
Those carbomimetics are expected to be an effective
antagonist for glycosidases. Enzymatic experiments
employing them are under investigation in our laboratories.
Glycosidation of alcohol 54 with the imidate 53 took place
smoothly by treating with catalytic TMSOTf in the presence
˚
of molecular sieves 4 A, giving adducts a-55 and b-55
(75:25 ratio) in 76% yield. These isomers could be separated
by medium-pressure silica gel column chromatography.
MOM group at the C2 position may partially contribute to
the b-glycosidation. Finally, all protective groups of 55
were removed. Treatment of a-55 with 2,3-dichloro-5,6-
dicyanobenzoquinone (DDQ) smoothly oxidized MPM
ethers.44 These conditions con0s0tructed 4-methoxybenzyl-
idene acetal at the C400 and C6 positions to give a-56 in
70% yield without oxidizing the sulfide moieties.8 The same
oxidation converted b-55 into the benzylidene acetal b-56
in 44% yield along with tetraol 57 (26%). It was found that
the benzylidene moiety of b-56 was gradually cleaved in
CDCl3, affording 57 in quantitative yield. Then, the benzoyl
and acetyl protective groups of both a-56 and 57 were
removed under basic conditions, providing the correspond-
ing nonanols in 79 and 100%, respectively. In the last step,
treatment with catalytic hydrochloric acid in methanol
cleaved the MOM ether and 4-methoxybenzylidene to
provide a-58 in 78%. The same treatment removed the
MOM ether to afford b-58 in 40% yield. The final products
4. Experimental
4.1. General
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 some compounds, con-
sisted of a mixture of diastereomers, the optical rotations
1
were not measured. H NMR spectra were measured on a
JEOL ALPHA 400 spectrometer (400 MHz). The chemical
shifts are expressed in ppm downfield from the signal of
trimethylsilane used as an internal standard in the case of
CDCl3. When another solvent was employed, the remained
proton signals in deuterosolvents C6HD5 (7.15 ppm),
CHD2OD (3.30 ppm), or HDO (4.63 ppm) were used as
the internal standards. Splitting patterns are designated as s
(singlet), d (doublet), t (triplet), m (multiplet), and br
(broad). 13C NMR spectra were recorded also on a JEOL
ALPHA 400 spectrometer (100 MHz). The isotope 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 spectra measured in D2O, default offset was
employed and did not perform correction. Assignments of
the signals are according to the numbering based on IUPAC
nomenclature if not mentioned. For carbohydrate deriva-
tives numbering based on carbohydrate nomenclature is
employed. IR spectra were obtained with a HORIBA
FT-720 Fourier transform infrared spectrometer on a KBr
cell. Measurements of electron impact, field desorption, fast
atom bombardment, and electrospray ionization mass
spectra (EI-MS, FD-MS, FAB-MS, and ESI-MS,
respectively) were performed on a JEOL JMS AX500 or
JEOL JMS AX102A spectrometers in Hokkaido University.
When MS spectra were measured by negative mode,
‘negative mode’ is mentioned. MS analysis for unstable
compounds such as glycosyl imidates was not performed.
Figure 4. 1H NMR spectra (homo decoupling) of isomaltotriose a-58 and
its epimer b-58 in D2O.

6838
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
Analytical and preparative thin-layer chromatographies
were carried out using precoated silica gel plates, Merck
silica gel 60F254 (Art. 1.05715). Silica gel used for column
chromatography was Merck silica gel 60 (Art. 1.07734).
Medium-pressure column chromatographies were per-
formed employing Yamazene ULTRA PACK SI-40B or
Merck Lobarw LiChroprepw RP-18 Type A) equipped with
FMI LAB PUMP RP-SY. All reactions were carried out
under N2 or Ar atmosphere using dried solvents except for
aqueous conditions. Dichloromethane and tetrahydropyran
were freshly distilled from diphosphorus pentoxide and
10.3 Hz, C2H), 7.45–8.06 (10H, aromatic protons), 13C
NMR (CDCl3) d 26.7, 26.8 (C(CH3)2), 30.7 (C1), 44.8 (C5),
63.8 (C6), 73.4 (C2), 78.1 (C4), 80.3 (C3), 109.9 (C(CH3)2),
128.35, 128.41, 129.68, 129.72, 129.72, 129.9, 133.2, 133.3
(aromatic carbons), 165.6, 166.1 (PhCO£2), EI-MS (rel.
int., %) m/z¼413 (6.0, [M2CH3]þ), 306 (2.4, M2
[PhCOOH]þ), 248 (10, [M2PhCOOH–acetone]þ), 105
(100, PhCOþ), FD-MS (rel. int., %) m/z¼428 (63, Mþ), 413
(100, [M2CH3]þ), EI-HRMS; found: m/z 413.1024. Calcd
for C22H21O6S: [M2CH3]þ, 413.1059.
˚
benzophenone-ketyl, respectively. Molecular sieves 4 A
were finely powdered and activated (200 8C in vacuo for
1 h) before use.
4.2. 2,3,4,6-O-Tetrabenzoyl-1,5-dideoxy-5-thio-D-
glucopyranose (7)
4.2.1. Removal of the acetonide. A solution of 4 (224 mg,
690 mmol) in methanol (10 mL) was stirred with concen-
trated aqueous HCl (10 mL) at room temperature for 3 h.
After the mixture was neutralized with Et3N, the mixture
was concentrated in vacuo. Silica gel column chromato-
graphy of the residue (CH2Cl2/acetone¼70:30) gave the
corresponding triol (166 mg, 85%) as a solid. Analytical
sample was obtained by recrystallization from hexane/
EtOAc (50:50) to give colorless needles. mp¼143–144 8C,
[a]2D4¼þ46.5 (c 0.95, MeOH), IR (KBr) 3400, 2920, 1712,
4.1.1. 6-O-Benzoyl-1,5-dideoxy-3,4-O-isopropylidene-2-
O-methoxymethyl-5-thio-D-glucopyranose (5). A mixture
of 6-O-benzoyl-1,5-dideoxy-3,4-O-isopropylidene-5-thio-
D-glucopyranose (4) (317 mg, 978 mmol), prepared accord-
ing to Merrer et al.,20 MOMCl (150 mg, 2.45 mmol), and
iPr2NEt (420 mL, 4.39 mmol) in CH2Cl2 (500 mL) was
stirred at room temperature for 3 h. The mixture was poured
into saturated aqueous NaHCO3 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 chromatography
(hexane/EtOAc¼85:15) gave 5 (311 mg, 86%) as an oil.
[a]2D4¼213.3 (c 1.60, CHCl3), IR (film) d 2985, 2935, 2890,
1725, 1270, 1150, 1105, 1040, 715 cm21, 1H NMR (CDCl3)
d 1.41 (6H, s, C(CH3)2), 2.68 (1H, dd, J¼10.3, 13.2 Hz,
C1HH), 2.92 (1H, dd, J¼4.4, 13.2 Hz, C1HH), 3.34 (1H, t,
J¼10.3 Hz, C3H), 3.38 (3H, s, CH3O), 3.40 (1H, dt, J¼3.9,
8.8 Hz, C5H), 3.66 (1H, dd, J¼8.8, 10.3 Hz, C4H), 3.93
(1H, dt, J¼4.4, 10.3 Hz, C2H), 4.31 (1H, dd, J¼8.8,
11.7 Hz, C6H), 4.73 (1H, d, J¼6.9 Hz, OCHHO), 4.75 (1H,
dd, J¼3.9, 11.7 Hz, C6H), 4.85 (1H, d, J¼6.9 Hz,
OCHHO), 7.43–8.03 (5H, aromatic protons), 13C NMR
(CDCl3) d 26.7, 26.9 (C(CH3)2), 31.9 (C1), 44.6 (C5), 55.5
(CH3O), 63.9 (C6), 77.0 (C2), 77.9 (C4), 82.0 (C3), 96.2
(OCH2O), 109.4 (C(CH3)2), 128.4, 129.7, 129.8, 133.1
(aromatic carbons), 166.0 (PhCO), EI-MS (rel. int., %)
m/z¼353 (7.0, [M2CH3]þ), 306 (7.0, M2[MOMOH]þ),
105 (100, PhCOþ), FD-MS (rel. int., %) m/z¼368 (100,
Mþ), 353 (41, [M2CH3]þ), EI-HRMS; found: m/z
353.1046. Calcd for C17H21O5S: [M2CH3]þ, 353.1059.
1
1275, 1065, 710 cm21, H NMR (CD3OD), d 2.58–2.68
(2H, C1H2), 3.09 (1H, ddd, J¼3.4, 6.4, 10.2 Hz, C5H), 3.14
(1H, t, J¼8.8 Hz, C3H), 3.54 (1H, dd, J¼8.8, 10.2 Hz,
C4H), 3.61 (1H, dt, J¼5.3, 8.8 Hz, C2H), 4.48 (1H, dd,
J¼6.4, 11.7 Hz, C6H), 4.70 (1H, dd, J¼3.4, 11.7 Hz, C6H),
7.47–8.02 (5H, aromatic protons), 13C NMR (CD3OD),
33.4 (C1), 47.3 (C5), 65.1 (C6), 74.8 (C2), 75.4 (C4), 80.7
(C3), 129.6, 130.6, 131.2, 134.3 (aromatic carbons), 167.8
(PhCO), EI-MS (rel. int., %) m/z¼284 (0.2, Mþ), 266 (4.4,
[M2H2O]þ), 248 (3.8, [M22H2O]þ), 162 (68, [M2
PhCOOH]þ), 105 (100, PhCOþ), EI-HRMS; found: m/z
284.0765. Calcd for C13H16O5S: Mþ, 284.0718.
4.2.2. Benzoylation giving 7. A mixture of the product
(166 mg, 584 mmol) and BzCl (340 mL, 2.92 mmol) was
stirred in pyridine (7.0 mL) at room temperature for 24 h.
The mixture was poured into saturated aqueous NaHCO3
and extracted with ether. The combined extracts were
washed with brine, dried over MgSO4, and then concen-
trated in vacuo. Silica gel column chromatography of the
residue (hexane/EtOAc¼85: 15) gave 7 (347 mg, 100%) as
a colorless oil. [a]2D4¼þ31.1 (c 0.88, CHCl3), IR (film)
1
4.1.2. 2,6-O-Dibenzoyl-1,5-dideoxy-3,4-O-isopropyl-
idene-5-thio-D-glucopyranose (6).
1730, 1450, 1270, 1105, 710 cm21, H NMR (CDCl3) d
A
mixture of
4
2.86 (1H, dd, J¼10.8, 13.2 Hz, C1HH), 3.09 (1H, dd,
J¼4.4, 13.2 Hz, C1HH), 3.53 (1H, ddd, J¼3.9, 5.8, 9.7 Hz,
C5H), 4.36 (1H, dd, J¼5.8, 11.7 Hz, C6H), 4.54 (1H, dd,
J¼3.9, 11.7 Hz, C6H), 5.42 (1H, ddd, J¼4.4, 9.7, 10.8 Hz,
C2H), 5.64 (1H, t, J¼9.7 Hz, C3H), 5.76 (1H, t, J¼9.7 Hz,
C4H), 7.10–7.92 (20H, aromatic protons), 13C NMR
(CDCl3) d 30.1 (C1), 44.7 (C5), 62.6 (C6), 73.0 (C4), 73.4
(C2), 74.6 (C3), 128.1, 128.25, 128.33, 128.33, 128.8,
128.9, 129.1, 129.4, 129.5, 129.65, 129.65, 129.72, 133.0,
133.1, 133.2, 133.3 (aromatic carbons), 165.3, 165.4, 165.8,
165.9 (PhCO£4), FD-MS (rel. int., %) m/z¼596 (7.0, Mþ),
595 (13, [M2H]þ), 122 (100, PCOOHþ), FD-HRMS;
found: m/z 596.1485. Calcd for C34H28O8S: Mþ, 596.1505.
(69.4 mg, 214 mmol), BzCl (49.7 mL, 427 mmol), and
pyridine (43.2 mL, 534 mmol) in CH2Cl2 (1.0 mL) was
stirred at room temperature for 20 h. The mixture was
poured into H2O 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 chromatography (hexane/EtOAc¼88:12)
gave 6 (86.9 mg, 95%) as an oil. [a]2D3¼þ81.3 (c 1.18,
CHCl3), IR (film) 2985, 1725, 1270, 1110, 1070, 1025,
1
710 cm21, H NMR (CDCl3) d 1.44, 1.45 (each 3H, s,
C(CH3)2), 2.76 (1H, dd, J¼10.3, 13.7 Hz, C1HH), 3.10 (1H,
dd, J¼4.9, 13.7 Hz, C1HH), 3.49 (1H, ddd, J¼3.5, 7.8,
8.8 Hz, C5H), 3.61 (1H, t, J¼10.3 Hz, C3H), 3.84 (1H, dd,
J¼8.8, 10.3 Hz, C4H), 4.38 (1H, dd, J¼7.8, 11.8 Hz, C6H),
4.81 (1H, dd, J¼3.5, 11.8 Hz, C6H), 5.34 (1H, dt, J¼4.9,
4.2.3. 6-O-Benzoyl-1,5-dideoxy-2,3-O-isopropylidene-5-
thio-D-glucopyranose (8a). A solution of 4 (326 mg,

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6839
1.00 mmol) in acetone (5.0 mL) was stirred with
p-TsOH·H2O (10 mg, 52.6 mmol) at room temperature for
2.5 h. After the mixture was neutralized by the addition of
Et3N, the mixture was concentrated in vacuo. Medium
pressured silica gel column chromatography of the residue
(hexane/EtOAc¼90:10) gave 8a (196 mg, 60%) and
recovered 4(105 mg, 32%) both as oils. The 1HNMRspectrum
of recovered 4 was identical with the authentic sample.
1035, 710 cm21, 1H NMR (C6D6) d 1.14, 1.21 (each 3H, s,
C(CH3)2), 2.69 (1H, ddd, J¼3.0, 4.4, 11.7 Hz, C5H), 2.75
(1H, dd, J¼9.3, 12.2 Hz, C1HH), 3.08 (3H, s, CH3O), 3.19
(1H, dd, J¼9.3, 11.7 Hz, C4H), 3.32 (1H, dd, J¼4.4,
12.2 Hz, C1HH), 3.58 (1H, t, J¼9.3 Hz, C3H), 3.63 (1H, dt,
J¼4.4, 9.3 Hz, C2H), 4.36, 4.64 (each 1H, d, J¼6.8 Hz,
OCH2O), 4.72 (1H, dd, J¼4.4, 12.2 Hz, C6HH), 4.93 (1H,
dd, J¼3.0, 12,2 Hz, C6HH), 7.03–7.12 (3H, aromatic
protons), 8.17–8.19 (2H, aromatic protons), 13C NMR
(C6D6) d 26.71, 26.74 (C(CH3)2), 55.2 (CH3O), 55.4 (C1),
59.6 (C6), 64.2 (C5), 69.2 (C2), 71.0 (C4), 82.4 (C3), 95.6
(OCH2O), 111.7 (C(CH3)2), 128.6, 130.0, 130.5, 133.1
(aromatic carbons), 165.7 (PhCO), EI-MS (rel. int., %)
m/z¼385 (trace, MþHþ), 369 (5.7, [M2CH3]þ), 322 (1.0
[M2MOMOH]þ), 105 (100, PhCOþ), FD-MS (rel. int., %)
m/z¼385 (18, [MþH]þ), 369 (100, [M2CH3]þ), EI-HRMS;
found: m/z 369.0986. Calcd for C17H21O7S: [M2CH3]þ,
369.1008.
4.2.4. Physical data for 8a. [a]2D1¼þ55.8 (c 0.90, CHCl3),
IR (film) 2985, 2920, 1720, 1270, 1115, 715 cm21, 1H NMR
(C6D6) d 1.32, 1.33 (each 3H, s, C(CH3)2), 2.43 (2H, C1H2),
2.88 (1H, dt, J¼4.4, 9.2 Hz, C5H), 3.05 (1H, t, J¼9.2 Hz,
C4H), 3.66 (1H, dt, J¼6.8, 9.2 Hz, C2H), 3.75 (1H, t,
J¼9.2 Hz, C3H), 4.65 (2H, d, J¼4.4 Hz, C6H2), 7.02–8.16
(5H, aromatic protons), 13C NMR (C6D6) d 26.9, 27.0
(C(CH3)2), 30.6 (C1), 47.0 (C5), 63.1 (C6), 72.6 (C4), 77.1
(C2), 84.2 (C3), 109.6 (C(CH3)2), 128.5, 128.6, 130.1,
130.4, 133.1 (aromatic carbons), 166.4 (PhCO), EI-MS (rel.
int., %), 309(3.5, [M2CH3]þ), 267 (1.4, [M2isobutene]þ),
105 (51, PhCOþ), EI-HRMS; found: m/z 309.0788. Calcd
for C15H17O5S: [M2CH3]þ, 309.0797.
4.3.3. Physical data for ax-9. [a]2D3¼þ15.1 (c 0.98,
CHCl3), IR (film) 2985, 2935, 2895, 1725, 1270, 1235,
1150, 1105, 1060, 1035, 715 cm21, 1H NMR (C6D6) d 1.21,
1.30 (each 3H, s, C(CH3)2), 1.69 (1H, dd, J¼11.2, 14.6 Hz,
C1HH), 2.53 (1H, dt, J¼4.4, 11.7 Hz, C5H), 3.10 (3H, s,
CH3O), 3.20 (1H, dd, J¼4.4, 14.6 Hz, C1HH), 3.29 (1H, t,
J¼9.3 Hz, C3H), 4.25 (1H, dd, J¼9.3, 11.7 Hz, C4H), 4.45
(1H, d, J¼6.4 Hz, OCHHO), 4.62 (1H, ddd, J¼4.4, 9.3,
11.2 Hz, C2H), 4.68 (1H, dd, J¼10.8, 11.7 Hz, C6HH), 4.74
(1H, d, J¼6.4 Hz, OCHHO), 5.14 (1H, dd, J¼4.4, 10.8 Hz,
C6HH), 7.03–7.13 (3H, aromatic protons), 8.15–8.17 (2H,
aromatic protons), 13C NMR (C6D6) d 26.6, 26.9 (C(CH3)2),
50.6 (C1), 55.2 (CH3O), 58.8 (C5), 59.9 (C6), 71.1 (C2),
72.7 (C4), 82.3 (C3), 96.1 (OCH2O), 109.9 (C(CH3)2),
128.5, 128.6, 130.1, 130.3, 133.2 (aromatic carbons), 165.8
(PhCO), EI-MS (rel. int., %) m/z¼369 (4.0, [M2CH3]þ),
262 (13, [M2PhCOOH]þ), 105 (100, PhCOþ), FD-MS (rel.
int., %) m/z¼384 (31, Mþ), 369 (100, [M2CH3]þ), EI-
HRMS; found: m/z 369.1024. Calcd for C17H21O7S:
[M2CH3]þ, 369.1008.
4.2.5. 4-Acetoxy-6-O-benzoyl-1,5-dideoxy-2,3-O-iso-
propylidene-5-thio-D-glucopyranose (8b). A solution of
8a (340 mg, 1.05 mmol) in a mixture of Ac2O (3.0 mL) and
pyridine (6.0 mL) was stirred at room temperature for 1.5 h.
After concentration, silica gel column chromatography of
the residue (hexane/EtOAc¼80:20) gave 8b (384 mg,
100%) as a colorless oil. [a]2D1¼þ51.8 (c 6.2, CHCl3), IR
1
(film) 2985, 1725, 1375, 1240, 1115, 1025, 715 cm21, H
NMR (C6D6) d 1.26, 1.29 (each 3H, s, C(CH3)2), 1.64 (3H,
s, CH3CO), 2.37 (2H, C1H2), 2.98 (1H, ddd, J¼3.4, 6.3,
9.7 Hz, C5H), 3.17 (1H, dd, J¼8.8, 9.7 Hz, C3H), 3.75 (1H,
dt, J¼7.3, 8.8 Hz, C2H), 4.30 (1H, dd, J¼6.3, 12.2 Hz,
C6HH), 4.58 (1H, dd, J¼3.4, 12.2 Hz, C6HH), 5.55 (1H, t,
J¼9.7 Hz, C4H), 7.05–8.23 (5H, aromatic protons), 13C
NMR (C6D6) 20.3 (CH3CO), 26.87, 26.88 (C(CH3)2), 30.5
(C1), 45.2 (C5), 62.4 (C6), 72.6 (C4), 77.5 (C2), 81.9 (C3),
109.9 (C(CH3)2), 128.5, 128.6, 130.1, 130.4, 133.1 (aromatic
carbons), 165.9, 169.2 (PhCO£2), EI-MS (rel. int., %)
m/z¼351 (3.7, [M2CH3]þ), 306 (0.7, [M2AcOH]þ), 184
(34, [M2AcOH–PhCOOH]þ), 126 (57, [M2AcOH–
PhCOOH–acetone]þ), 105 (100, PhCOþ), EI-HRMS;
found: m/z 351.0902. Calcd for C17H19O6S: [M2CH3]þ,
351.0902.
4.4. 2,6-O-Dibenzoyl-1,5-dideoxy-3,4-O-isopropylidene-
5-thio-D-glucopyranose (R)-S-oxide (eq-10) and its (S)-
isomer (ax-10)
Treatment of 6 (25.0 mg, 58.3 mmol) in a similar manner as
described in Section 4.3.1 gave eq-10 (14.1 mg, 55%) ax-10
(9.5 mg, 36.7%) after silica gel column chromatography
(benzene/EtOAc¼95:5).
4.3. 6-O-Benzoyl-1,5-dideoxy-3,4-O-isopropylidene-2-O-
methoxymethyl-5-thio-D-glucopyranose (R)-S-oxide (eq-
9) and its (S)-isomer (ax-9)
4.4.1. Physical data for eq-10. [a]2D4¼þ41.9 (c 0.80,
CHCl3), IR (film) 3445, 2985, 1725, 1270, 1265, 1105,
1045, 705 cm21, 1H NMR (C6D6) d 1.13, 1.22 (each 3H, s,
C(CH3)2), 2.66 (1H, dd, J¼9.3, 12.7 Hz, C1HH), 2.82 (1H,
ddd, J¼3.4, 5.4, 11.2 Hz, C5H), 3.24 (1H, dd, J¼4.9,
12.7 Hz, C1HH), 3.25 (1H, dd, J¼9.3, 11.2 Hz, C4H), 3.99
(1H, t, J¼9.3 Hz, C3H), 4.62 (1H, dd, J¼5.4, 12.2 Hz,
C6HH), 4.82 (1H, dd, J¼3.4, 12.2 Hz, C6HH), 5.32 (1H, dt,
J¼4.9, 9.3 Hz, C2H), 6.98–8.16 (10H, aromatic protons),
13C NMR (C6D6) d 26.6, 26.8 (C(CH3)2), 53.4 (C1), 60.0
(C6), 64.8 (C5), 67.8 (C2), 71.4 (C4), 79.8 (C3), 112.1
(C(CH3)2), 128.55, 128.60, 129.9, 130.0, 130.1, 130.3,
133.2, 133.4 (aromatic carbons), 165.2, 166.7 (PhCO£2),
EI-MS (rel. int., %) m/z¼445 (0.3, [MþH]þ), 429 (0.8,
4.3.1. Preparation. A mixture of 5 (658 mg, 1.79 mmol)
and mCPBA (70% purity, 439 mg, 1.79 mmol) was stirred
in CH2Cl2 (5.0 mL) at 220 8C for 30 min. The mixture was
poured into 5% aqueous sodium thiosulfate solution and
extracted with CH2Cl2. The combined extracts were washed
with brine, dried over MgSO4, and then concentrated in
vacuo. Silica gel column chromatography of the
residue (benzene/EtOAc¼70:30) gave eq-9 (302 mg, 44%)
and ax-9 (298 mg, 43%) both as colorless oils.
4.3.2. Physical data for eq-9. [a]2D3¼245.3 (c 1.35,
CHCl3), (film) 2980, 2925, 1725, 1270, 1150, 1105, 1050,

6840
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
[M2CH3]þ), 264 (0.6, [M2PhCOOH–acetone]þ), 105
(100, PhCOþ), EI-HRMS; found m/z 445.1291. Calcd for
C23H25O7S: [MþH]þ, 445.1321.
4.6. 4-Acetoxy-6-O-benzoyl-1,5-dideoxy-2,3-O-
isopropylidene-5-thio-D-glucopyranose (R)-S-oxide
(eq-12) and its (S)-isomer (ax-12)
4.4.2. Physical data for ax-10. [a]2D4¼þ46.1 (c 0.92,
,
710 cm21 1H NMR (C6D6) d 1.15, 1.30 (each 3H, s,
Treatment of 8b (74.4 mg, 203 mmol) in a similar manner as
described in Section 4.3.1 gave eq-12 (42.6 mg, 55%) and
ax-12 (28.7 mg, 37%) after silica gel column chromato-
graphy (benzene/EtOAc¼80:20). Analytical sample for
ax-12 was obtained by recrystallization from hexane/
EtOAc (50:50) giving plates.
CHCl3), IR (film) 3735, 2920, 2850, 1720, 1270, 1105,
C(CH3)2), 1.58 (1H, dd, J¼10.7, 14.1 Hz, C1HH), 2.65 (1H,
dt, J¼4.4, 11.2 Hz, C5H), 3.33 (1H, dd, J¼3.9, 14.1 Hz,
C1HH), 3.48 (1H, dd, J¼9.8, 10.7 Hz, C3H), 4.39 (1H, dd,
J¼9.8, 11.2 Hz, C4H), 4.68 (1H, d, J¼11.2, 12.7 Hz,
C6HH), 5.16 (1H, dd, J¼4.4, 12.7 Hz, C6HH), 6.13 (1H, dt,
J¼3.9, 10.7 Hz, C2H), 6.99–8.16 (10H, aromatic protons),
13C NMR (C6D6) d 26.4, 27.0 (C(CH3)2), 49.2 (C1), 59.2
(C5), 59.9 (C6), 69.3 (C2), 72.9 (C4), 80.3 (C3), 110.5
(C(CH3)2), 128.5, 128.7, 130.0, 130.0, 130.1, 130.2, 133.2,
133.3 (aromatic carbons), 165.0, 165.8 (PhCO£2), EI-MS
(rel. int., %) m/z¼444 (0.7, Mþ), 429 (1.0, [M2CH3]þ),
322 (1.8, [M2PhCOOH]þ), 264 (5.5, [M2PhCOOH–
acetone]þ), 105 (100, PhCOþ), EI-HRMS; found: m/z
444.1214. Calcd for C23H24O7S: Mþ, 444.1243.
4.6.1. Physical data for eq-12. [a]2D1¼216.2 (c 0.39,
CHCl3), IR (film) 2985, 1730, 1375, 1240, 1100, 1025,
710 cm21 1H NMR (C6D6) d 1.12, 1.21 (each 3H, s,
,
C(CH3)2), 1.51 (3H, s, CH3CO), 2.55 (1H, dd, J¼10.7,
13.2 Hz, C1HH), 2.73 (1H, ddd, J¼3.0, 4.8, 11.2 Hz, C5H),
3.05 (1H, ddd, J¼2.4, 9.3, 13.2 Hz, C2H), 3.28 (1H, dd,
J¼2.4, 10.7 Hz, C1HH), 3.44 (1H, t, J¼9.3 Hz, C3H), 4.68
(1H, dd, J¼3.0, 12.7 Hz, C6HH), 4.93 (1H, dd, J¼4.8,
12.7 Hz, C6HH), 5.50 (1H, dd, J¼9.3, 11.2 Hz, C4H),
7.03–8.21 (5H, aromatic protons), 13C NMR (C6D6) d 20.1
(CH3CO), 26.5, 26.7 (C(CH3)2), 52.2 (C1), 56.5 (C6), 65.0
(C4), 67.0 (C5), 69.1 (C2), 81.6 (C5), 111.8 (C(CH3)2),
127.9, 128.6, 130.1, 133.2 (aromatic carbons), 165.8, 168.6
(CH3CO and PhCO), EI-MS (rel. int., %) m/z¼383 (0.4,
[MþH]þ), 367 (1.5, [M2CH3]þ), 322 (1.2, [M2AcOH]þ),
105 (100, PhCOþ), EI-HRMS; found: m/z 383.1168. Calcd
for C18H23O7S: Mþ, 383.1164.
4.5. 2,3,4,6-O-Tetrabenzoyl-1,5-dideoxy-5-thio-D-gluco-
pyranose (R)-S-oxide (eq-11) and its (S)-isomer (ax-11)
Treatment of 7 (347 mg, 581 mmol) in a similar manner
as described in Section 4.3.1 gave eq-11 (170 mg, 48%)
and ax-11 (172 mg, 48%) after silica gel column
chromatography (benzene/EtOAc¼90: 10).
4.6.2. Physical data for ax-12. Mp¼181–182 8C,
[a]2D1¼þ142 (c 1.78, CHCl3), IR (KBr) 2985, 1730, 1375,
1240, 1100, 1050, 715 cm21, 1H NMR (C6D6) d 1.18, 1.29
(each 3H, s, C(CH3)2), 1.63 (1H, dd, J¼12.2, 13.2 Hz,
C1HH), 1.65 (3H, s, CH3CO), 2.52 (1H, dt, J¼3.9, 9.8 Hz,
C5H), 3.03 (1H, dd, J¼3.4, 13.2 Hz, C1HH), 3.30 (1H, t,
J¼9.8 Hz, C3H), 4.61 (1H, ddd, J¼3.4, 9.8, 12.2 Hz, C2H),
4.68 (1H, dd, J¼9.8, 11.7 Hz, C6HH), 4.86 (1H, dd, J¼3.9,
11.7 Hz, C6HH), 6.00 (1H, t, J¼9.8 Hz, C4H), 7.04–8.16
(5H, aromatic protons), 13C NMR (C6D6) d 20.2 (CH3CO),
26.5, 27.0 (C(CH3)2), 48.1 (C1), 59.8 (C6), 60.6 (C5), 68.9
(C4), 71.6 (C2), 81.1 (C3), 110.6 (C(CH3)2), 128.7, 130.05,
130.11, 133.4 (aromatic carbons), 165.9, 169.2 (CH3CO and
PhCO), EI-MS (rel. int., %) m/z¼383 (2.1, [MþH]þ), 367
(0.7, [M2CH3]þ), 105 (100, PhCOþ), EI-HRMS; found:
m/z 383.1208. Calcd for C18H23O7S: [MþH]þ, 383.1164.
4.5.1. Physical data for eq-11. [a]2D4¼þ45.2 (c 0.80,
1
CHCl3), IR (film) 1730, 1265, 1105, 710 cm21, H NMR
(CDCl3) d 3.22 (1H, t, J¼11.8 Hz, C1HH), 3.49 (1H, dt,
J¼2.5, 11.7 Hz, C5H), 4.02 (1H, dd, J¼3.9, 11.8 Hz,
C1HH), 4.68 (1H, dd, J¼2.5, 12.7 Hz, C6HH), 4.86 (1H, dd,
J¼2.5, 12.7 Hz, C6HH), 5.45 (1H, ddd, J¼3.9, 9.8, 11.8 Hz,
C2H), 5.79 (1H, dd, J¼9.8, 11.7 Hz, C4H), 5.90 (1H, t,
J¼9.8 Hz, C3H), 7.10–7.5 (20H, aromatic protons),
13C NMR (CDCl3) d 52.6 (C1), 56.6 (C6), 64.8 (C4), 65.3
(C2), 65.7 (C5), 74.0 (C3), 128.1, 128.2, 128.27, 128.32,
128.36, 128.39, 128.44, 128.5, 129.6, 129.7, 129.8, 129.8,
133.3, 133.4, 133.6, 133.7 (aromatic carbons), 164.7, 165.1,
165.5, 165.6 (PhCO£4), EI-MS (rel. int., %) m/z¼612
(0.6, Mþ), 490 (3.3, [M2PhCOOH]þ), 105 (100, PhCOþ),
EI-HRMS; found: m/z 612.1484. Calcd for C34H28O9S: Mþ,
612.1454.
4.7. Pummerer rearrangement of 1,5-dideoxy-5-thio-D-
glucopyranose derivatives
4.5.2. Physical data for ax-11. [a]2D3¼þ12.8 (c 1.0,
1
CHCl3), IR (film) 1730, 1270, 1105, 710 cm21, H NMR
(CDCl3) d 2.72 (1H, dd, J¼11.7, 14.2 Hz, C1HH), 3.38 (1H,
ddd, J¼4.9, 9.3, 11.2 Hz, C5H), 3.85 (1H, dd, J¼3.9,
14.2 Hz, C1HH), 4.64 (1H, dd, J¼9.3, 12.2 Hz, C6HH),
4.78 (1H, dd, J¼4.9, 12.2 Hz, C6HH), 5.90 (1H, t,
J¼9.8 Hz, C3H), 6.10 (1H, ddd, J¼3.9, 9.8, 11.7 Hz,
C2H), 6.23 (1H, dd, J¼9.8, 11.2 Hz, C4H), 7.11–7.88
(20H, aromatic protons), 13C NMR (CDCl3) d 47.4 (C1),
59.0 (C5), 60.0 (C6), 67.3 (C2), 67.9 (C4), 73.8 (C3), 128.2,
128.3, 128.38, 128.38, 128.42, 128.5, 128.8, 129.0, 129.6,
129.7, 129.76, 129.80, 133.3, 133.41, 133.43, 133.5
(aromatic carbons), 164.9, 165.2, 165.8, 165.9 (PhCO£4),
EI-MS (rel. int., %) m/z¼612 (3.1, Mþ), 490 (1.4, [M2
PhCOOH]þ), 105 (100, PhCOþ), EI-HRMS; found: m/z
612.1484. Calcd for C34H28O9S: Mþ, 612.1454.
4.7.1. Typical conditions. To a mixture of sulfoxide and
pyridine (10 equiv.) in CH2Cl2, TFAA (5 equiv.) was added
at 0 8C. After 5 min, the cooling bath was removed and the
mixture was stirred at room temperature until TLC indicated
that the starting sulfoxide was disappeared. After addition of
MeOH to decompose excess TFAA, the mixture was poured
into H2O and extracted with EtOAc. The combined extracts
were washed with brine, dried over MgSO4, and then
concentrated in vacuo. Silica gel column chromatography of
the residue gave products.
4.7.2. Reaction of eq-9 (run 1). Treatment of eq-9
(15.0 mg, 39.3 mmol) in a similar manner as described in
Section 4.7.1 gave 15 (14 mg) as an oil after silica gel

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6841
column chromatography (benzene/EtOAc¼90: 10). Since
15 was observed as broad spot on silica gel TLC, accurate
yield of 15 could not be obtained. Analytical sample was
prepared from a part of the fractions. The yield of this
reaction was estimated to be 66% after acetylation of the
alcohol moiety as described in Section 4.12. Physical data
for 15 are follows; [a]D23¼þ32.9 (c 1.56, CHCl3), IR (film)
3440, 2930, 1725, 1275, 1235, 1155, 1106, 1070, 1030,
(a-isomer)), 4.78 (1H£a, dd, J¼3.9, 11.7 Hz, C6HH
(a-isomer)), 5.11 (1H£a, br, C1H (a-isomer)), 5.54
(1H£a, dd, J¼2.9, 10.7 Hz, C2H (a-isomer)), 5.65 (1H£b,
dd, J¼8.0, 10.3 Hz, C2H (b-isomer)), 6.96–7.15 (6H,
aromatic protons), 8.16–8.20 (4H, aromatic protons), 13C
NMR (C6D6, signals for only major isomer are described.) d
26.7, 27.0 (C(CH3)2), 42.2 (C5), 63.6 (C6), 74.1 (C1), 75.8
(C3), 76.5 (C2), 79.2 (C4), 109.9 (C(CH3)2), 128.46,
128.54, 130.1, 130.2, 130.3, 130.4, 133.1, 133.2 (aromatic
carbons), 165.91, 169.94 (PhCO£2), EI-MS (rel. int., %)
m/z¼445 (0.8, MHþ), 429 (1.8, [M2CH3]þ), 369 (1.2,
[M2acetone–OH]þ), 322 (4.5, [M2PhCOOH]þ), 105
(100, PhCOþ), FD-MS m/z¼445 (76, MHþ), 429 (100,
[M2CH3]þ), EI-HRMS; found: m/z 429.1012. Calcd for
C22H21O7S: [M2CH3]þ, 429.1008.
1
715 cm21. The H NMR spectrum of this sample showed
that it consists of the two tautomers arising from the C1
anomeric position (a-anomer/b-anomer¼90:10). Assign-
ments of the signals for the main isomer and some for the
minor isomer are described. 1H NMR (C6D6, a¼0.9, b¼0.1)
d 1.27, 1.29 (each 3H£a, s, C(CH3)2 (a-isomer)), 3.11
(3H£a, s, CH3O (a-isomer)), 3.16 (3H£b, s, CH3O
(b-isomer)), 3.46 (1H£b, t, J¼9.3 Hz, C4H (b-isomer)),
3.65 (1H£a, ddd, J¼2.9, 6.8, 10.8 Hz, C5H (a-isomer)),
3.71 (1H£a, dd, J¼8.3, 10.8 Hz, C4H (a-isomer)), 3.92
(1H£a, dd, J¼3.0, 10.3 Hz, C2H (a-isomer)), 4.07 (1H£a,
dd, J¼8.3, 10.3 Hz, C3H (a-isomer)), 4.35 (1H£b, dd,
J¼7.3, 11.2 Hz, C6HH (b-isomer)), 4.41 (1H£a, dd, J¼7.3,
11.7 Hz, C6HH (a-isomer)), 4.47 (1H£a, d, J¼6.8 Hz,
OCHHO (a-isomer)), 4.63 (1H£b, d, J¼6.4 Hz, OCHHO
(b-isomer)), 4.70 (1H£a, d, J¼6.8 Hz, OCHHO
(a-isomer)), 4.74 (1H£b, d, J¼6.4 Hz, OCHHO
(b-isomer)), 4.78 (1H£a, dd, J¼2.9, 11.7 Hz, C6HH
(a-isomer)), 4.80 (1H£a, d, J¼3.0 Hz, C1H (a-isomer)),
7.00–7.05 (3H, aromatic protons), 8.17 (2H, aromatic
protons), 13C NMR (C6D6, signals for only major isomer are
described.) d 26.7, 27.1 (C(CH3)2), 42.2 (C5), 55.3 (CH3O),
63.7 (C6), 75.0 (C1), 77.5 (C3), 78.9 (C4), 79.5 (C2), 95.9
(OCH2O), 109.4 (C(CH3)2), 128.5, 130.1, 130.5, 133.0
(aromatic carbons), 165.9 (PhCO), FD-MS (rel. int., %)
m/z¼384 (75, Mþ), 369 (100, [M2CH3]þ), FD-HRMS;
found: m/z 384.1261. Calcd for C18H24O7S: Mþ,
384.1243.
4.8. Reaction of ax-10 in CH2Cl2 (run 4)
Treatment of ax-10 (45.0 mg, 101 mmol) in a similar
manner as described in Section 4.7.1 gave 20 (22.3 mg,
55%) and trace amount of 21, 22, and 23 after column
chromatography. The 1H NMR spectrum of 20 was identical
with that prepared from eq-10.
4.9. Reaction of eq-10 in pyridine (run 5)
Treatment of eq-10 (40.5 mg, 91.2 mmol) with TFAA
(30 mL, 212 mmol) in pyridine (1.5 mL) in a similar manner
as described in Section 4.7.1 gave 20 (26.5 mg, 66%) after
column chromatography. The 1H NMR spectrum of 20 was
identical with that reported in Section 4.7.4.
4.10. Reaction of ax-10 in pyridine (run 6)
Treatment of ax-10 (60.1 mg, 135 mmol) in a similar
manner as described in Section 4.7.1 gave 20 (39.7 mg,
65%) after column chromatography. The 1H NMR spectrum
of 20 was identical with that reported in Section 4.7.5.
4.7.3. Reaction of ax-9 (run 2). Treatment of ax-9
(46.6 mg, 121 mmol) in a similar manner as described in
Section 4.7.1 gave 15 (60 mg), and trace amount of 19. The
yield of 15 was estimated to be 84% after acetylation. The
1H NMR spectrum of 15 was identical with that prepared
from eq-9.
4.11. Reaction of eq-11 (run 7)
Treatment of eq-11 (74 mg, 121 mmol) in a similar manner
as described in Section 4.7.1 gave 24 (4.2 mg, 5.7%), 25
(4.8 mg, 4.0%), 26 (37.0 mg, 50%), 27 (5.6 mg, 8.9%), and
28 (11.5 mg, 8.9%) after column chromatography. The
structure of 27 was estimated from the results that
treatment of 27 with Et3N in MeOH at room temperature
produced 26.
4.7.4. Reaction of eq-10 in CH2Cl2 (run 3). Treatment of
eq-10 (30.1 mg, 67.7 mmol) in a similar manner as
described in Section 4.7.1 gave 20 (22.3 mg, 55%) and
trace amount of 21, 22, and 23 after column chromato-
graphy (hexane/EtOAc¼80:20).
4.11.1. Physical data for a-24. [a]2D2¼þ90.3 (c 0.56,
1
4.7.5. Physical data for 20. [a]2D4¼þ99.9 (c 3.02, CHCl3),
CHCl3), IR (film) 3450, 1730, 1270, 1105, 710 cm21, H
IR (film) 3440, 2985, 2980, 1720, 1270, 1110, 1070,
NMR (CDCl3), d 2.51 (1H, d, J¼2.0 Hz, OH), 4.00 (1H,
ddd, J¼3.9, 4.8, 10.7 Hz, C5H), 4.42 (1H, dd, J¼4.8,
11.7 Hz, C6HH), 4.50 (1H, dd, J¼3.9, 11.7 Hz, C6HH),
5.35 (1H, dd, J¼2.0, 2.9 Hz, C1H), 5.49 (1H, dd, J¼2.9,
10.3 Hz, C2H), 5.82 (1H, t, J¼10.7 Hz, C4H), 6.13 (1H, dd,
J¼10.3, 10.7 Hz, C3H), 7.08–7.45 (12H, aromatic protons),
7.66–7.92 (8H, aromatic protons), 13C NMR (CDCl3) d
39.5 (C5), 62.2 (C6), 70.8 (C3), 71.9 (C1), 73.1(C4), 75.9
(C2), 128.18, 128.23, 128.3, 128.40, 128.42, 128.9, 129.0,
129.4, 129.5, 129.8, 129.81, 129.84, 133.0, 133.2, 133.3,
133.4 (aromatic carbons), 165.4, 165.7, 165.8, 166.0
(PhCO£4), FD-MS (rel. int., %) m/z¼612 (19, Mþ), 611
1
710 cm21. The H NMR spectrum of this sample showed
that it consists of the two tautomers arising from the C1
anomeric position (a-anomer/b-anomer¼91:9). Assign-
ments of the signals for the main isomer and some for the
minor isomer are described. 1H NMR (C6D6, a¼0.9, b¼0.1)
d 1.28, 1.30 (each 3H£a, s, C(CH3)2 (a-isomer)), 1.24, 1.25
(each 3H£b, s, C(CH3)2 (b-isomer)), 3.66 (1H£a, ddd,
J¼3.9, 7.8, 11.2 Hz, C5H (a-isomer)), 3.82 (1H£a, dd,
J¼8.8, 10.8 Hz, C4H (a-isomer)), 4.08 (1H£b, t, J¼8.0 Hz,
C4H (b-isomer)), 4.38 (1H£a, dd, J¼7.3, 11.7 Hz, C6HH
(a-isomer)), 4.40 (1H£a, dd, J¼8.8, 10.8 Hz, C3H

6842
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
(34, [M2H]þ), 491 (36, [MH2PhCOOH]þ), 122 (99,
PhCOOHþ), 105 (100, PhCOþ), FD-HRMS; found: m/z
612.1470. Calcd for C34H28O9S: Mþ, 612.1454.
129.5, 129.8, 129.9, 129.93, 132.96, 133.3, 133.4, 133.6
(aromatic carbons), 165.61, 165.65, 165.8, 166.9
(PhCO£4), FD-MS (rel. int., %) m/z¼612 (100, Mþ), 595
(19, [M2OH]þ), FD-HRMS; found: m/z 612.1478. Calcd
for C34H28O9S: Mþ, 612.1454.
4.11.2. Physical data for b-24. [a]2D2¼þ36.4 (c 0.44,
1
CHCl3), IR (film) 3440, 1730, 1270, 1105, 710 cm21, H
NMR (CDCl3), d 3.20 (1H, d, J¼8.3 Hz, OH), 3.67 (1H,
ddd, J¼4.4, 5.9, 10.7 Hz, C5H), 4.49 (1H, dd, J¼5.9,
11.7 Hz, C6HH), 4.63 (1H, dd, J¼4.4, 11.7 Hz, C6HH),
5.18 (1H, t, J¼8.3 Hz, C1H), 5.64 (1H, t, J¼8.3 Hz, C2H),
5.77 (1H, dd, J¼8.3, 10.7 Hz, C3H), 5.87 (1H, t, J¼10.7 Hz,
C4H), 7.15–7.55 (12H, aromatic protons), 7.75–8.05 (8H,
aromatic protons), 13C NMR (CDCl3) d 41.9 (C5), 62.5
(C6), 72.62 (C3), 72.67 (C4), 74.9 (C1), 77.5 (C2), 128.2,
128.35, 128.41, 128.43, 128.65, 128.69, 128.7, 129.3, 129.6,
129.75, 129.81, 129.9, 133.24, 133.24, 133.4, 133.7
(aromatic carbons), 165.3, 165.7, 166.0, 167.3 (PhCO£4),
FD-MS (rel. int., %) m/z¼612 (20, Mþ), 611 (31, [M2H]þ),
491 (25, [MH2PhCOOH]þ), 122 (56, PhCOOHþ), 105
(100, PhCOþ), FD-HRMS; found: m/z 612.1429. Calcd for
C34H28O9S: Mþ, 612.1454.
4.11.6. Reaction of ax-11 (run 8). Treatment of eq-11
(106 mg, 173 mmol) in a similar manner as described in
Section 4.7.1 gave 24 (2.8 mg, 2.7%), 25 (0.3 mg, 0.3%), 26
(43.5 mg, 41%), 27 (5.6 mg, 5.6%), and 28 (9.1 mg, 8.1%)
after column chromatography.
4.11.7. Reaction of eq-12 (run 9). Treatment of eq-12
(52.2 mg, 136 mmol) in a similar manner as described
in Section 4.7.1 gave 30 (6.9 mg, 14%), 31 (20.9 mg,
40%) and 32 (1.1 mg, 1.7%), after column chromatography.
The structure of 32 was estimated by production of 30
and 31 by treating 32 with Et3N in MeOH at room
temperature.
4.11.8. Physical data for 30. [a]2D2¼2159.2 (c 0.68,
CHCl3), IR (film) 3450, 2985, 2935, 1740, 1225, 1135,
1080, 1045, 705 cm21, 1H NMR (C6D6) d 1.27, 1.29 (each
3H, s, C(CH3)2), 1.64 (3H, s, CH3CO), 2.45 (2H, C1H2),
3.40 (1H, dd, J¼8.8, 10.2 Hz, C3H), 3.78 (1H, dt, J¼5.8,
8.8 Hz, C2H), 6.05 (1H, dd, J¼2.0, 10.2 Hz, C4H), 6.99–
8.19 (5H, aromatic protons), 7.93 (1H, d, J¼2.0 Hz,
C6H), 13C NMR (C6D6) d 20.1 (CH3CO), 26.8, 26.9
(C(CH3)2), 31.7 (C1), 72.8 (C4), 76.6 (C2), 81.1 (C3), 109.9
(C(CH3)2), 114.8 (C5), 128.7, 130.5, 133.8, 134.9
(aromatic carbons), 162.7, 169.0 (CH3CO and PhCO),
EI-MS (rel. int., %) m/z¼364 (0.5, Mþ), 349 (0.5,
[M2CH3]þ), 289 (1.3, [M2acetone–OH]þ), 105 (100,
PhCOþ), EI-HRMS; found: m/z 364.0972. Calcd for
C18H20O6S: Mþ, 364.0981.
4.11.3. Physical data for 25. [a]2D2¼266.3 (c 0.41, CHCl3),
IR (film) 1730, 1260, 1095, 710 cm21, 1H NMR (CDCl3), d
2.98 (1H, dd, J¼9.8, 12.7 Hz, C1HH), 3.14 (1H, dd, J¼4.4,
12.7 Hz, C1HH), 5.50 (1H, ddd, J¼4.4, 7.8, 9.8 Hz, C2H),
5.63 (1H, t, J¼7.8 Hz, C3H), 6.03 (1H, dd, J¼1.5, 7.8 Hz,
C4H), 7.20–7.53 (12H, aromatic protons), 7.76 (1H, d,
J¼1.5 Hz, C6H), 7.77–8.04 (8H, aromatic protons), 13C
NMR (CDCl3) d 29.9 (C1), 71.6 (C4), 72.2 (C2), 73.7 (C3),
112.9 (C5), 128.33, 128.35, 128.4, 128.5, 128.7, 128.8,
129.0, 129.2, 129.7, 129.8, 129.9, 130.3, 133.3, 133.4,
133.5, 134.0 (aromatic carbons), 135.9 (C6), 162.6, 165.0,
165.47, 165.49 (PhCO£4), FD-MS (rel. int., %) m/z¼594
(100, Mþ), 105 (36, PhCOþ), FD-HRMS; found: m/z
594.1381. Calcd for C34H26O8S: Mþ, 594.1348.
4.11.9. Physical data for 31. Mp¼145–146 8C (needles,
from hexane/EtOAc (50:50)), [a]2D3¼217.7 (c 0.73,
4.11.4. Physical data for 26. [a]2D3¼219.6 (c 6.08, CHCl3),
1
1
IR (film), 1730, 1270, 1110, 710 cm21, H NMR (CDCl3),
CHCl3), IR (KBr) 3430, 1640, 1295, 1225, 715 cm21, H
2.98 (1H, dd, J¼4.4, 13.2 Hz, C1HH), 3.24 (1H, dd,
J¼11.2, 13.2 Hz, C1HH), 3.91 (1H, s, OH), 4.46, 4.56 (each
1H, d, J¼11.7 Hz, C6HH), 5.45 (1H, ddd, J¼4.4, 9.7,
11.2 Hz, C2H), 5.86 (1H, d, J¼9.7 Hz, C4H), 6.15 (1H, t,
J¼9.7 Hz, C3H), 7.08–7.45 (12H, aromatic protons), 7.65–
7.90 (8H, aromatic protons), 13C NMR (CDCl3) d 26.3 (C1),
68.3 (C6), 71.6 (C3), 73.9 (C2), 75.4 (C4), 82.7 (C5), 128.1,
128.3, 128.4, 128.5, 128.6, 128.8, 129.0, 129.2, 129.5,
129.8, 129.86, 129.93, 133.0, 133.3, 133.4, 133.6 (aromatic
carbons), 165.6, 165.7, 165.8, 166.9 (PhCO£4), EI-MS (rel.
int., %) m/z¼594 (0.1, Mþ), 472 (0.3, [M2PhCOOH]þ),
105 (100, PhCOþ), EI-HRMS; found: m/z 594.1322. Calcd
for C34H26O8S: Mþ, 594.1348.
NMR (CDCl3) d 1.41, 1.43 (each 3H, s, C(CH3)2), 2.14
(3H, s, CH3CO), 2.82 (1H, dd, J¼3.4, 11.7 Hz, C1HH),
3.04 (1H, dd, J¼10.7, 11.7 Hz, C1HH), 3.34 (1H, s, OH),
3.91 (1H, dt, J¼3,4, 10.7 Hz, C2H), 3.98 (1H, t, J¼10.7 Hz,
C3H), 4.36, 4.52 (each 1H, d, J¼11.7 Hz, C6HH), 5.43
(1H, d, J¼10.7 Hz, C4H), 7.44–8.04 (5H, aromatic
protons), 13C NMR (CDCl3) d 20.9, (CH3CO), 26.6, 27.0
(C(CH3)2), 28.1 (C1), 67.9 (C6), 74.5 (C4), 76.9 (C3), 77.7
(C2), 84.2 (C5), 110.2 (C(CH3)2), 128.6, 129.0, 130.0, 133.6
(aromatic carbons), 166.6, 170.0 (CH3CO and PhCO),
EI-MS (rel. int., %) m/z¼367 (0.8, [M2CH3]þ), 307
(1.6, [M2acetone–OH]þ), 105 (100, PhCOþ), EI-HRMS;
found: m/z 367.0831. Calcd for C17H19O7S: [M2CH3]þ,
367.0852.
4.11.5. Physical data for 28. [a]2D3¼þ153.1 (c 1.96,
1
CHCl3), IR (film), 1725, 1260, 1095, 705 cm21, H NMR
4.12. Acetylation of 15 giving 1-acetoxy-6-O-benzoyl-1,5-
dideoxy-3,4-O-isopropylidene-2-O-methoxymetyl-5-
thio-a-D-glucopyranose (a-16) and its b-isomer (b-16)
(C6D6), 2.94 (1H, dd, J¼5.4, 13.7 Hz, C1HH), 2.99 (1H, dd,
J¼3.0, 13.7 Hz, C1HH), 5.03, 5.08 (each 1H, d, J¼13.1 Hz,
C6HH), 5.58 (1H, ddd, J¼3.0, 4.4, 5.4 Hz, C2H), 6.43 (1H,
d, J¼4.4 Hz, C3H), 6.85–7.10 (12H, aromatic protons),
7.94–8.28 (8H, aromatic protons), 13C NMR (C6D6, Signals
for C4 and C5 could not be detected probably due to those
relaxation time) d 27.0 (C1), 61.0 (C6), 68.1 (C3), 68.6
(C2), 128.1, 128.3, 128.4, 128.5, 128.6, 128.8, 129.0, 129.2,
A mixture of the Pummerer product obtained in Section
4.7.2 and Ac2O (0.2 mL, excess) was stirred in pyridine
(1.0 mL) at room temperature for 30 min. After concen-
tration in vacuo, silica gel column chromatography
(benzene/EtOAc¼90:10) gave a diastereomeric mixture of

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6843
16 (11 mg, 66%). Analytical sample was further purified by
preparative silica gel column chromatography (benzene/
EtOAc¼80:20).
(a/b¼80:20). Assignments of the signals for the main
1
isomer and some for the minor isomer are described. H
NMR (CDCl3, a¼0.8, b¼0.2) d 3.76 (1H£b, dt, J¼9.3,
5.4 Hz, C5H (minor)), 3.96 (1H£a, dt, J¼3.9, 10.3 Hz, C5H
(major)), 4.45, 4.50 (each 1H£a, dd, J¼3.9, 12.2 Hz, C6HH
(major)), 4.63 (1H£b, dd, J¼4.9, 11.7 Hz, C6HH (minor)),
5.75 (1H£a, dd, J¼3.0, 10.3 Hz, C2H (major)), 5.95 (1H£a,
t, J¼10.3 Hz, C4H (major)), 6.19 (1H£a, t, J¼10.3 Hz,
C3H (major)), 6.36 (1H£b, d, J¼7.8 Hz, C1H (minor)), 6.54
(1H£a, d, J¼3.0 Hz, C1H (major)), 7.08–7.56 (15H,
aromatic protons), 7.67–8.06 (10H, aromatic protons),
EI-MS (rel. int. %) m/z¼595 (0.1, [M2PhCOO]þ), 472
(1.9, [M22£PhCOOH]þ), 350 (21, [M23£PhCOOH]þ),
105 (100, PhCOþ), EI-HRMS; Found m/z 595.1426. Calcd
for C34H27O8S: [M2PhCOO]þ, 595.1427.
4.12.1. Physical data for a-16. [a]2D3¼þ91.5 (c 0.94,
CHCl3), IR (film) 2985, 2895, 1750, 1725, 1270, 1215,
1110, 1045, 1020, 710 cm21, 1H NMR (C6D6) d 1.28, 1.29
(each 3H, s, C(CH3)2), 1.64 (3H, s, CH3CO), 3.20 (3H, s,
CH3O), 3.63 (2H, C4H, C5H), 4.01 (1H, dd, J¼7.8,
10.2 Hz, C3H), 4.10 (1H, dd, J¼3.4, 10.2 Hz, C2H), 4.32
(1H, dd, J¼7.3, 11.7 Hz, C6HH), 4.56, 4.71 (each 1H, d,
J¼6.8 Hz, OCHHO), 4.80 (1H, dd, J¼3.4, 11.7 Hz, C6HH),
6.40 (1H, d, J¼3.4 Hz, C1H), 6.97–7.08 (3H, aromatic
protons), 8.12 (2H, aromatic protons), 13C NMR (C6D6) d
20.5 (CH3CO), 26.7, 27.0 (C(CH3)2), 43.1 (C5), 55.4
(CH3O), 63.9 (C6), 73.5 (C1), 77.5 (C2), 78.0 (C3), 78.6
(C4), 95.8 (OCH2O), 109.6 (C(CH3)2), 128.5, 130.0, 130.3,
133.1 (aromatic carbons), 165.8, 168.8 (CH3CO and PhCO),
EI-MS (rel. int., %) m/z¼411 (10, [M2CH3]þ), 304 (18,
[M2PhCOOH]þ), 105 (100, PhCOþ), FD-MS (rel. int., %)
m/z¼426 (16, Mþ), 411 (100, [M2CH3]þ), EI-HRMS;
found m/z 411.1121. Calcd for C19H23O8S: [M2CH3]þ,
411.1114.
4.13.2. Preparation from 18. A mixture of 1,2,3,4,6-O-
pentaacetyl-5-deoxy-5-thio-D-glucopyranose 18 (72.0 mg,
177 mmol), prepared according to Driguez et al.,30 and
NaOMe (57.4 mg, 1.06 mmol) in MeOH (1.0 mL) was
stirred at room temperature for 12 h. After concentration in
vacuo, the residue was diluted with H2O (2.0 mL), then was
passed through ion exchange resin (DOWEX 50W-X4, Hþ
form). The eluate was concentrated in vacuo. The residue
was stirred with BzCl (0.2 mL, 1.72 mmol) in pyridine
(0.5 mL) at room temperature for 12 h. The mixture was
poured into saturated aqueous NaHCO3 solution and
extracted with EtOAc. The combined extracts were washed
with 2 M aqueous HCl and brine successively, dried over
MgSO4, and then concentrated in vacuo. Silica gel column
chromatography of the residue (hexane/EtOAc¼85:15)
gave 17 (85.0 mg, 67% in two steps) as an anomeric
mixture (a/b¼90:10). The 1H NMR spectrum of this sample
was identical except for the isomeric ratio with that of
described in Section 4.13.1.
4.12.2. Physical data for b-16. [a]2D3¼243.4 (c 1.45,
CHCl3), IR (film) 2930, 2895, 1755, 1725, 1270, 1215,
1105, 1030, 710 cm21, 1H NMR (C6D6) d 1.25, 1.27 (each
3H, s, C(CH3)2), 1.52 (3H, s, CH3CO), 3.15 (1H, ddd,
J¼5.8, 7.3, 9.2 Hz, C5H), 3.21 (3H, s, CH3O), 3.59 (1H, t,
J¼9.2 Hz, C3H), 3.88 (1H, t, J¼9.2 Hz, C4H), 4.23 (1H, dd,
J¼4.8, 9.2 Hz, C2H), 4.30 (1H, dd, J¼7.8, 11.2 Hz, C6HH),
4.66 (1H, d, J¼6.9 Hz, OCHHO), 4.69 (1H, dd, J¼5.4,
11.2 Hz, C6HH), 4.82 (1H, d, J¼6.9 Hz, OCHHO), 6.91
(1H, d, J¼4.8 Hz, C1H), 7.01–7.10 (3H, aromatic protons),
8.16 (2H, aromatic protons), 13C NMR (C6D6) d 20.2
(CH3CO), 26.9, 27.1 (C(CH3)2), 43.9 (C5), 55.4(CH3O),
65.4 (C6), 76.1 (C4), 76.3 (C1), 79.5(C2), 81.7(C3), 95.9
(OCH2O), 110.9(C(CH3)2), 128.5, 130.0, 130.5, 133.0
(aromatic carbons), 165.9, 168.2 (CH3CO and PhCO),
EI-MS (rel. int., %) m/z¼411 (7.0, [M2CH3]þ), 364 (6.3,
[M2MOMOH]þ), 304 (39, [M2PhCOOH]þ), 105 (100,
PhCOþ), FD-MS (rel. int., %) m/z¼426 (29, Mþ), 411 (100,
[M2CH3]þ), EI-HRMS; found: m/z 411.1137. Calcd for
C19H23O8S: [M2CH3]þ, 411.1114.
4.14. 6-O-tert-Butyldimethylsilyl-3,4-O-isopropylidene-
2,5-O-bis(methanesulfonyl)-D-mannose (34)
4.14.1. Protection of terminal alcohols as the bis-TBDMS
ether. A mixture of 3,4-O-isopropylidene-D-mannitol (33)
(102.6 mg, 462 mmol), TBDMSCl (139.2 mg, 923 mmol),
and Et3N (0.19 mL, 1.39 mmol) in DMF (3 mL) was stirred
at room temperature for 30 min. The mixture was poured
into saturated aqueous NaHCO3 solution and extracted with
Et2O. The combined extracts were washed with saturated
aqueous NH4Cl and brine successively, dried over MgSO4,
and then concentrated in vacuo. Silica gel column
chromatography of the residue (hexane/EtOAc¼92:8)
gave the corresponding 1,6-bisTBDMS ether (208 mg,
100%) as an oil. [a]2D3¼þ15.3 (c 1.14, CHCl3), IR (film)
3400, 2925, 2855, 1465, 1375, 1255, 1215, 1070 cm21, 1H
NMR (CDCl3) d 0.04 (12H, s, Si(CH3)2£2), 0.85 (18H, s,
SiC(CH3)3£2), 1.30 (6H, s, C(CH3)2), 3.37 (2H, br, OH£2),
3.58 (2H, C2H, C5H), 3.65 (2H, dd, J¼5.8, 10.2 Hz, C1HH,
C6HH), 3.83 (4H, C1HH, C3H, C4H, C6HH), 13C NMR
(CDCl3) d 25.4 (Si(CH3)2£2), 18.3 (SiC(CH3)3£2), 25.8
(SiC(CH3)3£2), 26.9 (C(CH3)2), 64.4 (C1, C6) 73.0 (C2,
C5), 79.3 (C3, C4), 109.1 (C(CH3)2), EI-MS (rel. int., %)
m/z¼451 (0.8, [MþH]þ), 449 (0.1, [M2H]þ), 435 (7.0,
[M2CH3]þ), 393 (9.7, [M2tBu]þ), 335 (19, [M2tBu–
acetone]þ), 117 (100), EI-HRMS; found: m/z 435.2627.
Calcd for C20H43O6Si2: [M2CH3]þ, 435.2598.
4.13. 1,2,3,4,6-O-Pentabenzoyl-5-deoxy-5-thio-D-
glucopyranose (17)
4.13.1. Preparation from 16. A solution of 16 (22.0 mg,
51.5 mmol) in 50% aqueous TFA was stirred at room
temperature for 3 h. After concentration in vacuo, the
residue was stirred with BzCl (59.9 mL, 258 mmol) in
pyridine (300 mL) at room temperature for 15 h. The
mixture was poured into saturated aqueous NaHCO3
solution and extracted with Et2O. The combined extracts
were washed with 2 M aqueous HCl and brine successively,
dried over MgSO4, and then concentrated in vacuo. Silica
gel column chromatography of the residue (hexane/
EtOAc¼85:15) gave 17 (25.0 mg, 63% two steps) as an
anomeric mixture (a/b¼80:20). [a]1D9¼þ161 (c 3.40,
CHCl3), IR (film) 1730, 1265, 1105, 1070, 705 cm21, The
1H NMR spectrum of this sample showed that it consists of
the two isomers arising from the C1 anomeric position

6844
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
4.14.2. Mesylation of the 2,5-hydroxy groups. A mixture
of the product (1.76 g, 3.90 mmol), MsCl (604 mL,
7.81 mmol), and Et3N (1.63 mL, 11.7 mmol) in CH2Cl2
(15 mL) was stirred at 0 8C for 30 min. The mixture was
poured into H2O, and extracted with EtOAc. The combined
extracts were washed with brine, dried over MgSO4, and
then concentrated in vacuo. Silica gel column chromato-
graphy of the residue (hexane/EtOAc¼95:5) gave the
corresponding 2,5-bismesylate ether (2.35 mg, 99%) as an
oil. [a]1D7¼þ17.3 (c 1.58, CHCl3), IR (film) 2925, 2850,
over MgSO4, and then concentrated in vacuo. Silica gel
column chromatography of the residue (hexane/
EtOAc¼85:15) gave 34 (59.1 mg, 100%). 1H NMR
(CDCl3)
d 0.09 (6H, s, Si(CH3)2), 0.89 (9H, s,
SiC(CH3)3), 1.40, 1.43 (each 3H, s, C(CH3)2), 3.13, 3.19
(each 3H, s, SO2CH3), 3.83 (1H, dd, J¼6.8, 12.2 Hz,
C6HH), 3.97 (1H, dd, J¼2.9, 12.2 Hz, C6HH), 4.30 (1H, t,
J¼7.8 Hz, C4H), 4.56 (1H, dd, J¼2.9, 7.8 Hz, C3H), 4.67
(1H, ddd, J¼2.9, 6.8, 7.8 Hz, C5H), 4.98 (1H, d, J¼2.9 Hz,
C2H), 9.66 (1H, s, C1H). This sample was subjected to the
next step without further purification.
1
1700, 1105, 1025 cm21, H NMR (CDCl3) d 0.00 (12H, s,
Si(CH3)2£2), 0.81 (18H, s, SiC(CH3)3£2), 1.32 (6H, s,
C(CH3)2), 3.01 (6H, s, SO2CH3£2), 3.75 (2H, dd, J¼6.3,
11.7 Hz, C1HH, C6HH), 3.92 (2H, dd, J¼3.4, 11.7 Hz,
C1HH, C6HH), 4.26 (2H, C3H, C4H), 4.62 (2H, C2H,
C5H), 13C NMR (CDCl3) d 25.6 (Si(CH3)2£2), 18.2
(SiC(CH3)3£2), 25.7 (SiC(CH3)3£2), 26.9 (C(CH3)2), 38.6
(SO2CH3£2), 62.4 (C1, C6) 76.1 (C2, C5), 82.3 (C3, C4),
110.9 (C(CH3)2), EI-MS (rel. int., %) m/z¼591 (20,
[M2CH3]þ), 549 (8.2, [M2tBu]þ), 153 (100), EI-HRMS;
found: m/z 591.2138. Calcd for C22H47O10Si2S2:
[M2CH3]þ, 591.2149.
4.14.6. (1R)-6-O-tert-Butyldimethylsilyl-1-deuterio-3,4-
O-isopropylidene-2,5-O-bis(methanesulfonyl)-D-manni-
tol (35). To a mixture of 34 (689 mg, 1.40 mmol) and Ce
(III) chloride (1.04 g, 2.81 mmol) in MeOH (10 mL),
NaBD4 (117 mg, 2.80 mmol) was added at room tempera-
ture. After stirring for 1 h, the mixture was poured into H2O,
and extracted with EtOAc. The combined extracts were
washed with brine, dried over MgSO4, and then concen-
trated in vacuo. Silica gel column chromatography of the
residue (hexane/EtOAc¼80:20) gave 35 (626 mg, 91%) as
an oil. [a]1D7¼þ16.6 (c 1.60, CHCl3), IR (film) 3510, 2935,
that the sample consists of 90:10 diastereomeric isomers, 1H
NMR (C6D6) d 0.01, 0.02 (each 3H, s, Si(CH3)2), 0.89 (9H,
s, SiC(CH3)3), 1.20, 1.22 (each 3H, s, C(CH3)2), 2.52, 2.56
(each 3H, s, SO2CH3), 3.65 (1H£0.1, br, C1HH), 3.79 (1H,
dd, J¼6.4, 11.7 Hz, C6HH), 3.82 (1H£0.9, br, C1HH), 4.06
(1H, dd, J¼3.0, 11.7 Hz, C6HH), 4.16 (1H, t, J¼6.8 Hz,
C4H), 4.31 (1H, t, J¼6.8 Hz, C3H), 4.60 (1H, dd, J¼3.9,
6.8 Hz, C2H), 4.66 (1H, ddd, J¼3.0, 3.4, 6.8 Hz, C5H), 13C
NMR (C6D6) d 25.48 (Si(CH3)2), 18.5 (SiC(CH3)3), 26.0
(SiC(CH3)3), 27.0 (C(CH3)2), 38.2, 38.4 (SO2CH3£2), 61.7
(C1, observed as triplet due to deuterium), 63.5 (C6) 76.5
(C4), 77.2 (C3), 82.1 (C2), 82.5 (C5), 111.5 (C(CH3)2),
EI-MS (rel. int., %) m/z¼478 (14, [M2CH3]þ), 436 (2.6,
[M2tBu]þ), 153 (100), EI-HRMS; found: m/z 478.1332.
Calcd for C16H32DO10S2Si: [M2CH3]þ, 478.1346.
1
4.14.3. Desilylation giving the corresponding mono-
alcohol. A mixture of the product obtained in Section
4.14.2 (1.84 g, 3.04 mmol), 1 M TBAF in THF (3.0 mL,
3.0 mmol), and AcOH (364 mg, 2.80 mmol) in THF
(20 mL) was stirred at 0 8C for 3 h. The mixture was poured
into H2O, and extracted with EtOAc. The combined extracts
were washed with brine, dried over MgSO4, and then
concentrated in vacuo. Silica gel column chromatography of
the residue (hexane/EtOAc¼75:25) gave the corresponding
monoalcohol (1.01 mg, 67%), recovered bis-TBDMS
ether (368 mg, 20%), and the diol (115 mg, 10%) as an
2855, 1340, 1175 cm21, The H NMR spectrum indicated
1
oil. The H NMR spectra of the recovered bis-TBDMS
ether and diol were identical with those of the authentic
samples.
4.14.4. Physical data for the mono-TBDMS ether.
[a]1D7¼þ22.0 (c 0.48, CHCl3), IR (film) 3510, 2935, 2855,
1
1340, 1175 cm21, H NMR (CDCl3) d 20.01, 0.00 (each
4.15. (6R)-6-O-Benzoyl-6-deuterio-3,4-O-isopropyl-
idene-2,5-O-bis(methanesulfonyl)-D-mannose (36)
3H, s, Si(CH3)2), 0.82 (9H, s, SiC(CH3)3), 1.31, 1.32 (each
3H, s, C(CH3)2), 3.02, 3.04 (each 3H, s, SO2CH3), 3.74 (1H,
dd, J¼4.4, 11.7 Hz, C6HH), 3.76 (1H, dd, J¼3.0, 11.7 Hz,
C1HH), 3.87 (1H, dd, J¼3.4, 11.7 Hz, C1HH), 3.92 (1H, dd,
J¼3.4, 11.7 Hz, C6HH), 4.16 (1H, t, J¼6.8 Hz, C3H), 4.31
(1H, t, J¼6.8 Hz, C4H), 4.60 (1H, ddd, J¼3.0, 3.4, 6.8 Hz,
C2H), 4.66 (1H, ddd, J¼3.4, 4.4, 6.8 Hz, C5H), 13C NMR
(CDCl3) d 25.2 (Si(CH3)2), 18.6 (SiC(CH3)3), 26.1
(SiC(CH3)3), 27.2, 27.3, (C(CH3)2), 38.8, 39.1
(SO2CH3£2), 61.9, 62.9 (C1, C6) 76.4,77.0 (C2, C5),
82.0, 83.2 (C3, C4), 111.5 (C(CH3)2), EI-MS (rel. int., %)
m/z¼477 (14, [M2CH3]þ), 435 (3.1, [M2tBu]þ), 153
(100), EI-HRMS; found: m/z 477.1295. Calcd for
C16H33O10SiS2: [M2CH3]þ, 477.1284.
4.15.1. Benzoylation of 35. A mixture of 35 (615 mg,
1.24 mmol), BzCl (210 mL, 1.86 mmol), and pyridine
(200 mL, 2.59 mmol) in CH2Cl2 (10 mL) was stirred at
room temperature for 12 h. The mixture was poured into
saturated aqueous NaHCO3 solution and extracted with
CH2Cl2. The combined extracts were washed with brine,
dried over MgSO4, and then concentrated in vacuo. Silica
gel column chromatography of the residue (hexane/
EtOAc¼85:15) gave the corresponding benzoate (674 mg,
90%) as an oil. [a]1D7¼þ28.8 (c 0.67, CHCl3), IR (film)
1
3445, 2930, 2855, 1730, 1360, 1175 cm21. The H NMR
spectrum indicated that the sample consists of 90:10
diastereomeric isomers, 1H NMR (C6D6) d 0.03, 0.04
(each 3H, s, Si(CH3)2), 0.90 (9H, s, SiC(CH3)3), 1.21 (6H, s,
C(CH3)2), 2.46, 2.59 (each 3H, s, SO2CH3), 3.81 (1H, dd,
J¼5.4, 11.7 Hz, C6HH), 4.08 (1H, dd, J¼2.9, 11.7 Hz,
C6HH), 4.55 (1H, dd, J¼6.4, 7.3 Hz, C4H), 4.69 (1H, t,
J¼6.4 Hz, C3H), 4.83 (2H, C1H, C5H), 5.16 (1H, dd,
J¼2.4, 6.4 Hz, C2H), 7.08 (3H, aromatic protons), 8.25 (2H,
aromatic protons), 13C NMR (C6D6) d 25.47, 25.43
4.14.5. Oxidation giving 34. A mixture of the mono-
TBDMS ether obtained in Section 4.14.3 (59.2 mg,
120 mmol) and Dess-Martin reagent (76.4 mg, 180 mmol)
in CH2Cl2 (2 mL) was stirred at room temperature for 3 h.
The mixture was poured into a mixture of saturated aqueous
NaHCO3 and 10% Na2S2O3 (10 mL) and extracted with
ether. The combined extracts were washed with brine, dried

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6845
(Si(CH3)2), 18.5 (SiC(CH3)3), 26.0 ((SiC(CH3)3), 26.95,
27.02 (C(CH3)2), 38.3, 38.4 (SO2CH3£2), 63.1, (C6), 63.2
(C1, observed as triplet due to deuterium), 76.1 (C4) 77.7
(C3), 78.5 (C2), 81.7 (C5), 111.5 (C(CH3)2), 128.6, 130.17,
130.20, 133.2 (aromatic carbons), 166.2 (PhCO), EI-MS
(rel. int., %) m/z¼582 (17, (M2CH3)þ), 540 (24,
[M2tBu]þ), 105 (100, PhCOþ), EI-HRMS; found: m/z
582.1606. Calcd for C23H36DO11S2Si: [M2CH3]þ,
582.1608.
residue (hexane/EtOAc¼70:30) gave 37 (660 mg, 85% in
two steps) as an oil. [a]D17¼þ38.0 (c 0.50, CHCl3), IR (film)
1
3540, 2940, 1725, 1355, 1175, 915 cm21. The H NMR
spectrum indicated that the sample consists of 90:10
diastereomeric isomers, thus, the signals for the major
product are reported. 1H NMR (C6D6) d 1.16, 1.19 (each 3H,
s, C(CH3)2), 2.45, 2.56 (each 3H, s, OSO2CH3), 3.86 (1H,
br, C1H), 4.41 (1H, dd, J¼6.4, 6.8 Hz, C3H), 4.55 (1H. dd,
J¼5.4, 6.4 Hz, C4H), 4.76 (2H, C2H, C6H), 5.15 (1H, dd,
J¼2.4, 5.4 Hz, C5H), 7.08 (3H, aromatic protons), 8.23 (2H,
aromatic protons), 13C NMR (C6D6) d 26.8, 26.9 (C(CH3)2),
38.1, 38.4 (OSO2CH3), 62.0, 63.4 (C1, C6 each signals were
observed as triplet because of deuterium attached.), 76.5
(C3), 77.7 (C4), 78.6 (C5), 81.7 (C2), 111.5 (C(CH3)2),
130.1, 130.2, 133.3 (aromatic carbons), 166.3 (PhCO),
EI-MS (rel. int., %) m/z¼469 (12, [M2CH3]þ), 372 (19,
[M2CH3–MsOH]þ), 105 (100, PhCOþ), EI-HRMS; found:
m/z 469.0849. Calcd for C17H21D2O11S2: [M2CH3]þ,
469.0805.
4.15.2. Desilylation. A mixture of the benzoate obtained in
Section 4.15.1 (670 mg, 1.12 mmol), 1.0 M TBAF in THF
(1.68 mL, 1.68 mmol), and AcOH (130 mL, 2.24 mmol) in
THF (8.0 mL) was stirred at room temperature for 30 min.
The mixture was poured into H2O, and extracted with
EtOAc. The combined extracts were washed with brine,
dried over MgSO4, and then concentrated in vacuo.
Silica gel column chromatography of the residue
(hexane/EtOAc¼75:25) gave the corresponding alcohol
(533 mg, 98%) as an oil. [a]1D7¼þ25.8 (c 1.56, CHCl3), IR
1
(film) 3535, 2940, 1725, 1345, 1175, 915 cm21. The H
4.15.5. (1R,2S,3R,4R,5S,6R)-1,6-Dideuterio-1,2-5,6-bis-
A
NMR spectrum indicated that the sample consists of 90:10
diastereomeric isomers, thus, the signals for the major
epoxy-3,4-O-isopropylidene-3,4-hexandiol
(38).
mixture of 37 (146 mg, 302 mmol) and K2CO3 (208 mg,
1.51 mmol) in a mixture of MeOH (2.0 mL) and CH2Cl2
(2.0 mL) was stirred at 0 8C. The mixture was allowed to
warm to room temperature. After 4 h, ether (20 mL) was
added and the mixture was stirred for 30 min at room
temperature. After filtration under suction, the mixture was
poured into H2O, and extracted with CH2Cl2. The combined
extracts were washed with brine, dried over MgSO4, and
then concentrated in vacuo. Silica gel column chromato-
graphy of the residue (hexane/EtOAc¼70: 30) gave 38
(37.8 mg, 67%) as an oil. [a]1D7¼215.4 (c 0.50, CHCl3), IR
1
isomer are described. H NMR (C6D6) d 1.14, 1.18 (each
3H, s, C(CH3)2), 2.40, 2.51 (each 3H, s, SO2CH3), 3.67 (1H,
dd, J¼5.4, 12.2 Hz, C1HH), 3.85 (1H, dd, J¼3.4, 12.2 Hz,
C1HH), 4.38 (1H, dd, J¼6.4, 6.8 Hz, C3H), 4.54 (1H, dd,
J¼5.4, 6.4 Hz, C4H), 4.73 (2H, C2H, C6H), 5.13 (1H, dd,
J¼2.4, 5.4 Hz, C5H), 7.06 (3H, aromatic protons), 8.23 (2H,
aromatic protons), 13C NMR (C6D6) d 26.8, 26.9 (C(CH3)2),
38.1, 38.4 (SO2CH3), 62.1, (C1), 63.4 (C6, observed as
triplet due to deuterium), 76.5 (C3) 77.7 (C4), 78.6 (C5),
81.8 (C2), 111.5 (C(CH3)2), 127.8, 128.7, 130.2 133.3
(aromatic carbons), 166.3 (PhCO), EI-MS (rel. int., %)
m/z¼468 (17, [M2CH3]þ), 372 (19, [M2CH3–MsOH]þ),
105 (100, PhCOþ), EI-HRMS; found: m/z 468.0704. Calcd
for C17H22DO11S2: [M2CH3]þ, 468.0744.
1
(film) 1990, 1245, 1215, 1050, 860 cm21. The H NMR
spectrum indicated that the sample consists of 90:10
diastereomeric isomers, thus, the signals for the major
product are reported. 1H NMR (C6D6) d 1.33, (6H, s,
C(CH3)2), 2.30 (2H, d, J¼2.9 Hz, C1H, C6H), 2.54 (2H, dd,
J¼2.9, 3.4 Hz, C2H, C5H), 3.62 (2H, dd, J¼2.0, 3.4 Hz,
C3H, C4H), 13C NMR (C6D6) d 26.8 (C(CH3)2), 42.7 (C1
and C6, the signal was observed as triplet because of
deuterium attached.), 50.8 (C2, C5) 78.3 (C3, C4), EI-MS
(rel. int., %) m/z¼173 (56, [M2CH3]þ), 43 (100),
EI-HRMS; found: m/z 173.0799. Calcd for C8H9D2O4:
[M2CH3]þ, 173.0781.
4.15.3. Oxidation giving 36. A mixture of the alcohol
obtained in Section 4.15.2 (780 g, 1.61 mmol) and Dess-
Martin reagent (684 mg, 1.61 mmol) in CH2Cl2 (7.0 mL)
was stirred at room temperature for 2 h. The mixture was
poured into a mixture of saturated aqueous NaHCO3
(50 mL) and 10% Na2S2O3 (10 mL) and extracted with
ether. The combined extracts were washed with brine, dried
over MgSO4, then concentrated in vacuo to give the crude
aldehyde 36 (803 mg), 1H NMR (CDCl3) d 1.32, 1.35 (each
3H, s, C(CH3)2), 2.90, 3.10 (each 3H, s, OSO2CH3), 4.37
(2H, C3H, C4H), 4.48 (1H, dd, J¼3.4, 7.3 Hz, C2H), 4.70
(1H, d, J¼2.4 Hz, C6H), 4.91 (1H, dd, J¼2.4, 6.8 Hz, C5H),
7.36 (2H, aromatic protons), 7.48 (1H, m, aromatic proton),
7.95 (2H, aromatic protons), 9.68 (1H, s, C1H), This sample
was subjected to the next step without purification.
4.16. (1R,6R)-6-O-Benzoyl-1,5-dideoxy-1,6-dideuterio-
3,4-O-isopropylidene-5-thio-D-glucopyranose (39)
4.16.1. Thiepane formation from 38. According to the
established procedure by Merrer et al., a mixture of 38
(120 mg, 638 mmol) and Na2S·9H2O (199 mg, 829 mmol)
in DMF (5.0 mL) was stirred at room temperature for 11 h.
After concentration in vacuo at 50 8C, the residue was
purified by silica gel column chromatography (benzene/
EtOAc¼60:40) to afford the corresponding thiepane
(110 mg, 77%) as an oil. [a]1D7¼þ80.1 (c 0.90, MeOH),
IR (film) 3480, 1240, 1220 cm21, 1H NMR (CD3OD) d 1.39
(6H, s, C(CH3)2), 2.62 (2H, d, J¼5.9 Hz, C2H, C7H), 3.83
(2H, dt, J¼2.4, 5.9 Hz, C3H, C6H), 3.94 (2H, C4H, C5H),
EI-MS (rel. int., %) m/z¼207 (37, [M2CH3]þ), 204 (91,
[M2H2O]þ), 156 (100), EI-HRMS; found: m/z 207.0674.
Calcd for C8H11D2O4S: [M2CH3]þ, 207.0658.
4.15.4. (1R,6R)-6-O-Benzoyl-1,6-dideuterio-3,4-O-iso-
propylidene-2,5-O-bis(methanesulfonyl)-D-mannitol
(37). To a mixture of the crude aldehyde 36 (803 mg) and
Ce (III) chloride (1.36 g, 3.65 mmol) in MeOH (10 mL),
NaBD4 (153 mg, 3.66 mmol) was added at room tempera-
ture. After stirring for 1 h, the mixture was poured into H2O,
and extracted with EtOAc. The combined extracts were
washed with brine, dried over MgSO4, and then concen-
trated in vacuo. Silica gel column chromatography of the

6846
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
4.16.2. Ring contraction by Mitsunobu reaction giving
39. To a mixture of the product obtained in Section 4.16.1
(135 mg, 608 mmol), benzoic acid (96.5 mg, 790 mmol),
and PPh3 (207 mg, 790 mmol) in THF (5.0 mL), diethyl
azodicarboxylate (40% toluene solution, 310 mL,
790 mmol) was added and the mixture was stirred at room
temperature for 2 h. The mixture was poured into H2O and
extracted with EtOAc. The combined extracts were washed
with brine, dried over MgSO4, and then concentrated in
vacuo. Silica gel column chromatography of the residue
(hexane/EtOAc¼75:25) gave 39 (187 mg, 94%) as an oil,
[a]2D3¼þ80.1 (c 1.42 CHCl3), IR (film) 3450, 2985, 1720,
1270, 1230, 1065, 710 cm21, 1H NMR (C6D6) d 1.31, 1.32
(each 3H, s, C(CH3)2), 2.57 (1H, d, J¼10.3 Hz, C1H), 3.17
(1H, t, J¼8.8 Hz, C3H), 3.30 (1H, dd, J¼4.0, 10.3 Hz,
C5H), 3.55 (1H, dd, J¼8.8, 10.3 Hz, C4H), 3.92 (1H, dd,
J¼8.8, 10.3 Hz, C2H), 4.63 (1 h, d, J¼4.0 Hz, C6H), 7.32
(2H, aromatic protons), 7.45 (1H, m, aromatic proton), 7.94
(2H, aromatic protons), EI-MS (rel. int., %) m/z¼311 (4.0,
[M2CH3]þ), 250 (6.0, [M2H2O–acetone]þ), 105 (100,
PhCOþ), EI-HRMS; found: m/z 311.0951. Calcd for
C15H15D2O5S: [M2CH3]þ, 311.0920.
(1H, t, J¼9.3 Hz, C4H), 4.41 (1H, dd, J¼9.3, 10.3 Hz,
C3H), 5.15 (1H, d, J¼4.4 Hz, C6H), 6.13 (1H, t, J¼10.3 Hz,
C2H), 6.97–7.18 (6H, aromatic protons), 8.05–8.17 (4H,
aromatic protons), EI-MS (rel. int., %) m/z¼446 (0.9, Mþ),
431 (0.9, [M2CH3]þ), 324 (1.0, [M2PhCOOH]þ), 266
(5.0, [M2PhCOOH–acetone]þ), 105 (100, PhCOþ),
EI-HRMS; found: m/z 446.1342. Calcd for C23H22D2O7S:
[M2CH3]þ, 446.1366.
4.17. The Pummerer rearrangement of deuterium
labelled 41 giving (1R,6R)-2,6-O-dibenzoyl-5-deoxy-1,6-
dideutreio-3,4-O-isopropylidene-5-thio-D-glucopyranose
(42)
4.17.1. Reaction of eq-41. Treatment of eq-41 (9.3 mg,
20.8 mmol) in a similar manner as described in Section 4.7.1
gave 42 (5.2 mg, 56%) as an oil after silica gel column
chromatography. [a]D19¼þ74.9 (c 0.39 CHCl3), IR (film)
3445, 1720, 1270, 1115, 710 cm21, 1H NMR (C6D6) d 1.26,
1.29 (each 3H, s, C(CH3)2), 3.63 (1H, dd, J¼3.9, 10.7 Hz,
C5H), 3.80 (1H, dd, J¼8.8, 10.7 Hz, C4H), 4.37 (1H, dd,
J¼8.8, 10.8 Hz, C3H), 4.77 (1H, d, J¼3.9 Hz, C6H), 5.52
(1H, d, J¼10.8 Hz, C2H), 6.94–7.17 (6H, aromatic
protons), 8.17–8.20 (4H, aromatic protons), EI-MS (rel.
int., %) m/z¼446 (0.3, Mþ), 431 (0.8, [M2CH3]þ), 324
(3.0, [M2PhCOOH]þ), 266 (1.8, [M2PhCOOH–
acetone]þ), 105 (100, PhCOþ), EI-HRMS; found: m/z
446.1380. Calcd for C23H22D2O7S: [M2CH3]þ, 446.1366.
4.16.3. (1R,6R)-2,6-O-Dibenzoyl-1,5-dideoxy-1,6-
dideuterio-3,4-O-isopropylidene-5-thio-D-glucopyranose
(R)-S-oxide (eq-41) and its (S)-isomer (ax-41). Benzoyl-
ation of 39 (180 mg, 552 mmol) in a similar manner as
described in Section 4.22 gave the corresponding benzoate
(170 mg, 72%) as an oil after silica gel column chromato-
graphy. [a]1D9¼þ86.3 (c 1.05 CHCl3), IR (film) 1720, 1270,
1110, 710 cm21, 1H NMR (C6D6) d 1.24, 1.29 (each 3H, s,
C(CH3)2), 2.35 (1H, d, J¼9.8 Hz, C1H), 3.13 (1H, dd,
J¼3.9, 10.3 Hz, C5H), 3.38 (1H, dd, J¼8.8, 10.3 Hz, C3H),
3.70 (1H, dd, J¼8.8, 10.3 Hz, C4H), 4.82 (1H, d, J¼3.9 Hz,
C6H), 5.47 (1H, dd, J¼9.8, 10.3 Hz, C2H), 6.97–7.10 (6H,
aromatic protons), 8.08–8.19 (4H, aromatic protons),
EI-MS (rel. int., %) m/z¼415 (5.0, [M2CH3]þ), 250 (8.5,
[M2PhCOOH–acetone]þ), 105 (100, PhCOþ), EI-HRMS;
found: m/z 415.1145. Calcd for C22H19D2O6S: [M2CH3]þ,
415.1182.
4.18. Reaction of ax-41
Treatment of ax-41 (8.1 mg, 18.1 mmol) in a similar manner
as described in Section 4.7.1 gave 42 (7.0 mg, 86%) as an oil
after silica gel column chromatography. The 1H NMR
spectrum of the product was identical with that of the
authentic sample prepared in Section 4.17.1.
4.18.1. 1,5-Dideoxy-3,4-O-isopropylidene-2-O-methoxy-
methyl-5-thio-D-glucopyranose (S)-S-oxide (43).
A
mixture of ax-9 (171 mg, 445 mmol) and NaOMe
(48.0 mg, 890 mmol) was stirred in MeOH (5.0 mL) at
room temperature for 20 h. After addition of ion exchange
resin (DOWEX 50W-X4, Hþ form, ca. 100 mg), the
mixture was filtered, then concentrated in vacuo. Silica
gel column chromatography of the residue (CH2Cl2/
acetone¼75:25) gave 43 (142 mg, 100%) as a solid.
Analytical sample was obtained by recrystallization
(hexane/EtOAc¼50:50) giving needles. Mp¼135–136 8C,
[a]2D3¼þ11.9 (c 2.10, MeOH), IR (KB) 3400, 2985, 2930,
Oxidation of the product (170 mg, 395 mmol) in the same
manner as described in Section 4.3.1 gave eq-41 (75.3 mg,
43%) and ax-41 (54.5 mg, 31%) both as oils after silica gel
column chromatography.
4.16.4. Physical data for eq-41. [a]1D9¼þ37.8 (c 0.65
1
CHCl3), IR (film) 1725, 1270, 1110, 1040, 710 cm21, H
NMR (C6D6) d 1.16, 1.24 (each 3H, s, C(CH3)2), 2.77 (1H,
d, J¼9.3 Hz, C1H), 2.96 (1H, dd, J¼3.4, 11.2 Hz, C5H),
3.34 (1H, dd, J¼9.3, 11.2 Hz, C4H), 4.07 (1H, t, J¼9.3 Hz,
C3H), 4.86 (1H, d, J¼3.4 Hz, C6H), 5.37 (1H, t, J¼9.3 Hz,
C2H), 6.96–7.18 (6H, aromatic protons), 8.04–8.17 (4H,
aromatic protons), EI-MS (rel. int., %) m/z¼447 (0.6,
[MþH]þ), 431 (1.4, [M2CH3]þ), 266 (1.1, [M2
PhCOOH–acetone]þ), 105 (100, PhCOþ), EI-HRMS;
found: m/z 431.1115. Calcd for C22H19D2O7S:
[M2CH3]þ, 431.1132.
1
2895, 1155, 1055, 1020 cm21, H NMR (CD3OD) d 1.40,
1.42 (each 3H, s, C(CH3)2), 2.69 (1H, dd, J¼11.3, 14.7 Hz,
C1HH), 3.04 (1H, dt, J¼4.4, 11.3 Hz, C5H), 3.38 (3H, s,
CH3O), 3.62 (1H, dd, J¼4.4, 14.7 Hz C1HH), 3.65 (1H, t,
J¼9.3 Hz, C3H), 3.88 (1H, t, J¼10.7 Hz, C4H), 3.89 (1H,
dd, J¼8.8, 11.7 Hz, C6HH), 4.05 (1H, ddd, J¼0.9, 4.4,
11.7 Hz, C6HH), 4.38 (1H, ddd, J¼3.9, 9.7, 10.7 Hz, C2H),
4.69, 4.83 (each 1H, d, J¼6.9 Hz, OCHHO), 13C NMR
(CD3OD) d 26.9, 27.0 (C(CH3)2), 50.2 (C1), 55.9 (CH3O),
57.8 (C6), 62.9 (C5), 72.3 (C2), 73.7 (C4), 82.7 (C3), 97.0
(OCH2O), 111.0 (C(CH3)2), FD-MS (rel. int., %) m/z¼280
(47, Mþ), 265 (97, [M2Me]þ), 262 (100, [M2H2O]þ), FD-
HRMS; found: m/z 280.0985. Calcd for C11H20O6S: Mþ,
280.0981.
4.16.5. Physical data for ax-41. [a]1D9¼þ49.6 (c 0.52
1
CHCl3), IR (film) 1720, 1270, 1110, 710 cm21, H NMR
(C6D6) d 1.17, 1.31 (each 3H, s, C(CH3)2), 1.64 (1H, d,
J¼10.3 Hz, C1H), 2.70 (1H, dd, J¼4.4, 9.3 Hz, C5H), 3.52

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6847
4.18.2. 1,5-Dideoxy-3,4-O-isopropylidene-6-O-[50-deoxy-
20,30,40,60-O-tetrakis(4-methoxyphenylmethyl)-50-thio-a-
D-glucopyranosyl]-2-O-methoxymethyl-5-thio-D-gluco-
pyranose (S)-S-oxide (45). To a mixture of 43 (30.0 mg,
107 mmol), 2,3,4,6-O-tetrakis(4-methoxyphenylmethyl)-5-
deoxy-5-thio-a-D-glucopyranosyl trichloroacetimidate (44)
(80.0 mg, 97.4 mmol), and MS4A (200 mg) in CH2Cl2
(5.0 mL), TMSOTf (0.9 mL, 4.9 mmol) in CH2Cl2 (100 mL)
was added at 278 8C. The mixture was allowed to warm to
room temperature for 2 h. After addition of Et3N (50 mL,
361 mmol), the mixture was filtered through Celitew pad
and the filtrate was concentrated in vacuo. Silica gel column
chromatography of the residue (benzene/EtOAc¼85:15)
gave 45 (85.0 mg, 93%) as an oil. [a]2D3¼þ68.7 (c 3.8,
CHCl3), IR (film) 2995, 2915, 2835, 1510, 1250, 1100,
(minor)), 3.294 (3H£b, s, CH3O (major)), 3.296 (3H£b, s,
CH3O (minor)), 3.301 (3H£b, s, OCH3 (minor)), 3.306
(3H£b, s, CH3O (major)), 3.310 (3H£b, s, CH3O (major)),
3.318 (3H£b, s, CH3O (major)), 3.321 (3H£b, s, CH3O
(minor)), 3.43 (1H£b, ddd, J¼2.4, 3.9, 10.2 Hz, C5H
(minor) or C50H (minor)), 3.47 (1H£a, dt, J¼3.9, 12.0 Hz,
C5H (major) or C50H (major)), 3.66–4.76 (21H), 4.88–4.94
(2H, m), 4.94 (1H£b, br, C1H (minor) or C10H (minor)),
4.99 (1H£b, d, J¼10.2 Hz, OCHHO (minor) or ArCHHO
(minor)), 5.02 (1H, £ a, d, J¼10.7 Hz, OCHHO (major) or
ArCHHO (major)), 5.03 (1H, d, J¼10.7 Hz, OCHHO or
ArCHHO), 6.79 (8H, aromatic protons), 7.15–7.35 (8H,
aromatic protons). This sample was used for the next step
without further measurement of physical data because of a
mixture of anomers.
1035 cm21 1H NMR (C6D6) d 1.21, 1.31 (each 3H, s,
,
C(CH3)2), 1.64 (1H, dd, J¼11.2, 14.7 Hz, C1HH), 2.54 (1H,
dt, J¼3.9, 11.7 Hz, C5H), 3.08 (3H, s, CH3O), 3.13 (1H, dd,
J¼3.9, 14.7 Hz, C1HH), 3.26 (1H, t, J¼9.3 Hz, C3H),
3.275, 3.278, 3.296, 3.302 (each 3H, s, CH3O£4), 3.75–
3.85 (3H, C05H, C60HH, C6HH), 3.99 0(1H, dd, J¼2.5,
9.3 Hz, C20H), 4.18–4.24 (3H, C4H, C4 H, C60HH), 4.28
(1H, d, J¼11.7 Hz, ArCHHO), 4.34 (1H, t, J¼9.3 Hz,
C30H), 4.42–4.47 (3H, ArCH2O, OCHHO), 4.50 (1H, d,
J¼2.5 Hz, C10H), 4.58 (1H, d, J¼11.2 Hz, ArCHHO), 4.58
(1H, m, C2H), 4.65 (1H, t, J¼10.7 Hz, C6H), 4.73–4.74
(2H, OCHHO, ArCHHO), 5.07 (1H, d, J¼10.3 Hz,
ArCHHO), 5.09 (1H, d, J¼10.8 Hz, ArCHHO), 5.21 (1H,
d, J¼10.8 Hz, ArCHHO), 6.72–7.41 (16H, aromatic
protons), 13C NMR (C6D6) d 26.7, 27.0 (C(CH3)2), 42.3
(C05), 50.2 (C1), 54.66, 54.70, 54.70, 54.72 (CH3O£4), 55.2
(CH3O), 59.2 (C5), 63.3 (C6), 68.0 (C06), 71.4 (C2), 72.8,
72.9, 75.5, 76.0 (ArCH2O£4), 80.7 (C01), 82.5 (C3), 84.1
(C04), 85.3 (C03), 96.1 (C02), 109.7 (OCH2O), 113.93,
113.97, 114.0, 114.1, 129.3, 129.6, 129.68, 129.76, 130.8,
131.2, 131.7, 132.2, 159.52, 159.57, 159.67, 159.76
(aromatic carbons), FD-MS (rel. int., %) m/z¼940 (57,
[MHþ1]þ), 939 (100, [MþH]þ), 938 (99. Mþ), FD-HRMS;
found: m/z 938.3583. Calcd for C49H62O14S2: Mþ,
938.3581.
4.19.2. Physical data for 47 (4,5-olefin). [a]2D2¼þ37.4 (c
0.98, CHCl3), IR (film) 2930, 2835, 1510, 1250, 1035 cm21
,
1H NMR (CDCl3) d 1.33, 1.37 (each 3H, s, C(CH3)2), 2.69
(1H, dd, J¼8.8, 12.7 Hz, C1HH), 2.88 (1H, dd, J¼5.3,
12.7 Hz, C1HH), 3.12 (1H, dt, J¼3.4, 6.3 Hz, C50H), 3.28
(3H, s, CH3O), 3.40 (1H, dd, J¼3.4, 10.2 Hz, C60HH),
3.59–3.80 (16H, CH3O£4, C20H, C40H, C30H, C60H), 3.88
(1H, ddd, J¼5.3, 8.8, 9.3 Hz, C2H), 4.11 (1H, d, J¼11.7 Hz,
C6HH), 4.41–4.52 (6H, ArCHHO£4, C3H, C6HH), 4.58
(1H, d, J¼2.9 Hz, C10H), 4.68–4.80 (7H, ArCHHO£5,
OCH2O), 6.67–7.20 (16H, aromatic protons), 13C NMR
(CDCl3) d 24.9, 26.7 (C(CH3)2), 29.1 (C1), 41.2 (C50),
55.19, 55.23, 55.25, 55.25 (CH3O£4), 55.6 (CH3O), 64.3
(C6), 67.5 (C60), 72.4 (ArCH2O), 72.8 (ArCH2O), 75.1
(ArCH2O), 75.7 (ArCH2O), 76.8 (C2), 77.5 (C3), 78.9
(C10), 81.5 (C40), 83.0 (C30), 83.9 (C20), 95.9 (OCH2O), 97.7
(C(CH3)2), 112.2 (C5), 113.66, 113.70, 113.70, 113.75,
129.39, 129.41, 129.5, 129.7, 130.0, 130.7, 130.8, 131.4
(aromatic carbons), 142.9 (C4), 158.97, 159.0, 159.15,
159.20, (aromatic carbons), FD-MS (rel. int., %) m/z¼921
(65, [MH]þ), 920 (100, Mþ), FD-HRMS; found: m/z
920.3483. Calcd for C49H60O13S2: Mþ, 920.3475.
4.19.3. Physical data for 48 (5,6-olefin). [a]2D2¼221.8 (c
0.85, CHCl3), IR (film) 2930, 2835, 1610, 1510, 1250, 1035,
4.19. The Pummerer rearrangement of 45 giving 5-
deoxy-3,4-O-isopropylidene-6-O-[50-deoxy-20,30,40,60-O-
tetrakis(4-methoxyphenylmethyl)-50-thio-a-D-gluco-
pyranosyl]-2-O-methoxymethyl-5-thio-D-glucopyranose
(46) and its isomers 47, 48
515 cm21 1H NMR (C6D6) d 1.34, 1.38 (each 3H, s,
,
C(CH3)2), 2.58 (2H, C1H2), 3.08 (3H, s, CH3O), 3.27 (6H, s,
CH3O£2), 3.29, 3.31 (each 3H, s, CH3O), 3.46 (1H, t,
J¼8.8 Hz, C3H), 3.46 (1H, m, C60HH), 3.63 (1H, dt, J¼3.9,
6.4 Hz, 0C50H), 3.90 (1H, dd, J¼2.5, 9.3 Hz, C20H), 3.99
(2H, C6 HH, C2H), 4.10 (1H, t, J¼9.3 Hz, C40H), 4.18 (1H,
dd, J¼1.5, 8.8 Hz, C4H), 4.20 (1H, d, J¼11.2 Hz,
ArCHHO), 4.30 (1H, d, J¼11.2 Hz, ArCHHO), 4.37 (1H,
t, J¼9.3 Hz, C30H), 4.43 (3H, ArCHHO£2, OCHHO), 4.64
(1H, d, J¼10.7 Hz, ArCHHO), 4.68 (1H, d, J¼2.5 Hz,
C10H), 4.71 (1H, d, J¼6.8 Hz, OCHHO), 4.89 (1H, d,
J¼10.7 Hz, ArCHHO), 5.03 (2H, d, J¼10.7 Hz,
ArCHHO£2), 6.72–6.85 (8H, aromatic protons), 6.90
(1H, d, J¼1.5 Hz, C6H), 7.15–7.31 (8H, aromatic protons),
13C NMR (C6D6, assignment of signals was not performed.)
d 26.9, 27.3, 33.1, 42.6, 54.7, 55.1, 67.6, 72.6, 72.9,
75.5, 75.9, 76.4, 77.4, 82.1, 82.2, 83.7, 83.9, 84.6,
95.7, 109.8, 109.9, 113.9, 114.1, 129.6, 130.5, 131.0
131.6, 132.7, 140.2, 149.4, 158.2, 158.3, 159.7, 159.8,
FD-MS (rel. int., %) m/z¼921 (65, [MH]þ), 920 (100, Mþ),
FD-HRMS; found: m/z 920.3458. Calcd for C49H60O13S2:
Mþ, 920.3475.
Treatment of 45 (133 mg, 141 mmol) in a similar manner
as described in Section 4.7.1 gave 46 (68.0 mg, 51%),
47 (4,5-olefin, 34.1 mg, 26%), and 48 (5,6-olefin
17.0 mg, 13%) as oils after silica gel column
chromatography.
4.19.1. Physical data for 46. IR (film) 3395, 2930, 1510,
1
1250, 1035 cm21. The H NMR spectrum of this sample
showed that it consists of the two tautomers arising from the
C1 anomeric position (isomeric ratio¼72:28). Assignments
of the signals for the main isomer and some for the minor
1
isomer are described. H NMR (C6D6, a¼0.72, b¼0.28) d
1.28 (3H£b, s, CH3 (minor)), 1.31 (3H£a, s, CH3 (major)),
1.33 (3H£b, s, CH3 (minor)), 1.36 (3H£a, s, CH3 (major)),
2.95 (1H, m, C5H or C50H), 3.15 (3H£a, s, CH3O (major)),
3.20 (3H£b, s, CH3O (minor)), 3.28 (3H£b, s, CH3O

6848
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
4.20. 5-Deoxy-6-O-[50-deoxy-20,30,40,60-O-tetrakis(4-
methoxyphenylmethyl)-50-thio-a-D-glucopyranosyl]-2-
O-methoxymethyl-5-thio-a-D-glucopyranose (a-50) and
the b-anomer (b-50)
form as an oil. [a]2D3¼þ170 (c 0.15, CHCl3), IR (film) 2955,
1
2840, 1750, 1510, 1245, 1215, 1100, 1035 cm21. The H
NMR spectrum of this sample showed that it contains small
amount of b-51 (a-51/b-51¼97:3). Assignments of the
signals for the main isomer and some for the minor isomer
1
A solution of 46 (61.5 mg, 66.6 mmol) in MeOH (3.0 mL)
was stirred with conc. HCl (5.0 mL) at room temperature for
1 h. After neutralization by addition of Et3N (100 mL), the
mixture was concentrated in vacuo. Silica gel column
chromatography of the residue (CH2Cl2/acetone¼90:10)
gave a-50 (36.5 mg, 61%) and b-50 (18.3 mg, 30%) both as
oils.
are described. H NMR (C6D6, a¼0.97, b¼0.03) d 1.50
(3H£a, s, CH3CO (major)), 1.54 (3H£b, s, CH3CO
(minor)), 1.73, (3H, s, CH3CO), 1.80 (3H£b, s, CH3CO
(minor)), 1.86 (3H£a, s, CH3CO (minor)), 3.06 (3H£a, s,
CH3O (major)), 3.07 (3H£b, s, CH3O (major)), 3.22 (1H£b,
C6HH (minor)), 3.27 (1H, m, C6HH), 3.28, 3.29, 3.30, 3.30
(each 3H, s, CH3O), 3.54 (1H, ddd, J¼2.9, 4.4,, 10.8 Hz,
C50H), 3.60 (1H, dt, J¼10.7, 3.9 Hz, C5H),0 3.66 (1H, dd,
J¼2.4, 9.7 Hz, C060HH), 3.87 (2H, C2H, C2 H), 4.07 (3H,
C40H, C6HH, C6 HH), 4.21 (1H, t, J¼9.3 Hz, C30H), 4.26
(1H, d, J¼2.9 Hz, C10H), 4.32 (3H, OCH2O, ArCHHO),
4.39 (1H, d, J¼6.9 Hz, ArCHHO), 4.46, 4.53 (each 1H, d,
J¼11.3 Hz, OCHHO), 4.68 (1H, d, J¼10.7 Hz, ArCHHO),
4.87 (1H, d, J¼10.3 Hz, ArCHHO), 5.02 (1H, d, J¼10.7 Hz,
ArCHHO), 5.06 (1H, d, J¼10.3 Hz, ArCHHO), 5.23 (1H £
b, dd, J¼8.3, 10.3 Hz, C3H (minor)), 5.61 (1H, t, J¼9.8 Hz,
C4H), 5.72 (1H£a, t, J¼9.8 Hz, C3H (major)), 6.05 (1H£b,
d, J¼8.3 Hz, C1H (minor)), 6.23 (1H£a, d, J¼2.9 Hz, C1H
(major)), 6.74–6.84 (8H, aromatic protons), 7.21 (4H,
aromatic protons), 7.32 (4H, aromatic protons), FD-MS (rel.
int., %) m/z¼1025 (17, [MþH]þ), 1024 (7.6, Mþ), 1023
(11, [M2H]þ), 903 (100, [M2(CH3OPhCH2)þH]þ), FD-
HRMS; found: m/z 1024.3593. Calcd for C52H64O17S2: Mþ,
1024.3585.
4.20.1. Physical data for a-50. [a]2D3¼þ123 (c 1.20,
MeOH), IR (film) 3430, 2930, 1510, 1250, 1100,
1
1035 cm21, H NMR (C6D6þD2O) d 3.24 (3H, s, CH3O),
3.30, 3.32, 3.33, 3.34 (each 3H, CH3O), 3.57 (1H, ddd,
J¼9.3, 2.9, 3.9 Hz, C50H), 3.66 (1H, dd, J¼2.0, 9.3 Hz,
C60HH), 3.74 (1H, dd, J¼3.9, 9.3 Hz, C6HH), 3.79–3.84
(2H, C2H, C5H), 3.87–3.93 (2H, C200H, C3H), 4.03–4.09
(2H, C40H, C60H), 4.16–4.24 (2H, C3 H, C4H), 4.28–4.32
(2H, C6HH, ArCHHO,), 4.40 (1H, d, J¼11.7 Hz,
ArCHHO), 4.45 (1H, d, J¼2.5 Hz, C10H), 4.53, 4.57 (each
1H, d, J¼11.7 Hz, ArCH2O), 4.63–4.66 (2H, OCHHO and
ArCHHO), 4.72 (1H, d, J¼6.8 Hz, OCHHO), 4.87 (1H, d,
J¼2.9 Hz, C1H), 4.98 (1H, d, J¼9.7 Hz, ArCHHO), 4.99
(1H, d, J¼9.8 Hz, ArCHHO), 5.13 (1H, d, J¼10.7 Hz,
ArCHHO), 6.77–6.85 (8H, aromatic protons), 7.16–7.42
(8H, aromatic protons), FAB-MS (negative mode, rel. int.,
%) m/z¼897 (1.6, [M2H]2), 537 (4.9, C30H33O7S2), 148
(100), FAB-HRMS (negative mode); found: m/z 897.3163.
Calcd for C46H57O14S2: [M2H]2, 897.3190.
4.20.4. 1,3,4-O-Triacetoxy-5-deoxy-6-O-[50-deoxy-
20,30,40,60-O-tetrakis(4-methoxyphenylmethyl)-50-thio-a-
D-glucopyranosyl]-2-O-methoxymethyl-5-thio-b-D-
glucopyranose (b-51). Treatment of b-50 (9.0 mg,
10 mmol) in a similar manner as described in Section
4.20.3 gave b-51 (9.0 mg, 89%) as an oil after silica gel
column chromatography. [a]2D3¼þ65.3 (c 0.10, CHCl3), IR
(film) 2925, 2860, 1750, 1510, 1245, 1215, 1100,
4.20.2. Physical data for b-50. [a]2D3¼þ93.9 (c 1.40,
MeOH), IR (film) 3450, 2910, 1610, 1510, 1250, 1100,
1
1035 cm21, H NMR (C6D6) d 2.97 (1H, m, C5H), 3.00
(3H, s, CH3O), 3.29 (6H, s, CH3O£2), 3.30, 3.31 (each 3H,
s, CH3O), 3.31 (1H, m, C6HH), 3.48 (1H, t, J¼8.3 Hz,
C3H), 3.53 (1H, ddd, J¼2.9, 4.9, 10.7 Hz, C50H), 3.60 (1H,
dd, J¼2.4, 9.7 Hz, C60HH), 3.69 (1H,0 dd, J¼6.8, 7.8 Hz,
C2H), 3.88 (1H, dd, J¼6.9, 9.3 Hz, C2 H), 3.93–4.00 (2H,
C4H, C60HH), 4.03 0(1H, dd, J¼9.3, 10.7 Hz, C40H), 4.19
(1H, t, J¼9.3 Hz, C3 H), 4.25–4.29 (2H, ArCHHO, C6HH),
4.34 (1H, d, J¼10.7 Hz, ArCHHO), 4.35 (1H, d, J¼3.4 Hz,
C10H), 4.45–4.55 (3H, OCH2O, ArCHHO), 4.64 (1H, d,
J¼10.7, ArCHHO), 4.67 (1H, d, J¼6.9 Hz, C1H), 4.93 (1H,
d, J¼10.8 Hz, ArCHHO), 5.02 (1H, d, J¼10.8 Hz,
ArCHHO), 5.06 (1H, d, J¼10.8 Hz, ArCHHO), 6.75–6.83
(8H, aromatic protons), 7.18, 7.21, 7.29, 7.35 (each br d,
J¼8.8 Hz, aromatic protons), FAB-MS (negative mode, rel.
int., %) m/z¼897 (2.1, [M2H]2), 537 (8.7, C30H33O7S2),
148 (100), FAB-HRMS (negative mode); found: m/z
897.3218. Calcd for C46H57O14S2: [M2H]2, 897.3190.
1
1035 cm21. The H NMR spectrum of this sample showed
that it contains small amount of a-51 (a-51/b-51¼9:91).
Assignments of the signals for the main isomer and some for
1
the minor isomer are described. H NMR (C6D6, a¼0.09,
b¼0.91) d 1.50 (3H£b, s, CH3CO (minor)), 1.54 (3H£a, s,
CH3CO (major)), 1.73 (3H£b, s, CH3CO (minor)), 1.74
(3H£a, s, CH3CO (major)), 1.80 (3H£a, s, CH3CO
(major)), 1.86 (3H£b, s, CH3CO (minor)), 2.72 (1H, dt,
J¼3.9 Hz, C50H), 3.07 (3H, s, CH3O), 3.22 (1H, dd, J¼3.9,
9.8 Hz, C6HH), 3.28, 3.29, 3.30, 3.30 (each 3H, s, CH3O),
3.55 (1H, ddd, J¼0 2.4, 3.9, 10.7 Hz, C50H), 3.66 (1H,0dd,
J¼2.4, 9.7 Hz, C6 HH), 3.88 (1H, dd, J¼3.0, 8.8 Hz, C2 H),
3.89 (1H, t, J¼8.3 Hz, C2H), 3.94 (1H, dd, J¼3.9, 9.8 Hz,
C60HH), 4.08 (2H, C4H, C60HH), 4.21 (1H, t, J¼8.8 Hz,
C3 H), 4.25 (1H, d, J¼3.0 Hz, C10H), 4.30 (1H, d,
J¼11.7 Hz, ArCHHO), 4.35 (1H, d, J¼11.7 Hz, ArCHHO),
4.46 (2H, s, OCH2O), 4.47 (1H, d, J¼11.2 Hz, ArCHHO),
4.56 (1H, d, J¼11.2 Hz, ArCHHO), 4.69 (1H, d, J¼10.7 Hz,
ArCHHO), 4.90 (1H, d, J¼10.3 Hz, ArCHHO), 5.04 (1H, d,
J¼10.3 Hz, ArCHHO), 5.05 (1H, d, J¼10.7 Hz, ArCHHO),
5.23 (1H£a, dd, J¼8.3, 10.3 Hz, C3H (major)), 5.56 (1H£a,
dd, 8.3, 10.3 Hz, C4H (major)), 5.61 (1H£b, t, J¼9.8 Hz,
C4H (minor)), 5.72 (1H£b, t, J¼9.8 Hz, C3H (minor)), 6.05
(1H, d, J¼8.3 Hz, C1H), 6.23 (1H£b, d, J¼2.9 Hz, C1H
(minor)), 6.74–6.83 (8H, aromatic protons), 7.20 (4H,
4.20.3. 1,3,4-O-Triacetoxy-5-deoxy-6-O-[50-deoxy-
20,30,40,60-O-tetrakis(4-methoxyphenylmethyl)-50-thio-a-
D-glucopyranosyl]-2-O-methoxymethyl-5-thio-a-D-
glucopyranose (a-51). A mixture of a-50 (30.0 mg,
33.4 mmol), Ac2O (100 mL, 1.06 mmol), and pyridine
(200 mL, 2.48 mmol) in CH2Cl2 (500 mL) was stirred at
room temperature for 33 h. After concentration in vacuo,
silica gel column chromatography of the residue (benzene/
EtOAc¼85:15) gave a-51 (28 mg, 83%) in an almost pure

J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
6849
aromatic protons), 7.32 (4H, m, aromatic protons), FD-MS
(rel. int., %) m/z¼1024 (24, Mþ), 1023 (24, [M2H]þ), 903
(100, [M2(CH3OPhCH2)þH]þ), FD-HRMS; found: m/z
1024.3566. Calcd for C52H64O17S2: Mþ, 1024.3585.
C10H), 4.53 (1H, d, J¼11.8 Hz, ArCHHO), 4,57 (1H, d,
J¼10.3 Hz, ArCHHO), 4.61 (1H, d, J¼6.9 Hz, OCHHO),
4.66 (1H, d, J¼10.3 Hz, ArCHHO), 4,69 (1H, d, J¼10.3 Hz,
ArCHHO), 4.74 (1H, d, J¼6.9 Hz, OCHHO), 4.88 (1H, dd,
J¼8.3, 9.3 Hz, C30H), 5.10 (3H, C1H, C2H, C40H), 5.36
(1H, t, J¼9.8 Hz, C4H), 6.00 (1H, t, J¼9.8 Hz, C3H), 6.67–
6.73 (9H, aromatic protons), 6.94–7.40 (14H, aromatic
protons), 7.71–7.86 (6H, aromatic protons), FD-MS (rel.
int., %) m/z¼1471 (26, [MþH]þ), 1470 (19, Mþ), 1469 (24,
[M2H]þ), 1350 (100, [M2(CH3OPhCH2)þH]þ), FD-
HRMS; found: m/z 1470.4956. Calcd for C78H86O24S2:
[M]þ, 1470.4951.
4.21. 3,4-O-Diacetoxy-5-deoxy-6-O-[50-deoxy-20,30,40,60-
O-tetrakis(4-methoxyphenylmethyl)-50-thio-a-D-gluco-
pyranosyl]-2-O-methoxymethyl-5-thio-a-D-gluco-
pyranose (a-52) and the b-anomer (b-52)
A mixture of a-51 (25.1 mg, 24.9 mmol) and hydrazine
acetate (2.8 mg, 29.0 mmol) in DMF (1.0 mL) was stirred at
room temperature for 12 h. The mixture was poured into
H2O and extracted with EtOAc. The combined extracts were
washed with brine, dried over MgSO4, and then concen-
trated in vacuo. Silica gel column chromatography of the
residue (benzene/EtOAc¼80:20) gave a-52 (19.4 mg, 79%)
and b-52 (1.9 mg, 7.8%) both as oils.
4.22. Methyl 6-O-[50-deoxy-60-O-(500-deoxy-500-thio-a-D-
glucopyranosyl)-50-thio-a-D-glucopyranosyl]-a-D-gluco-
pyranoside (a-58)
4.22.1. Removal of the MPM ethers giving methyl 6-O-
[30,40-O-diacetyl-50-deoxy-60-O-[500-deoxy-400,600-O-(4-
methoxyphenylmethylidene)-500-thio-a-D-glucopyrano-
syl]-20-O-methoxymethyl-50-thio-a-D-glucopyranosyl]-
1
4.21.1. Physical data for a-52. The H NMR spectrum
suggested that the deuterium atom was completely retained
through the reaction.
2,3,4-O-tribenzoyl-a-D-glucopyranoside
(a-56).
A
mixture of a-55 (65.1 mg, 44.2 mmol) and DDQ (50 mg,
220 mmol) in a mixture of CH2Cl2 (1.0 mL) and H2O
(100 mL) was stirred at room temperature for 1 h. The
mixture was poured into saturated aqueous NaHCO3 and
extracted with EtOAc. The combined extracts were washed
with brine, dried over MgSO4, and then concentrated in
vacuo. Silica gel column chromatography of the residue
(benzene/EtOAc¼70:30) gave a-56 (34.0 mg, 70%) as an
oil. [a]2D3¼þ176 (c 3.54, CHCl3), IR (film) 1455, 2930,
1
4.21.2. Physical data for b-52. The H NMR spectrum
suggested that the deuterium atom was completely retained
through the reaction.
4.21.3. Physical data for a-55. [a]2D3¼þ113 (c 1.35,
CHCl3), IR (film) 2930, 1730, 1510, 1245, 1100,
1030 cm21, H NMR (CDCl3) d 1.84, 1.89 (each 3H, s,
1
CH3CO), 3.04 (1H, ddd, J¼2.5, 3.9, 10.7 Hz, C500H), 3.16
(3H, s, CH3O), 3.20 (1H, dd, J¼2.9, 10.2 Hz, C60HH), 3.35
(1H, dd, J¼2.5, 9.8 Hz, C600HH), 3.41 (3H, s, CH3O), 3.44
(2H, C50H, C6HH), 3.60–3.74 (3H, C200H, C300H, C400H),
3.63, 3.66, 3.67, 3.69 (each 3H, s, CH3O), 3.80 (1H, dd,
J¼3.9, 9.8 Hz, C600HH), 3.86 (1H, dd, J¼2.4, 9.7 Hz, C20H),
3.89 (1H, dd, J¼4.4, 10.2 Hz, C60HH),004.05 (1H, dd, J¼7.3,
10.2 Hz, C6HH), 4.25–4.35 (4H, C1 H, C5H, ArCH2O),
4.36 (1H, d, J¼10.7 Hz, ArCHHO), 4.47, 4.51 (each 1H, d,
J¼11.7 Hz, ArCHHO), 4.52 (2H, s, OCH2O), 4,60 (1H, d,
J¼10.2 Hz, ArCHHO), 4.61 (1H, d, J¼2.4 Hz, C10H), 4,68
(1H, d, J¼10.7 Hz, ArCHHO), 4,73 (1H, d, J¼10.2 Hz,
ArCHHO), 5.11–5.20 (3H, C1H, C2H, C40H), 5.34 (1H, t,
J¼9.7 Hz, C30H), 5.39 (1H, t, J¼10.2 Hz, C4H), 6.05 (1H, t,
J¼10.2 Hz, C3H), 6.68–6.78 (8H, aromatic protons), 6.98–
7.40 (17H, aromatic protons), 7.74–7.87 (6H, aromatic
protons), FD-MS (rel. int., %) m/z¼1470 (12, Mþ), 1469
(18, [M2H]þ), 1350 (92, [M2(CH3OPhCH2þH)]þ), 1349
(100, [M2PhCOO]þ), FD-HRMS; found: m/z 1470.4965.
Calcd for C78H86O24S2: Mþ, 1470.4951.
1730, 1280, 1250, 1105, 1070, 1025 cm21 1H NMR
,
(C6D6þD2O) d 1.80, 1.81 (each 3H, s, CH3CO), 3.09,
3.29, 3.35 (each 3H, s, CH3O), 3.45 (1H, dd, J¼2.4,
10.2 Hz, C60HH), 3.54 (2H, C6HH, C600HH), 3.65 (1H, dt,
J¼3.9, 9.7 Hz, C005H), 3.75 (1H, 0d0 dd, J¼3.5, 4.9, 11.3 Hz,
C50H), 3.83 (1H, t, J¼9.7 Hz, C4 H), 3.93 (1H, dd, J¼2.4,
9.8 Hz, C20H), 4.02 (2H, C60HH, C200H), 4.23 (3H, C6HH,
C300H, C600HH), 4.43 (1H, d, J¼2.9 Hz, C100H), 4.43 (1H0, m,
C5H), 4.46 (2H, s, OCH2O), 4.51 (1H, d, J¼2.5 Hz, C1 H),
5.36 (1H, d, J¼3.5 Hz, C1H), 5.49 (1H, s, ArCH(OR)2),
5.58 (2H, C2H, C40H), 5.86 (2H, C30H, C4H), 6.65 (1H, t,
J¼9.8 Hz, C3H), 6.81–7.04 (11H, aromatic protons),
7.61–8.14 (8H, aromatic protons), FD-MS (rel. int., %)
m/z¼1109, (69, [MþH]þ), 1008 (100, Mþ), FD-HRMS;
found: m/z 1108.3058. Calcd for C54H66O21S2: Mþ,
1108.3069.
4.22.2. Removal of the acetyl and benzoyl groups giving
methyl 6-O-[50-deoxy-60-O-[500-deoxy-400,600-O-(4-methox-
yphenylmethylidene)-500-thio-a-D-glucopyranosyl]-20-O-
methoxymethyl-50-thio-a-D-glucopyranosyl]-a-D-gluco-
pyranoside. A mixture of the benzoate obtained in Section
4.23.1. (33.0 mg, 29.8 mmol) and NaOMe (9.6 mg,
178 mmol) in MeOH (1.0 mL) was stirred at room
temperature for 2.5 h. To the mixture DOWEX 50W-X4
(Hþ form, 10 mg) was added. After stirring for another
5 min, the mixture was filtrated and concentrated in vacuo.
Silica gel column chromatography of the residue
(EtOAc/MeOH¼80:20) gave the corresponding alcohol
4.21.4. Physical data for b-55. [a]2D7¼þ75.1 (c 0.77,
CHCl3), IR (film) 2930, 1730, 1510, 1245, 1095,
1030 cm21, H NMR (CDCl3) d 1.86, 1.94 (each 3H, s,
1
CH3CO), 3.02 (2H, C50H, C500H), 3.21 (3H, s, CH3O), 3.27
(1H, dd, J¼3.9, 9.8 Hz, C60HH), 3.31 (3H, s, CH3O), 3.33
(1H, dd, J¼2.0, 9.8 Hz, C600HH), 3.57–3.73 (5H, C200H,
C300H, C400H, C6H, C60H), 3.64, 3.65, 3.67, 3.68 (each 3H, s,
CH3O), 3.79 (2H, C20H, C600HH), 3.88 (1H, dd, J¼2.4,
11.2 Hz, C6HH), 4.08 (1H, ddd, J¼2.4, 5.8, 9.8 Hz, C5H),
4.14 (1H, d, J¼2.9 Hz, C100H), 4.27, 4.31 (each 1H, d,
J¼12.2 Hz, ArCHHO), 4.32 (1H, d, J¼10.3 Hz, ArCHHO),
4.41 (1H, d, J¼11.8 Hz, ArCHHO), 4.47 (1H, d, J¼7.8 Hz,
1
(16.7 mg, 79%) as an oil. [a]2D5¼þ258 (c 1.5, MeOH), H
NMR (CD3OD) d 3.34 (3H, s, CH3O), 3.35–3.45 (4H),
3.39, 3.42 (each 3H, s, CH3O), 3.55–3.87 (13H), 4.01 (1H,

6850
J. Fujita et al. / Tetrahedron 60 (2004) 6829–6851
dd, J¼7.8, 10.3 Hz, C60HH or C600HH), 4.11 (1H, dd,0J¼5.9,
10.7 Hz, C6HH), 4.14 (1H, dd, J¼4.4, 10.7 Hz, C6 HH or
C600HH), 4.67 (1H, d, J¼3.9 Hz, C100H), 4.71 (1H, d,
J¼2.9 Hz, C10H), 4.78 (2H, s, OCH2O), 4.81 (1H, br, C1H),
5.60 (1H, s, ArCH(OR)2), 6.90, 7.42 (each 2H, br,
J¼8.3 Hz, aromatic protons), FAB-MS (negative mode,
rel. int., %) m/z¼747 (23, [MþCl]2), 711 (30, [M2H]2),
255 (100), 148 (99), FAB-HRMS (negative mode); found:
m/z 711.1994. Calcd for C29H43O16S2: [M2H]2, 711.1993.
ddd, J¼2.4, 5.9, 9.7 Hz, C5H), 4.44 (1H, d, J¼2.5 Hz,
C100H), 4.56 (1H, d, J¼7.3 Hz, C10H), 4.61, 4.75 (each 01H,
d, J¼6.9 Hz, OCHHO), 4.91 (1H, dd, J¼8.3, 9.3 Hz, C3 H),
5.12 (2H, C1H, C2H), 5.22 (1H, t, J¼9.8 Hz, C40H), 5.39 (1H,
t. J¼9.7 Hz, C4H), 6.02 (1H, t, J¼9.7 Hz, C3H), 7.16–7.43
(9H, aromatic protons), 7.71–7.86 (6H, aromatic protons).
4.23.2. Removal of the acetyl and the benzoyl groups.
Treatment of the tetraol 57 (16.8 mg, 16.9 mmol) in a
similar manner as described in Section 4.22.2 gave the
corresponding nonanol (10.1 mg, 100%) as an oil.
4.22.3. Removal of the MOM and methoxybenzylidene
groups under acidic conditions giving a-58. A solution of
the MOM ether obtained in Section 4.22.2 (15.0 mg,
21.0 mmol) in MeOH (500 mL) was stirred with conc.
HCl (5.0 mL) at room temperature for 1 day. To the mixture
DIAION DA30 (free base form, 10 mg) was added. After
stirring for another 5 min, the mixture was filtered and
concentrated in vacuo. The residue was passed through
SepPack (ODS, MeOH/H2O¼10:90) and the eluates were
concentrated. Medium pressured column chromatography
(ODS, MeOH/H2O¼10:90) of the residue gave a-58
(9.0 mg, 78%) as an oil. [a]2D3¼þ292 (c 0.73, H2O), IR
spectrum was not measured because this sample was soluble
1
[a]2D5¼þ29.8 (c 0.75, MeOH), H NMR (CD3OD) d 3.00
(1H, ddd, J¼3.9, 7.8, 11.7 Hz, C50H00or C500H), 3.12 (1H,
ddd, J¼3.0, 7.9, 12.7 Hz, C50H or C5 H), 3.23–3.41 (3H),
3.34, 3.40 (each 3H, s, CH3O), 3.49–3.73 (8H), 3.79–3.85
(3H), 4.00 (1H, dd, J¼7.8, 9.8 Hz, C60HH or C600HH), 4.05
(1H, dd, J¼1.5, 10.7 Hz, C6HH), 4.58 (1H, d, J¼3.0 Hz,
C100H), 4.61 (1H, d, J¼8.3 Hz, C10H), 4.63 (1H, d,
J¼4.4 Hz, C1H), 4.81, 4.94 (each 1H, d, J¼6.3 Hz,
OCHHO), FD-MS (rel. int., %) m/z¼617 (100,
[MþNa]þ), FD-HRMS; found: m/z 617.1536. Calcd for
C21H38O15S2Na: [MþNa]þ, 617.1550.
1
only in H2O. H NMR (D2O) d 3.08 (1H, ddd, J¼2.9, 5.4,
4.23.3. Removal of the MOM group under acidic
conditions giving b-58. Treatment of the nonanol obtained
in Section 4.23.2. (7.0 mg, 11.8 mmol) in a similar manner
as described in Section 4.22.3 followed by also a similar
purification gave the b-58 (2.6 mg, 40%) as an oil.
[a]2D3¼275.0 (c 0.20, H2O), IR spectrum was not measured
9.3 Hz, C50H or C500H), 3.19 (1H, ddd, J¼3.0, 7.9, 10.3 Hz,
C50H or C500H), 3.34 (3H, s, CH3O), 3.41 (1H, t, J¼9.2 Hz,
C4H), 3.48 (1H, dd, J¼3.9, 9.8 Hz, C2H), 3.51–3.62 (6H,
m), 3.73–3.86 (6H, m), 3.98 (1H, dd, J¼7.9, 10.3 Hz,
C60HH or C600HH), 4.09 (1H, dd, J¼4.4, 11.2 Hz, C6HH),
4.65 (1H, d, 0 J¼3.4 Hz, C10H or C100H), 4.66 (1H, d,
J¼3.9 Hz, C1 H or C100H), 4.73 (1H, d, J¼3.9 Hz, C1H),
FAB-MS (negative mode, rel. int., %) m/z¼549 (13,
[M2H]2), 195 (27, [C6H11O5S]2), 148 (100), FAB-
HRMS (negative mode); found: m/z 549.1306. Calcd for
C19H33O14S2: [M2H]2, 549.1312.
1
because this sample was soluble only in H2O. H NMR
(D2O) d 3.19–3.25 (2H, m, C50H, C500H), 3.39 (1H, t,
J¼9.3 Hz, C30H or C300H), 3.49 (3H, s, CH3O), 3.54 (1H, t,
J¼9.8 Hz, C4H), 3.61 (1H, dd, J¼3.4, 9.8 Hz, C2H), 3.64–
3.76 (6H, m), 3.82 (1H, m, C5H), 3.89–4.01 (4H, m), 4.07–
4.15 (2H, [C6HH, C60HH] or [C6HH, C600HH]), 4.70 (1H, d,
J¼9.3 Hz, C10H), 4.80 (1H, d, J¼2.4 Hz, C100H), 4.84 (1H,
d, J¼3.4 Hz, C1H), FAB-MS (negative mode, rel. int., %)
m/z¼549 (11, [M2H]2), 195 (50, [C6H11O5S]2), 148
(100), FAB-HRMS (negative mode); found: m/z 549.1318.
Calcd for C19H33O14S2: [M2H]2, 549.1312.
4.23. Methyl 6-O-[50-deoxy-60-O-(500-deoxy-500-thio-a-D-
glucopyranosyl)-50-thio-b-D-glucopyranosyl]-a-D-
glucopyranoside (b-58)
4.23.1. Removal of the MPM ethers giving methyl 6-O-
[30,40-O-diacetyl-50-deoxy-60-O-[500-deoxy-500-thio-a-D-
glucopyranosyl]-20-O-methoxymethyl-50-thio-b-D-gluco-
pyranosyl]-2,3,4-O-tribenzoyl-a-D-glucopyranoside (57)
and its 400,600-O-(4-methoxybenzylidene)acetal (b-56).
Treatment of b-55 (40.3 mg, 27.4 mmol) with DDQ
(31 mg, 137 mmol) in a similar manner as described in
Section 4.22.1 gave benzylidene acetal b-56 (13.3 mg,
44%) and 57 (7.0 mg, 26%) as oils after silica gel column
chromatography. The methoxybenzylidene group at C400,
5. Supporting information
1H NMR spectra are given for new compounds.
Acknowledgements
00
Part of this work was supported by Grant-in-Aid for
Scientific Research (No. 12780434) from the Ministry of
Education, Science, Sports, and Culture of Japan. The
authors would like to thank Professor Jun Kawabata and Dr.
Eri Fukushi of Hokkaido University for measurements of
mass spectra. The authors are grateful to Professor Kazuo
Miyairi of Hirosaki University for fruitful discussions.
1
C6 position was cleaved during measurement of its H
NMR spectrum in CDCl3 (a signal appeared at 9.77 ppm
corresponding to the decomposed anisaldehyde and the
intensity of this signal gradually increased). Thus, the
sample (13.3 mg) was purified again by silica gel column
chromatography to give 57 (12.1 mg, 45% two steps). Thus,
the total yield of the tetraol 57 was 71%. [a]2D3¼þ114 (c
1.41, CHCl3), IR (film) 3450, 1730, 1280, 1250, 1095,
1
1025 cm21, H NMR (CDCl3) d 1.95, 1.96 (each 3H, s,
CH3CO), 3.03 (2H, C50H, C500H), 3.22 (3H, s, CH3O), 3.36
(1H, m, C60HH), 3.37 (3H, s, CH3O), 3.53–3.70 (5H, m),
3.77 (1H, dd, J¼5.7, 11.7 Hz, C600HH), 3.84 (2H, C20H,
C6HH), 3.95 (1H, dd, J¼4.8, 10.2 Hz, C60HH), 4.12 (1H,
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