Stereocontrolled glycosidations using a heterogeneous solid acid, sulfated zirconia, for the direct syntheses of α- and β-manno- and 2-deoxyglucopyranosides

Article abstract of DOI:10.1016/j.tet.2004.04.071

Novel α- and β-stereocontrolled glycosidations using a heterogeneous solid acid, sulfated zirconia (SO₄/ZrO₂), as an activator have been developed. The glycosidations of manno- and 2-deoxyglucopyranosyl α-fluorides with several alcoh

Full text of DOI:10.1016/j.tet.2004.04.071

Tetrahedron 60 (2004) 5331–5339
Stereocontrolled glycosidations using a heterogeneous solid acid,
sulfated zirconia, for the direct syntheses of a- and b-manno- and
2-deoxyglucopyranosides
†
Kazunobu Toshima, Hideyuki Nagai, Ken-ichi Kasumi, Kanako Kawahara
and Shuichi Matsumura
*
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku,
Yokohama 223-8522, Japan
Received 12 April 2004; revised 27 April 2004; accepted 28 April 2004
Abstract—Novel a- and b-stereocontrolled glycosidations using a heterogeneous solid acid, sulfated zirconia (SO4/ZrO2), as an activator
have been developed. The glycosidations of manno- and 2-deoxyglucopyranosyl a-fluorides with several alcohols using SO4/ZrO2 in MeCN
proceeded a-stereoselectively, while those with the same activator in the presence of MS 5A in Et2O occurred with b-stereoselectivity. Thus,
both the a- and b-manno- and 2-deoxyglucopyranosides were effectively obtained by the present glycosidations.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
assistance from the C2 position and the low stability of the
glycosidic bond of a 2-deoxyglycoside linkage under acidic
conditions.4 To overcome these problems, a number of
indirect methods have been developed and their high
potential demonstrated.5,6 However, it is clear that a direct
method is an ideal procedure in terms of efficiency and
practicality.7,8 In this context, stereocontrolled (not stereo-
selective) glycosidations using a solid acid as an activator
have never been reported.2 We expected that the use of a
solid acid would open a new way in the field of
stereocontrolled glycosidation. In this paper, we report
the novel stereocontrolled glycosidations of manno- and
2-deoxyglucopyranosyl a-fluorides with several alcohols
using a heterogeneous solid acid, sulfated zirconia (SO4/
ZrO2), for the direct and effective syntheses of both the
a- and b-manno- and 2-deoxyglucopyranosides (Fig. 1).9
Glycosubstances including glycoconjugates and oligo-
saccharides continue to be the central focus of research
both in chemistry and biology.1 Therefore, the development
of efficient and stereoselective glycosidation methods has
been one of the major concerns in synthetic organic
chemistry due to the structural complexity and the
biological significance of glycosubstances.2 Since a- and
b-mannopyranosides appear in many naturally occurring
bioactive substances such as asparagine-linked glyco-
proteins and certain antibiotics, the stereocontrolled for-
mation of a- and b-mannopyranosides is of considerable
importance.3 The stereoselective and direct construction of
b-mannopyranoside, however, has proved particularly
difficult to achieve, because the axial b-hydroxy group at
the C2 position and the anomeric effect blocks access to the
b-face. On the other hand, deoxy sugars are also present in
the glycosidic components of the bioactive substances.
Among them, 2-deoxyglycoside is one of the most common
and important, and found in many biologically attractive
natural products, especially in antitumor antibiotics. How-
ever, the direct and stereocontrolled glycosidation of a
2-deoxy sugar, particularly b-stereoselective glycosidation,
is also difficult due to the lack of stereodirecting anchimeric
2. Results and discussion
2.1. Stereocontrolled a- and b-mannosidations
In 1981, Paulsen reported the pioneering work on the direct
construction of the b-mannopyranoside linkage using
a-mannopyranosyl halide and silver silicate.10 In his
study, the heterogeneous silver silicate was found to activate
the a-mannopyranosyl halide and prompt a b-face attack of
the alcohol via an SN2 type pathway to exclusively produce
b-mannopyranoside. With this result in mind, we chose
several heterogeneous solid acids, montmorillonite K-10,11
Nafion-H12 and SO4/ZrO2,13 all of which show Brønsted
Keywords: Glycosidation; Sulfated zirconia; Heterogeneous solid acid;
Mannopyranoside; 2-Deoxypyranoside.
*
Corresponding author. Tel.: þ81-45-566-1576; fax: þ81-45-566-1576;
e-mail address: toshima@applc.keio.ac.jp
Taken in part from the PhD Thesis of Hideyuki Nagai, Keio University,
2004.
†
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.04.071

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K. Toshima et al. / Tetrahedron 60 (2004) 5331–5339
Figure 1. Stereocontrolled manno- and 2-deoxyglucosidations using a heterogeneous solid acid, SO4/ZrO2.
acidity and work as protic acids. These solid acids are well
known as environmentally benign catalysts in organic
synthesis because they could be easily recovered from the
reaction mixture by filtration and reused. Neutralization of
the reaction mixture is not required after the reaction was
completed. Consequently, extraction of the product from the
reaction mixture using an organic solvent is not needed in
the work-up process. As a glycosyl donor, we selected a
glycosyl fluoride. Since the proton is a hard acid and
fluoride is a hard base by the HASAB rule, we expected that
these solid acids would be effective activators of glycosyl
fluoride.14 Therefore, we first examined the glycosidations
of the totally benzylated a-mannopyranosyl fluoride 115 and
cyclohexylmethanol (3) using these solid acids. These
results are summarized in Table 1. It was found that these
glycosidations in MeCN at 25 8C for 15 h smoothly
proceeded to afford the mannopyranoside 10 in high yields.
These results clearly indicated, for the first time, that
a glycosyl fluoride was effectively activated by a solid
acid. Furthermore, SO4/ZrO2 was shown to be superior
to the others with respect to both chemical yield and
a-stereoselectivity. These results showed that the hetero-
geneous solid acid, SO4/ZrO2, was very effective for the
glycosidation of the mannopyranosyl fluoride 1. Interest-
ingly, the observed a-stereoselectivity was in sharp contrast
to the b-stereoselectivity based on Paulsen’s observation.10
Our attention next turned to the solvent effect on this novel
glycosidation. Thus, we tested the glycosidations of 1 and 3
using SO4/ZrO2 in various solvents such as MeCN, CH2Cl2,
PhMe, THF and Et2O. From the results shown in Table 2,
MeCN was found to be the best solvent to selectively obtain
the a-mannopyranoside 10a (entries 1–5 in Table 2), and
the use of 5 wt% the present activator was sufficient to
perform this reaction at 40 8C with quite satisfactory
chemical yield and a-stereoselectivity (entry 6 in Table 2).
Moreover, interestingly, the stereoselectivity of the glyco-
sidation was dramatically changed by the solvent, and a
predominant b-stereoselectivity was observed when Et2O
was used as the solvent (entry 5 in Table 2). Furthermore, it
was found that the chemical yield and the b-stereoselectivity
were slightly improved as the quantity of SO4/ZrO2
increased (entry 7 in Table 2). Finally, we found that the
use of molecular sieves 5A (MS 5A) as an additive in the
Table 2. Glycosidations of 1 and 3 by SO4/ZrO2 under several conditionsa
Table 1. Glycosidations of 1 and 3 by several solid acids in MeCNa
Entry Solvent Additive Wt% of solid acid Temp. Yield a/b Ratioc
(8C)
(%)b
1
2
3
4
5
6
7
8
MeCN None
CH2Cl2 None
20
20
20
20
20
5
25
25
25
25
25
40
25
25
93 91/9
74 69/31
Entry
Solid acid
Wt% of solid acid Yield a/b Ratioc
PhH
THF
Et2O
None
None
None
7
2
51/49
52/48
(%)b
24 34/66
99 97/3
32 24/76
99 17/83
1
2
3
Montmorillonite K-10
Nafion-H
SO4/ZrO2
20
20
20
89
92
93
76/24
89/11
91/9
MeCN None
Et2O
Et2O
None
MS 5A
100
100
a
a
b
c
All reactions were carried out by use of 2.0 equiv. of 3 to 1.
Isolated yields after purification by column chromatography.
All reactions were carried out using 2.0 equiv. of 3 to 1.
b
c
Isolated yields after purification by column chromatography.
a:b Ratios were determined by 1H NMR (270 MHz) spectroscopy and/or
isolation of pure isomers.
a:b Ratios were determined by 1H NMR (270 MHz) spectroscopy and/or
isolation of pure isomers.

K. Toshima et al. / Tetrahedron 60 (2004) 5331–5339
5333
glycosidation using Et2O led to not only a high chemical
yield but also to a good stereoselectivity for the b-manno-
pyranoside 10b (entry 8 in Table 2). In addition, it was
confirmed that MS 5A was shown to be superior to the other
MSs such as MS 3A and MS 4A probably due to the acidic
property of MS 5A and the basic nature of MS 3A and
MS 4A.14 Thus, the glycosidation of 1 and 3 using 5 wt%
SO4/ZrO2 in MeCN at 40 8C for 15 h exclusively gave the
a-mannopyranoside 10a, while the glycosidation employ-
ing 100 wt% the same activator in the presence of equal
amounts of MS 5A in Et2O at 25 8C for 15 h afforded the
b-mannopyranoside 10b in high yield with good stereo-
selectivity. To enhance the synthetic utility of this novel and
unusual reaction, the glycosidations using other primary and
secondary alcohols 4–9 including sugar derivatives were
next examined. Based on the results summarized in Table 3,
all glycosidations of 1 and 4–9 using 5 wt% SO4/ZrO2 in
MeCN at 40 8C for 15 h, as well as that of 3, effectively
proceeded to give the corresponding a-mannopyranosides
11a–16a, respectively, in high yields with high stereo-
selectivities. On the other hand, the stereoselective synth-
eses of the corresponding b-mannopyranosides by the
present glycosidation are outlined in Table 4. It was found
that 200 wt% SO4/ZrO2 and 200 wt% MS 5A were required
for the glycosidations of the sugar derivative alcohols 7–9
(entries 5–7 in Table 4). Although only b-mannopyranoside
15b was produced in moderate yield with low stereo-
selectivity due to the low reactivity of 8 (entry 6 in Table 4),
other b-mannopyranosides 11b–14b and 16b were
obtained in good to high yields with good stereoselectivities
by the glycosidations of 1 with 4–7 and 9 under conditions
similar to that for 10b. The anomeric configurations of the
obtained mannopyranosides were determined by compari-
son with authentic samples, which were obtained by the
1
previous procedures,5,7 with the aid of H NMR analysis.
2.2. Stereocontrolled a- and b-2-deoxyglucosidations
Based on the results for the stereocontrolled a- and
b-mannosidations, we tried to apply the present glyco-
sidation method to the stereocontrolled synthesis of
2-deoxyglycosides. Thus, the glycosidations of the benzyl-
ated 2-deoxy-a-glucopyranosyl fluoride 216 and 3 using
SO4/ZrO2 with or without MS 5A were examined under
several conditions. These results are summarized in Table 5.
It was found that the glycosidation of 2 and 3 using 5 wt% of
SO4/ZrO2 in MeCN at 25 8C for 1 h smoothly proceeded to
afford the corresponding 2-deoxyglucopyranoside 17 in
high yield with high a-stereoselectivity (entry 2 in Table 5).
Both the chemical yield and a-stereoselectivity decreased as
the reaction temperature increased (entry 1 in Table 5).
Moreover, the stereoselectivity of the glycosidation was
dramatically changed by the solvent as observed in the
glycosidation of 1, and the corresponding 2-deoxy-b-
glucopyranoside 17b was predominantly produced when
Et2O was used as the solvent. Furthermore, it was found that
the b-stereoselectivity was highly dependent on the reaction
temperature and the amount of MS 5A (entries 3–8 in
Table 5); the use of 500 wt% MS 5A as an additive along
with 100 wt% SO4/ZrO2 in Et2O at 0 8C led to the highest
chemical yield and stereoselectivity for the 2-deoxy-b-
glucopyranoside 17b (entry 7 in Table 5). Thus, the
glycosidation of 2 and 3 using 5 wt% SO4/ZrO2 in MeCN
at 25 8C for 1 h predominantly gave the corresponding
2-deoxy-a-glucopyranoside 17a, while the glycosidation
employing 100 wt% of the same activator in the presence of
five times the amount of MS 5A in Et2O at 0 8C for 1 h
afforded the corresponding 2-deoxy-b-glucopyranoside 17b
in high yield with good stereoselectivity. It is noteworthy
that these optimized conditions for selectively obtaining
both the 2-deoxy-a- and b-glycosides including the reaction
temperature and time, and the ratio of SO4/ZrO2 and MS 5A
significantly differed from those for the previously men-
tioned stereocontrolled mannosidations due to the higher
reactivity of the 2-deoxyglycosyl donor 2 compared to that
of the mannosyl donor 1. With these optimized conditions in
hand, the glycosidations using other primary and secondary
alcohols 4–9 were next carried out to examine the scope and
limitation of this glycosidation. Based on the results
summarized in Table 6, the glycosidations of 2 with 4–7
and 9 using 5 wt% SO4/ZrO2 in MeCN at 25 8C for 1 h, as
well as that of 3, effectively proceeded to afford the
corresponding 2-deoxy-a-glucopyranosides 18a–21a and
23a, respectively, in high yields with good stereoselectiv-
ities. Unfortunately, when the less reactive alcohol 8 was
employed as the acceptor, a moderate yield of 22a, which
was contaminated with a considerable amount of the
Table 3. a-Stereoselective glycosidations of 1 and several alcoholsa
Entry
Alcohol
Product
Yield (%)b
a/b Ratioc
1
2
3
4
5
6
7
3
4
5
6
7
8
9
10
11
12
13
14
15
16
99
97
96
96
88
75
84
97/3
98/2
98/2
97/3
97/3
98/2
97/3
a
All reactions were carried out using 2.0 equiv. of the alcohol to 1.
Isolated yields after purification by column chromatography.
a:b Ratios were determined by 1H NMR (270 MHz) spectroscopy and/or
isolation of pure isomers.
b
c
Table 4. b-Stereoselective glycosidations of 1 and several alcoholsa
Entry
Alcohol
Product
Yield (%)b
a/b Ratioc
1
2
3
4
3
4
5
6
7
8
9
10
11
12
13
14
15
16
99
96
97
95
84
55
80
17/83
20/80
19/81
16/84
27/73
56/44
21/79
5d
6d
7d
a
All reactions were carried out using 2.0 equiv. of the alcohol to 1.
Isolated yields after purification by column chromatography.
a:b Ratios were determined by 1H NMR (270 MHz) spectroscopy and/or
isolation of pure isomers.
This reaction was carried out by use of SO4/ZrO2 (200 wt%) and MS 5A
(200 wt%) to 1.
b
c
d

5334
K. Toshima et al. / Tetrahedron 60 (2004) 5331–5339
Table 5. Glycosidations of 2 and 3 by SO4/ZrO2 under several conditionsa
Entry
Solvent
Wt% of SO4/ZO2
Wt% of MS 5A
Temp. (8C)
Yield (%)b
a/b Ratioc
1
2
3
4
5
6
7
8
MeCN
MeCN
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
5
5
0
0
45
25
25
0
0
0
74
98
90
98
97
98
98
96
85/15
88/12
50/50
24/76
25/75
21/79
19/81
18/82
100
100
100
100
100
100
100
100
200
300
500
1000
0
0
a
All reactions were carried out using 2.0 equiv. of 3 to 2.
Isolated yields after purification by column chromatography.
a:b Ratios were determined by 1H NMR (270 MHz) spectroscopy and/or isolation of pure isomers.
b
c
corresponding 2,3-unsaturated glycoside, was obtained
(entry 6 in Table 6). The 2,3-unsaturated glycoside was
probably produced by the Ferrier reaction17 of the glycal 24,
which came from 2 by treatment with SO4/ZrO2, and the
alcohol as shown in Figure 2. On the other hand, the
stereoselective syntheses of the corresponding 2-deoxy-b-
glucopyranosides 18b–23b by the present glycosidation are
outlined in Table 7. As observed for the a-stereoselective
glycosidation, in the case of 8 and 9, moderate yields and
stereoselectivities were observed, and considerable amounts
of the corresponding 2,3-unsaturated glycosides were
produced (entries 6 and 7 in Table 7). However, the other
2-deoxy-b-glucopyranosides 18b–21b were obtained in
good to high yield with good stereoselectivities by the
glycosidations of 2 and 4–7 as well as that of 3. It was also
confirmed that no epimerization of the formed b-glycoside
bond was observed during the reaction. Comparing the two
types of glycosidations, the mannosidation was more
effectively performed rather than the 2-deoxyglucosidation
by the present method because the formation of
2,3-unsaturated glycosides did not occur as a side reaction
during the glycosidation of mannosyl fluoride 1 even when a
low reactive alcohol was used as an acceptor.
Table 7. b-Stereoselective glycosidations of 2 and several alcoholsa
Table 6. a-Stereoselective glycosidations of 2 and several alcoholsa
Entry
Alcohol
Product
Yield (%)b
a/b Ratioc
1
2
3
4
5
6
7
3
4
5
6
7
8
9
17
18
19
20
21
22
23
98
96
99
97
81
50
56
19/81
15/85
19/81
20/80
28/72
30/70
33/67
Entry
Alcohol
Product
Yield (%)b
a/b Ratioc
1
2
3
4
5
6
7
3
4
5
6
7
8
9
17
18
19
20
21
22
23
98
92
97
92
82
53
80
88/12
84/16
82/18
83/17
86/14
88/12
80/20
a
All reactions were carried out using 2.0 equiv. of the alcohol to 2.
Isolated yields after purification by column chromatography.
a:b Ratios were determined by 1H NMR (270 MHz) spectroscopy and/or
isolation of pure isomers.
b
c
a
All reactions were carried out using 2.0 equiv. of the alcohol to 2.
Isolated yields after purification by column chromatography.
a:b Ratios were determined by 1H NMR (270 MHz) spectroscopy and/or
isolation of pure isomers.
2.3. Mechanistic considerations
b
c
To investigate the mechanism of the present unusual
stereocontrolled glycosidations, we examined the effect of
the leaving group of the glycosyl donor and its stereo-
chemistry. For this purpose, we prepared another glycosyl
donor, mannopyranosyl sulfoxide 25,9c possessing a
b-configuration at the C1 position, and then examined the
glycosidation with 3 under similar conditions employed for
the glycosyl donor 1. As shown in Figure 3, it was found that
when the glycosidation was performed using SO4/ZrO2 in
MeCN, the a-mannopyranoside 17a (94%, a/b¼90/10)
was selectively obtained, while that with the same activator
in the presence of MS 5A in Et2O predominantly afforded
the b-mannopyranoside 17b (99%, a/b¼19/81). These
results showed exactly the same tendency as observed in the
glycosidations using a-mannopyranosyl fluoride 1. From
Figure 2. 2,3-Unsaturated glycoside formation in the glycosidation of 2.

K. Toshima et al. / Tetrahedron 60 (2004) 5331–5339
5335
Figure 3. Mannosidations of mannosyl sulfoxide using a heterogeneous solid acid, SO4/ZrO2.
Figure 4. Presumed mechanism of the stereocontrolled glycosidation using SO4/ZrO2.
these results, it was clarified that the a- and b-stereoselectiv-
ities of the present glycosidations are completely independent
of both the kind of leaving group at the anomeric position of
the glycosyl donor and its configuration. Therefore, these
glycosidations proceeds via an SN1 type reaction and involves
the oxonium intermediate A as indicated in Figure 4. When
MeCNisusedasa solvent, thealcohol attacksthea-faceofthe
anomeric center of the oxonium intermediate A due to the
steric interaction of the axial b-hydroxy group at the C2
position and the anomeric effect to generate the a-glycosidic
bond (path a in Fig. 4). It is known, in some cases, that MeCN
is coordinated with the a-face of the anomeric center of the
oxonium intermediate, and then the alcohol attacks the b-face
of the oxonium intermediate.18 However, in the present case,
MeCN is probably coordinated to Zr on SO4/ZrO2 rather than
the oxonium intermediate A on the surface of SO4/ZrO2.
Therefore, the solvent effect of MeCN producing the
b-stereoselectivity was not observed. On the other hand, when
Et2O was used as the solvent, Et2O could coordinate with both
Zr on SO4/ZrO2 and the a-face of the oxonium intermediate A
due to the bidentate coordinating nature of Et2O. Therefore,
SO4/ZrO2 coordinates with the a-face of the oxonium
intermediate A through Et2O. Consequently, an alcohol
attacks the less hindered b-face of the oxonium intermediate
A to form the b-glycosidic bond. In this case, MS 5A would
play an important role to replace H2O, originally coordinated
with Zr on SO4/ZrO2, with Et2O, and increase the Et2O
coordinated points on the surface of SO4/ZrO2.
for the direct syntheses of both the a- and b-manno- and
2-deoxyglucopyranosides from manno- and 2-doxygluco-
pyranosyl fluorides and alcohols using a hetero-
geneous solid acid. Furthermore, the results including
the simple protocol and stereoselectivity should be
instructive for further research that employs hetero-
geneous solid acids in glycosidation reactions. More-
over, the protocols should find wide application for the
synthesis of biologically important natural products and
functional materials.
4. Experimental
4.1. General methods
Melting points were determined on a micro hot-stage
Yanako MP-S3 and were uncorrected. Optical rotations
were measured on a JASCO DIP-360 photoelectric
polarimeter in chloroform unless otherwise noted. 1H
NMR spectra were recorded on a JEOL GSX 270
(270 MHz) or a Lambda 300 (300 MHz) in CDCl3
using TMS as internal standard unless otherwise noted.
Silica gel TLC and column chromatography were
performed on Merck TLC 60F-254 (0.25 mm) and
Kanto Chemical Co., Inc Silica Gel 60 N (spherical,
neutral), respectively. Air- and/or moisture-sensitive
reactions were carried out under an atmosphere of
argon with oven-dried glassware. In general, organic
solvents were purified and dried by the appropriate
procedure, and evaporation and concentration were
carried out under reduced pressure below 30 8C, unless
otherwise noted.
3. Conclusion
We have presented a novel and stereocontrolled strategy

5336
K. Toshima et al. / Tetrahedron 60 (2004) 5331–5339
4.2. Glycosidation protocols for the preparations of the
a- and b-mannopyranosides
(2H, s), 4.66 (1H, d, J¼12.0 Hz), 4.70 (1H, d, J¼12.4 Hz),
4.76 (1H, d, J¼12.4 Hz), 4.84–4.89 (2H, m), 7.14–7.40
(20H, m). Anal. Calcd for C42H52O6: C, 77.27; H, 8.03.
Found: C, 77.22; H, 7.82
a-Mannopyranosides: to a stirred solution of the glycosyl
fluoride 1 (0.5 mmol) and a glycosyl acceptor (1.0 mmol) in
dry MeCN (5.0 ml) was added SO4/ZrO2 (5 wt% to the
glycosyl donor 1). After stirring for 15 h at 40 8C, the
mixture was filtered and the filtrate was concentrated in
vacuo. Purification of the residue by flash column
chromatography gave mannopyranosides which predomin-
ately contained its a-anomer. b-Mannopyranosides: to a
stirred solution of 1 (0.5 mmol) and a glycosyl acceptor
(1.0 mmol) in dry Et2O (5.0 ml) were added powdered MS
5A (100 wt% to 1) and SO4/ZrO2 (100 wt% to 1). After
stirring for 15 h at 25 8C, the similar workup and
purification mentioned above gave mannopyranosides,
which included its b-anomer as a major product.
4.3.4. n-Octyl 2,3,4,6-tetra-O-benzyl-b-D-mannopyrano-
side (11b). White solid. Rf 0.55 (4/1 n-hexane/EtOAc);
[a]2D7 254.88 (c 0.44, CHCl3); mp 35.5–37.0 8C; 1H NMR d
0.88 (1H, t, J¼6.4 Hz), 1.21–1.43 (10H, m), 1.56–1.70
(2H, m), 3.36–3.52 (3H, m), 3.70–3.90 (4H, m), 3.98 (1H,
dt, J¼9.2, 6.4 Hz), 4.36 (1H, br s), 4.42 (1H, d, J¼11.2 Hz),
4.50 (1H, d, J¼11.2 Hz), 4.53 (1H, d, J¼10.4 Hz), 4.58 (1H,
d, J¼12.4 Hz), 4.68 (1H, d, J¼12.4 Hz), 4.87 (1H, d,
J¼12.4 Hz), 4.90 (1H, d, J¼10.4 Hz), 4.99 (1H, d,
J¼12.4 Hz), 7.15–7.50 (20H, m). Anal. Calcd for
C42H52O6: C, 77.27; H, 8.03. Found: C, 77.20; H, 7.95.
4.3.5. Isopropyl 2,3,4,6-tetra-O-benzyl-a-D-manno-
pyranoside (12a). White solid. Rf 0.49 (100/1 chloroform/
EtOAc); [a]2D9 þ39.58 (c 0.50, CHCl3); mp 65.0–66.0 8C;
1H NMR d 1.06 (3H, d, J¼6.0 Hz), 1.16 (3H, d, J¼6.0 Hz),
3.67–4.04 (7H, m), 4.50 (1H, d, J¼10.8 Hz), 4.57 (1H, d,
J¼12.0 Hz), 4.64 (2H, s), 4.67 (1H, d, J¼12.0 Hz), 4.70
(1H, d, J¼12.0 Hz), 4.78 (1H, d, J¼10.8 Hz), 4.95 (1H, d,
J¼1.6 Hz), 7.13–7.40 (20H, m). Anal. Calcd for C37H42O6:
C, 76.26; H, 7.26. Found: C, 76.14; H, 7.05.
4.3. Glycosidation protocols for the preparations of the
2-deoxy-a- and b-glucopyranosides
2-Deoxy-a-glucopyranosides: to a stirred solution of the
glycosyl fluoride 2 (0.5 mmol) and an alcohol (1.0 mmol) in
dry MeCN (5.0 ml) was added SO4/ZrO2 (5 wt% to the
glycosyl donor 2). After stirring for 1 h at 25 8C, the mixture
was filtered and the filtrate was concentrated in vacuo.
Purification of the residue by flash column chromatography
gave the 2-deoxyglucopyranosides which predominantly
contained the a-anomer. 2-Deoxy-b-glucopyranosides: To
a stirred solution of 2 (0.5 mmol) and an alcohol (1.0 mmol)
in dry Et2O (5.0 ml) were added powdered MS 5A
(500 wt% to 2) and SO4/ZrO2 (100 wt% to 2). After stirring
for 1 h at 0 8C, a similar workup and purification as that
mentioned above gave the 2-deoxyglucopyranosides which
selectively included the b-anomer.
4.3.6. Isopropyl 2,3,4,6-tetra-O-benzyl-b-D-mannopyra-
noside (12b). White solid. Rf 0.25 (100/1 chloroform/
EtOAc); [a]2D8 270.48 (c 0.49, CHCl3); mp 82.5–84.0 8C;
1H NMR d 1.16 (3H, d, J¼6.0 Hz), 1.30 (3H, d, J¼6.0 Hz),
3.43 (1H, ddd, J¼8.4, 6.0, 2.4 Hz), 3.50 (1H, dd, J¼9.6,
3.6 Hz), 3.69–3.88 (4H, m), 4.02 (1H, septet, J¼6.0 Hz),
4.43 (1H, d, J¼12.4 Hz), 4.46 (1H, br s), 4.50 (1H, d,
J¼12.4 Hz), 4.53 (1H, d, J¼10.8 Hz), 4.57 (1H, d, J ¼
11.6 Hz), 4.63 (1H, d, J¼11.6 Hz), 4.90 (1H, d, J¼10.8 Hz),
4.98 (1H, d, J¼12.0 Hz), 5.00 (1H, d, J¼12.0 Hz), 7.16–
7.50 (20H, m). Anal. Calcd for C37H42O6: C, 76.26; H, 7.26.
Found: C, 76.21; H, 7.07.
4.3.1. Cyclohexylmethyl 2,3,4,6-tetra-O-benzyl-a-D-
mannopyranoside (10a). Colorless syrup. Rf 0.60 (4/1
n-hexane/EtOAc); [a]2D8 þ37.88 (c 0.94, CHCl3); 1H NMR d
0.80–1.74 (11H, m), 3.15 (1H, dd, J¼9.6, 6.0 Hz), 3.45
(1H, dd, J¼9.6, 7.2 Hz), 3.68–3.81 (4H, m), 3.86–4.01
(2H, m), 4.48–4.79 (7H, m), 4.82 (1H, d, J¼2.0 Hz), 4.87
(1H, d, J¼10.4 Hz), 7.14–7.39 (20H, m). Anal. Calcd for
C41H48O6: C, 77.33; H, 7.60. Found: C, 77.27; H, 7.62.
4.3.7. Cyclohexyl 2,3,4,6-tetra-O-benzyl-a-D-manno-
pyranoside (13a). Colorless syrup. Rf 0.40 (100/1 chloro-
1
form/EtOAc); [a]2D8 þ44.78 (c 0.78, CHCl3); H NMR d
1.09–1.88 (10H, m), 3.51–3.62 (1H, m), 3.65–4.02 (6H,
m), 4.50 (1H, d, J¼10.8 Hz), 4.53 (1H, d, J¼12.4 Hz), 4.63
(2H, s), 4.66 (1H, d, J¼12.4 Hz), 4.69 (1H, d, J¼12.4 Hz),
4.76 (1H, d, J¼12.4 Hz), 4.87 (1H, d, J¼10.8 Hz), 4.98 (1H,
d, J¼1.6 Hz), 7.13–7.39 (20H, m). Anal. Calcd for
C40H46O6: C, 77.14; H, 7.44. Found: C, 77.06; H, 7.31.
4.3.2. Cyclohexylmethyl 2,3,4,6-tetra-O-benzyl-b-D-
mannopyranoside (10b). White solid. Rf 0.60 (4/1
n-hexane/EtOAc); [a]D28 252.98 (c 0.69, CHCl3); mp 64.5–
1
66.0 8C; H NMR d 0.83–1.87 (11H, m), 3.20 (1H, dd,
J¼8.8, 6.4 Hz), 3.44 (1H, ddd, J¼7.6, 6.0, 2.0 Hz), 3.51
(1H, dd, J¼8.8, 2.8 Hz), 3.71–3.92 (5H, m), 4.35 (1H, br s),
4.42(1H, d, J¼12.0 Hz), 4.50(1H, d,J¼12.0 Hz), 4.53(1H, d,
J¼10.8 Hz), 4.59 (1H, d, J¼12.4 Hz), 4.64 (1H, d, J ¼
12.4 Hz), 4.87 (1H, d, J¼13.2 Hz), 4.91 (1H, d, J¼10.8 Hz),
5.00 (1H, d, J¼13.2 Hz), 7.16–7.49 (20H, m). Anal. Calcd for
C41H48O6: C, 77.33; H, 7.60. Found: C, 77.31; H, 7.48.
4.3.8. Cyclohexyl 2,3,4,6-tetra-O-benzyl-b-D-manno-
pyranoside (13b). White solid. Rf 0.30 (100/1 chloroform/
EtOAc); [a]2D8 260.98 (c 0.38, CHCl3); mp 87.5–89.0 8C;
1H NMR d 1.73–2.03 (10H, m), 3.40–3.52 (2H, m), 3.67–
3.88 (5H, m), 4.42 (1H, d, J¼12.0 Hz), 4.50 (1H, br s), 4.50
(1H, J¼12.0 Hz), 4.55 (1H, d, J¼10.4 Hz), 4.58 (1H, d,
J¼12.0 Hz), 4.64 (1H, d, J¼12.0 Hz), 4.90 (1H, d, J ¼
12.4 Hz), 4.90 (1H, d, J¼10.4 Hz), 5.01 (1H, d, J¼12.4 Hz),
7.17–7.50 (20H, m). Anal. Calcd for C40H46O6: C, 77.14;
H, 7.44. Found: C, 77.07; H, 7.29.
4.3.3. n-Octyl 2,3,4,6-tetra-O-benzyl-a-D-mannopyrano-
side (11a). Colorless syrup. Rf 0.55 (4/1 n-hexane/EtOAc);
[a]2D8 þ31.98 (c 0.82, CHCl3); 1H NMR d 0.90 (1H, t,
J¼6.4 Hz), 1.21–1.34 (10H, m), 1.48–1.57 (2H, m), 3.34
(1H, dt, J¼9.6, 6.4 Hz), 3.60–3.79 (5H, m), 3.87–4.02 (2H,
m), 4.50 (1H, d, J¼10.8 Hz), 4.54 (1H, d, J¼12.0 Hz), 4.63
4.3.9. Methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-
benzyl-a-D-mannopyranosyl)-a-D-glucopyranoside

K. Toshima et al. / Tetrahedron 60 (2004) 5331–5339
5337
(14a). Colorless syrup. Rf 0.30 (6/1 toluene/EtOAc); [a]D28
þ44.58 (c 0.54, CHCl3); 1H NMR d 3.33 (3H, s), 3.44 (1H,
dd, J¼9.0, 3.0 Hz), 3.54–3.73 (5H, m), 3.78 (1H, dd, J¼3.0,
1.0 Hz), 3.79–3.87 (2H, m), 3.91 (1H, dd, J¼9.0, 8.8 Hz),
3.99 (1H, dd, J¼9.0, 8.8 Hz), 4.43 (1H, d, J¼12.0 Hz), 4.48
(1H, d, J¼10.8 Hz), 4.55 (1H, d, J¼3.2 Hz), 4.60 (1H, d,
J¼12.0 Hz), 4.61 (2H, s), 4.67 (1H, d, J¼12.0 Hz), 4.68
(1H, d, J¼12.2 Hz), 4.73 (1H, d, J¼12.2 Hz), 4.78 (1H,
d, J¼12.0 Hz), 4.79 (1H, d, J¼10.2 Hz), 4.85 (1H, d,
J¼10.8 Hz), 4.87 (1H, d, J¼10.8 Hz), 4.96 (1H, d,
J¼1.0 Hz) 4.97 (1H, d, J¼10.2 Hz), 7.10–7.39 (35H, m).
Anal. Calcd for C62H66O11: C, 75.43; H, 6.74. Found: C,
75.28; H, 6.43.
7.40 (25H, m). Anal. Calcd for C47H49N3O9: C, 70.57; H,
6.17; N, 5.25. Found: C, 70.55; H, 6.23; N, 5.13.
4.3.14. 1,6-Anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-
(2,3,4,6-tetra-O-benzyl-b-D-mannopyranosyl)-b-D-
glucopyranose (16b). Colorless syrup. Rf 0.40 (4/1 toluene/
EtOAc); [a]2D7 236.58 (c 1.21, CHCl3); 1H NMR d 3.25 (1H,
br s), 3.47 (1H, ddd, J¼9.6, 6.0, 2.4 Hz), 3.54 (1H, dd,
J¼9.6, 2.8 Hz), 3.69–3.78 (3H, m), 3.80 (1H, dd, J¼0.8,
0.8 Hz), 3.88 (1H, dd, J¼9.6, 9.6 Hz), 3.96 (1H, br s, H-4),
4.03 (1H, d, J¼2.8 Hz), 4.08–4.18 (1H, m), 4.43–4.69 (9H,
m), 4.86–5.04 (3H, m), 5.52 (1H, br s), 7.18–7.44 (25H, m).
Anal. Calcd for C47H49N3O9: C, 70.57; H, 6.17; N, 5.25.
Found: C, 70.48; H, 6.23; N, 5.16.
4.3.10. Methyl 2,3,4-tri-O-benzyl-6-O-(2,3,4,6-tetra-O-
benzyl-b-D-mannopyranosyl)-a-D-glucopyranoside
(14b). White solid. Rf 0.28 (6/1 toluene/EtOAc); [a]D28
4.3.15. Cyclohexylmethyl 3,4,6-tri-O-benzyl-2-deoxy-a-
D-arabino-hexopyranoside (17a). Colorless syrup. Rf 0.36
(5/2 n-hexane/ether); [a]2D9 þ67.08 (c 0.88, CHCl3); 1H
NMR d 0.81–1.02 (2H, m), 1.05–1.35 (3H, m), 1.46–1.81
(7H, m), 2.27 (1H, br dd, J¼12.4, 4.8 Hz), 3.15 (1H, dd,
J¼9.2, 6.0 Hz), 3.41 (1H, dd, J¼9.2, 6.8 Hz), 3.56– 3.83
(4H, m), 3.98 (1H, ddd, J¼11.2, 8.4, 4.8 Hz), 4.51 (2H, d,
J¼11.0 Hz), 4.64 (1H, d, J¼11.0 Hz), 4.65 (1H, d, J ¼
11.0 Hz), 4.68 (1H, d, J¼11.0 Hz), 4.89 (1H, d, J¼11.0 Hz),
4.91 (1H, br d, J¼3.2 Hz), 7.14–7.20 (2H, m), 7.22–7.39
(13H, m). Anal. Calcd for C34H42O5: C, 76.95; H, 7.98.
Found: C, 76.93; H, 7.97.
1
215.88 (c 1.04, CHCl3); mp 122–123 8C; H NMR d 3.32
(3H, s), 3.34–3.50 (4H, m), 3.50 (1H, dd, J¼9.2, 3.0 Hz),
3.66–3.88 (5H, m), 4.01 (1H, dd, J¼9.0, 9.0 Hz), 4.11 (1H,
br s), 4.16 (1H, dd, J¼10.0, 1.2 Hz), 4.47 (1H, d, J ¼
11.8 Hz), 4.51 (1H, d, J¼11.0 Hz), 4.52 (1H, d, J¼11.8 Hz),
4.49–4.55 (1H, m), 4.57 (1H, br s), 4.57 (2H, s), 4.66 (1H, d,
J¼11.6 Hz), 4.78 (1H, d, J¼11.6 Hz), 4.81 (1H, d,
J¼11.0 Hz), 4.82 (1H, d, J¼12.0 Hz), 4.83 (1H, d, J ¼
3.2 Hz), 4.88 (1H, d, J¼10.8 Hz), 4.93 (1H, d, J¼12.0 Hz),
5.01 (1H, d, J¼10.8 Hz), 7.14–7.44 (35H, m). Anal. Calcd
for C62H66O11: C, 75.43; H, 6.74. Found: C, 75.09; H, 6.55.
4.3.16. Cyclohexylmethyl 3,4,6-tri-O-benzyl-2-deoxy-b-
D-arabino-hexopyranoside (17b). White solid. Rf 0.45 (5/2
n-hexane/ether); [a]D28 218.58 (c 1.32, CHCl3); mp 72.0–
73.0 8C; 1H NMR d 0.82–1.02 (2H, m), 1.07–1.34 (3H, m),
1.50–1.84 (7H, m), 2.35 (1H, ddd, J¼12.4, 4.8, 1.6 Hz),
3.22 (1H, dd, J¼9.0, 6.4 Hz), 3.40 (1H, ddd, J¼9.2, 4.4,
1.6 Hz), 3.49 (1H, dd, J¼9.2, 8.0 Hz), 3.65 (1H, dd, J¼11.0,
4.4 Hz), 3.69 (1H, ddd, J¼12.0, 8.0, 4.8 Hz), 3.73 (1H, dd,
J¼9.0, 6.0 Hz), 3.77 (1H, dd, J¼11.0, 1.6 Hz), 4.40 (1H, dd,
J¼9.6, 1.6 Hz), 4.55 (1H, d, J¼10.8 Hz), 4.57 (1H, d,
J¼11.6 Hz), 4.59 (1H, d, J¼12.4 Hz), 4.63 (1H, d, J ¼
12.4 Hz), 4.69 (1H, d, J¼11.6 Hz), 4.90 (1H, d, J¼10.8 Hz),
7.17–7.23 (2H, m), 7.23–7.38 (13H, m). Anal. Calcd for
C34H42O5: C, 76.95; H, 7.98. Found: C, 76.97; H, 7.62.
4.3.11. Methyl 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-a-D-mannopyranosyl)-a-D-glucopyranoside
(15a). Colorless syrup. Rf 0.41 (2/1 n-hexane/EtOAc); [a]D28
þ17.78 (c 1.31, CHCl3); 1H NMR d 3.39 (3H, s), 3.50–3.60
(2H, m), 3.61–3.89 (9H, m), 3.97 (1H, dd, J¼9.0, 9.0 Hz),
4.10 (1H, d, J¼11.8 Hz), 4.21 (1H, d, J¼11.8 Hz), 4.42 (1H,
d, J¼12.0 Hz), 4.42 (1H, d, J¼11.4 Hz), 4.48 (1H, d,
J¼10.6 Hz), 4.52–4.64 (7H, m), 4.67 (1H, d, J¼12.0 Hz),
4.83 (1H, d, J¼10.8 Hz), 5.08 (1H, d, J¼11.2 Hz), 5.29 (1H,
d, J¼1.2 Hz), 7.11–7.32 (35H, m). Anal. Calcd for
C62H66O11: C, 75.43; H, 6.74. Found: C, 75.16; H, 6.78.
4.3.12. Methyl 2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-
benzyl-b-D-mannopyranosyl)-a-D-glucopyranoside
(15b). Colorless syrup. Rf 0.32 (2/1 n-hexane/EtOAc); [a]D28
4.3.17. n-Octyl 3,4,6-tri-O-benzyl-2-deoxy-a-D-arabino-
hexopyranoside (18a). Colorless syrup. Rf 0.36 (5/2
1
220.78 (c 1.19, CHCl3); H NMR d 3.24–3.32 (1H, m),
1
3.28 (1H, dd, J¼9.0, 2.6 Hz), 3.37 (3H, s), 3.43–3.59 (4H,
m), 3.64–3.77 (3H, m), 3.87 (1H, dd, J¼9.0, 9.0 Hz), 3.91
(1H, dd, J¼6.6, 2.0 Hz), 3.88–3.95 (1H, m), 4.36 (1H, d,
J¼11.8 Hz), 4.37 (1H, d, J¼11.8 Hz), 4.40 (1H, d,
J¼12.0 Hz), 4.42 (1H, br s), 4.45–4.53 (3H, m), 4.57 (1H,
d, J¼3.0 Hz), 4.57 (1H, d, J¼12.0 Hz), 4.59 (1H, d,
J¼11.8 Hz), 4.75 (1H, d, J¼11.0 Hz), 4.77 (1H, d,
J¼11.8 Hz), 4.81–4.88 (1H, m), 4.83 (2H, s), 5.15 (1H,
d, J¼11.0 Hz), 7.16–7.42 (35H, m). Anal. Calcd for
C62H66O11: C, 75.43; H, 6.74. Found: C, 75.23; H, 6.47.
n-hexane/ether); [a]D29 þ64.68 (c 1.40, CHCl3); H NMR d
0.84–0.93 (3H, m), 1.20–1.37 (10H, m), 1.44–1.62 (2H,
m), 1.72 (1H, ddd, J¼12.8, 11.6, 3.6 Hz), 2.28 (1H, br dd,
J¼12.8, 6.4 Hz), 3.34 (1H, dt, J¼9.6, 6.8 Hz), 3.55–3.82
(5H, m), 4.00 (1H, ddd, J¼11.6, 8.8, 6.4 Hz), 4.43–4.60
(2H, m), 4.63 (1H, d, J¼11.6 Hz), 4.65 (1H, d, J¼12.0 Hz),
4.69 (1H, d, J¼11.6 Hz), 4.89 (1H, d, J¼10.4 Hz), 4.94 (1H,
br d, J¼3.6 Hz), 7.14–7.38 (15H, m). Anal. Calcd for
C35H46O5: C, 76.89; H, 8.48. Found: C, 76.90; H, 8.16.
4.3.18. n-Octyl 3,4,6-tri-O-benzyl-2-deoxy-b-D-arabino-
hexopyranoside (18b). Colorless syrup. Rf 0.47 (5/2 n-
4.3.13. 1,6-Anhydro-2-azido-3-O-benzyl-2-deoxy-4-O-
(2,3,4,6-tetra-O-benzyl-a-D-mannopyranosyl)-b-D-
glucopyranose (16a). Colorless syrup. Rf 0.65 (4/1 toluene/
EtOAc); [a]2D7 þ63.28 (c 0.68, CHCl3); 1H NMR d 3.08 (1H,
br s), 3.41 (1H, dd, J¼1.2, 1.2 Hz), 3.56–3.63 (2H, m),
3.68–4.01 (7H, m), 4.47–4.74 (10H, m), 4.81 (1H, d,
J¼1.6 Hz), 4.87 (1H, d, J¼10.8 Hz), 5.48 (1H, s), 7.23–
1
hexane/ether); [a]D28 216.78 (c 0.98, CHCl3); H NMR d
0.84–0.92 (3H, m), 1.19–1.40 (10H, m), 1.53–1.71 (3H,
m), 2.34 (1H, ddd, J¼12.8, 4.8, 1.6 Hz), 3.36–3.53 (3H, m),
3.61–3.79 (3H, m), 3.89 (1H, dt, J¼9.2, 7.2 Hz), 4.42 (1H,
dd, J¼10.0, 1.6 Hz), 4.53–4.65 (4H, m) 4.68 (1H, d,
J¼11.6 Hz), 4.90 (1H, d, J¼10.0 Hz), 7.16–7.37 (15H, m).

5338
K. Toshima et al. / Tetrahedron 60 (2004) 5331–5339
Anal. Calcd for C35H46O5: C, 76.89; H, 8.48. Found: C,
76.92; H, 8.10.
(1H, dd, J¼9.6, 9.6 Hz), 4.07 (1H, dd, J¼10.8, 2.0 Hz), 4.16
(1H, dd, J¼10.0, 1.6 Hz), 4.49–4.68 (8H, m), 4.77–4.89
(4H, m), 5.00 (1H, d, J¼10.8 Hz), 7.18–7.38 (30H, m).
Anal. Calcd for C55H60O10: C, 74.98; H, 6.86. Found: C,
74.97; H, 6.68.
4.3.19. Isopropyl 3,4,6-tri-O-benzyl-2-deoxy-a-D-
arabino-hexopyranoside (19a). Colorless syrup. Rf 0.38
(30/1 chloroform/EtOAc); [a]2D8 þ76.68 (c 1.88, CHCl3); 1H
NMR d 1.12 (3H, d, J¼6.0 Hz), 1.16 (3H, d, J¼6.0 Hz),
1.74 (1H, ddd, J¼12.8, 11.6, 3.6 Hz), 2.24 (1H, br dd,
J¼12.8, 5.2 Hz), 3.58–3.69 (2H, m), 3.77–3.86 (2H, m),
3.88 (1H, septet, J¼6.0 Hz), 4.01 (1H, ddd, J¼11.6, 8.8,
5.2 Hz), 4.48–4.53 (2H, m), 4.63 (1H, d, J¼11.6 Hz), 4.66
(1H, d, J¼12.4 Hz), 4.68 (1H, d, J¼11.6 Hz), 4.89 (1H, d,
J¼10.8 Hz), 5.08 (1H, br d, J¼3.6 Hz), 7.14–7.38 (15H,
m). Anal. Calcd for C30H36O5: C, 75.60; H, 7.61. Found: C,
75.63; H, 7.41.
4.3.25. 1,6-Anhydro-2-azido-3-O-benzyl-4-O-(3,4,6-tri-
O-benzyl-2-deoxy-a-D-arabino-hexopyranosyl)-2-deoxy-
b-D-glucopyranose (23a). Colorless syrup. Rf 0.43 (2/1
n-hexane/EtOAc); [a]2D7 þ87.18 (c 1.01, CHCl3); 1H NMR d
1.73 (1H, ddd, J¼12.8, 11.6, 4.0 Hz), 2.32 (1H, br dd,
J¼12.8, 4.8 Hz), 3.12 (1H, br s), 3.49–3.64 (4H, m), 3.70
(2H, d, J¼3.6 Hz), 3.94 (1H, ddd, J¼10.0, 4.0, 4.0 Hz),
4.00–4.13 (2H, m), 4.44–4.70 (8H, m), 4.90 (1H, d,
J¼10.8 Hz), 5.00 (1H, d, J¼4.0 Hz), 5.49 (1H, br s), 7.16–
7.40 (20H, m). Anal. Calcd for C40H43N3O8: C, 69.25; H,
6.25; N, 6.06. Found: C, 69.14; H, 5.96; N, 6.10.
4.3.20. Isopropyl 3,4,6-tri-O-benzyl-2-deoxy-b-D-
arabino-hexopyranoside (19b). Colorless syrup. Rf 0.27
(30/1 chloroform/EtOAc); [a]2D9 225.98 (c 1.58, CHCl3); 1H
NMR d 1.15 (3H, d, J¼6.0 Hz), 1.26 (3H, d, J¼6.0 Hz),
1.65 (1H, ddd, J¼12.8, 12.2, 10.0 Hz), 2.30 (1H, ddd,
J¼12.8, 5.6, 1.6 Hz), 3.36–3.51 (2H, m), 3.61–3.71 (3H,
m), 4.01 (1H, septet, J¼6.0 Hz), 4.49–4.65 (5H, m), 4.68
(1H, d, J¼12.0 Hz), 4.89 (1H, d, J¼10.8 Hz), 7.14–7.38
(15H, m). Anal. Calcd for C30H36O5: C, 75.60; H, 7.61.
Found: C, 75.65; H, 7.42.
4.3.26. 1,6-Anhydro-2-azido-3-O-benzyl-4-O-(3,4,6-tri-
O-benzyl-2-deoxy-b-D-arabino-hexopyranosyl)-2-deoxy-
b-D-glucopyranose (23b). Colorless syrup. Rf 0.30 (2/1
n-hexane/EtOAc); [a]2D7 þ9.28 (c 0.85, CHCl3); 1H NMR d
1.75 (1H, ddd, J¼12.0, 12.0, 9.6 Hz), 2.44 (1H, ddd,
J¼12.4, 4.8, 1.6 Hz), 3.18 (1H, br s), 3.39–3.55 (2H, m),
3.62–3.77 (4H, m), 3.85 (1H, br s), 3.92 (1H, dd, J¼1.2,
1.2 Hz), 4.08–4.16 (1H, m), 4.46–4.72 (9H, m), 4.92 (1H,
d, J¼11.2 Hz), 5.48 (1H, br s), 7.19–7.36 (20H, m). Anal.
Calcd for C40H43N3O8: C, 69.25; H, 6.25; N, 6.06. Found:
C, 69.20; H, 5.93; N, 6.01.
4.3.21. Cyclohexyl 3,4,6-tri-O-benzyl-2-deoxy-a-D-
arabino-hexopyranoside (20a). Colorless syrup. Rf 0.46
(30/1 chloroform/EtOAc); [a]2D8 þ80.68 (c 0.82, CHCl3); 1H
NMR d 1.11–1.91 (11H, m), 2.24 (1H, br dd, J¼12.8,
5.2 Hz), 3.49–3.69 (3H, m), 3.72–3.89 (2H, m), 4.02 (1H,
ddd, J¼11.6, 8.8, 5.2 Hz), 4.47–4.54 (2H, m), 4.64 (1H,
d, J¼10.8 Hz), 4.65 (1H, d, J¼12.0 Hz), 4.68 (1H, d,
J¼10.8 Hz), 4.89 (1H, d, J¼10.8 Hz), 5.12 (1H, br d,
J¼4.8 Hz), 7.14–7.39 (15H, m). Anal. Calcd for C33H40O5:
C, 76.71; H, 7.80. Found: C, 76.75; H, 7.49.
Acknowledgements
This research was partially supported by Grant-in-Aid for
the 21st Century COE program ‘KEIO Life Conjugate
Chemistry’ from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan.
4.3.22. Cyclohexyl 3,4,6-tri-O-benzyl-2-deoxy-b-D-
arabino-hexopyranoside (20b). White solid. Rf 0.35
(30/1 chloroform/EtOAc); [a]2D8 226.68 (c 1.00, CHCl3);
References and notes
1
mp 48.0–50.0 8C; H NMR d 1.13–2.05 (11H, m), 2.31
(1H, ddd, J¼12.4, 5.2, 1.6 Hz), 3.47–3.51 (2H, m), 3.61–
3.80 (4H, m), 4.53–4.65 (5H, m), 4.69 (1H, d, J¼12.0 Hz),
4.90 (1H, d, J¼10.8 Hz), 7.19–7.47 (15H, m). Anal. Calcd
for C33H40O5: C, 76.71; H, 7.80. Found: C, 76.74; H, 7.64.
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[a]2D8 þ65.48 (c 0.60, CHCl3); H NMR d 1.69 (1H, ddd,
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