A highly stereoselective construction of β-glycosyl linkages by reductive cleavage of cyclic sugar ortho esters

Article abstract of DOI:10.1021/jo0005870

The preparation of β-glycosides by the reductive cleavage of spiro sugar ortho esters is described in this report. This procedure is based on a concept completely different from those of other methods for glycosylation. Twelve sugar ortho esters that commonly possess perhydrospiro[2H-pyran-2,2'-pyrano[3,2-d][1,3]dioxin] ring systems in their molecules were reduced by LiAlH₄/AlCl₃ or NaCNBH₃/AlCl₃. Among these ortho esters, those (9a-12a) prepared from the D-sugar lactones (1-4) and 2,3-di-O-benzyl-α-D-glucopyranoside (7) or those (19a, 20a) prepared from the L-sugar lactones (5, 6) and 2,3-di-O-benzyl-α-D-galactopyranoside (8) were selectively converted into β-(1 → 4)-glycosides (9b-12b or 19b, 20b) in excellent yields by the treatment of LiAlH₄/AlCl₃. In contrast, the ortho esters (13a-16a or 17a, 18a) that were prepared from combinations of the D-sugar lactones and 8 or those of the L-sugar lactones and 7 were efficiently reduced with NaBH₃CN/AlCl₃ to afford β-(1 → 6)-glycosides (13b-16b or 17b, 18b) selectively. It was remarkable that the resulting disaccharides were obtained with extremely high β-selectivity even in the cases with mannosyl or rhamnosyl glycosides. Moreover, these products would be useful units for the construction of branched saccharides, because the newly formed hydroxy groups could be again glycosylated without further deprotection procedures. The high regio- and stereoselectivity was totally explained by considering the structures and the conformations of these ortho ester molecules and the stereoelectoronic effects of their spiro ring systems. In addition, the preparation of the sugar ortho esters with glucosamine derivatives and the reactivity of these ortho esters are described in this report. N-Phthaloyl glucosamine derivatives (21, 22) were efficiently reacted with the benzyl-protected gluconolactone (1) in the presence of TMSOMe and TMSOTf to afford ortho esters (23a-c). After the conversion of the phthalimido functionality to the dibenzyl amino group, glucosylidene-glucosamine (25) was reduced with LiAlH₄/AlCl₃ to afford β-(1 → 4)-glycoside (26) selectively.

Full text of DOI:10.1021/jo0005870

J . Org. Chem. 2000, 65, 8171-8179
8171
A High ly Ster eoselective Con str u ction of â-Glycosyl Lin k a ges by
Red u ctive Clea va ge of Cyclic Su ga r Or th o Ester s
Hiro Ohtake, Naoto Ichiba, and Shiro Ikegami*
School of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, J apan
shi-ike@pharm.teikyo-u.ac.jp
Received April 17, 2000
The preparation of â-glycosides by the reductive cleavage of spiro sugar ortho esters is described
in this report. This procedure is based on a concept completely different from those of other methods
for glycosylation. Twelve sugar ortho esters that commonly possess perhydrospiro[2H-pyran-2,2′-
pyrano[3,2-d][1,3]dioxin] ring systems in their molecules were reduced by LiAlH4/AlCl3 or NaCNBH3/
AlCl3. Among these ortho esters, those (9a -12a ) prepared from the D-sugar lactones (1-4) and
2,3-di-O-benzyl-R-D-glucopyranoside (7) or those (19a , 20a ) prepared from the L-sugar lactones (5,
6) and 2,3-di-O-benzyl-R-D-galactopyranoside (8) were selectively converted into â-(1 f 4)-glycosides
(9b-12b or 19b, 20b) in excellent yields by the treatment of LiAlH4/AlCl3. In contrast, the ortho
esters (13a -16a or 17a , 18a ) that were prepared from combinations of the D-sugar lactones and 8
or those of the L-sugar lactones and 7 were efficiently reduced with NaBH3CN/AlCl3 to afford â-(1
f 6)-glycosides (13b-16b or 17b, 18b) selectively. It was remarkable that the resulting
disaccharides were obtained with extremely high â-selectivity even in the cases with mannosyl or
rhamnosyl glycosides. Moreover, these products would be useful units for the construction of
branched saccharides, because the newly formed hydroxy groups could be again glycosylated without
further deprotection procedures. The high regio- and stereoselectivity was totally explained by
considering the structures and the conformations of these ortho ester molecules and the
stereoelectoronic effects of their spiro ring systems. In addition, the preparation of the sugar ortho
esters with glucosamine derivatives and the reactivity of these ortho esters are described in this
report. N-Phthaloyl glucosamine derivatives (21, 22) were efficiently reacted with the benzyl-
protected gluconolactone (1) in the presence of TMSOMe and TMSOTf to afford ortho esters (23a -
c). After the conversion of the phthalimido functionality to the dibenzyl amino group, glucosylidene-
glucosamine (25) was reduced with LiAlH4/AlCl3 to afford â-(1 f 4)-glycoside (26) selectively.
In tr od u ction
investigated for the provision of flexible strategy in
oligosaccharide synthesis.
As the biological significance of oligosaccharides and
glyco-conjugates is being revealed, the development of
methods for the chemical construction of glycosides is
increasingly necessitated.1 The most important process
in saccharide synthesis is the glycosidic bond formation,
and various useful methods for glycosylation have been
developed in recent years.2 The known glycosylations are
generally based on the activation of glycosyl donors with
leaving groups such as fluoride and trichloroacetimidate
and phosphorus-centered leaving groups3 by appropriate
promoters. However, we think that other approaches to
the construction of glycosyl linkages should also be
We previously reported a new two-step glycosylation
procedure, which was a type of method completely
different from other ones.4 As shown in Scheme 1, the
first step in our procedure is the formation of ortho esters
from two sugar moieties, and the second is the reductive
cleavage of a C-O ortho ester bond. With this method,
three glycosyl-(1 f 4)-glucosides (9b, 10b, 11b) were
efficiently prepared from the sugar lactones (1-3) and
the 2,3-di-O-protected glucopyranoside (7) via the ortho
esters (9a , 10a , 11a ).4a,b It was remarkable that the
complete â-selectivity was observed at the anomeric
centers of the resulting disaccharides. Moreover, these
disaccharides was expected to be useful units for the
construction of branched saccharides, because the newly
formed alcohol functionality could be again glycosylated.
In this paper, we report the details of the preparation
of the glycosides from various combinations of sugar
lactones and â-diol type sugars, including the above three
cases. All of the glycosides reported here were commonly
prepared via 4-O,6-O-glycosylideneglycosides. We re-
vealed that the regio- and stereoselectivity in the reduc-
tion of this type of the sugar ortho esters was explained
* Tel: (+81) 426-85-3728. Fax: (+81) 426-85-1870.
(1) Recent review: Boons, G.-J . Tetrahedron 1996, 52, 1095.
(2) Recent review: (a) Paulsen, H. Angew. Chem., Int. Ed. Engl.
1990, 29, 823. (b) Banoub, J .; Boullanger, P.; Lafont, D. Chem. Rev.
1992, 92, 1167. (c) Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503.
(d) Danishefsky, S. J .; Bilodeau, M. T. Angew. Chem., Int. Ed. Engl.
1996, 35, 1380.
(3) (a) Hashimoto, S.; Honda, T.; Ikegami, S. J . Chem. Soc., Chem.
Commun. 1989, 685. (b) Hashimoto, S.; Honda, T.; Ikegami, S.
Heterocycles 1990, 30, 775. (c) Hashimoto, S.; Honda, T.; Ikegami, S.
Tetrahedron Lett. 1990, 31, 4769. (d) Hashimoto, S.; Honda, T.;
Ikegami, S. Chem. Pharm. Bull. 1990, 38, 2323. (e) Hashimoto, S.;
Yanagiya, Y.; Honda, T.; Harada, H.; Ikegami, S. Tetrahedron Lett.
1992, 33, 3523. (f) Hashimoto, S.; Umeo, K.; Sano, A.; Watanabe, N.;
Nakajima, M.; Ikegami, S. Tetrahedron Lett. 1995, 36, 2251. (g)
Hashimoto, S.; Honda, T.; Yanagiya, Y.; Nakajima, M.; Ikegami, S. J .
Synth. Org. Chem. J pn. 1995, 53, 620.
(4) (a) Ohtake, H.; Iimori, T.; Ikegami, S. Tetrahedron Lett. 1997,
38, 3413. (b) Iimori, T.; Ohtake, H.; Ikegami, S. Tetrahedron Lett. 1997,
38, 3415. (c) Ohtake, H.; Iimori, T.; Shiro, M.; Ikegami, S. Heterocycles
1998, 47, 685. (d) Ohtake, H.; Iimori, T.; Ikegami, S. Synlett 1998, 1420.
10.1021/jo0005870 CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/31/2000

8172 J . Org. Chem., Vol. 65, No. 24, 2000
Ohtake et al.
Sch em e 1
Sch em e 2
Sch em e 3
by considering the stereoelectronic effects of the spiro ring
systems in ortho ester molecules, which is also reported
here in detail. Further, we describe the preparation of
the sugar ortho esters with an amino functionality and
the reduction of these compounds together in this report.
P r ep a r a tion of th e Su ga r Or th o Ester s. The first
step in our reductive glycosylation method is the forma-
tion of the sugar ortho esters. We improved the method
for the formation of ortho esters and prepared the 12
sugar ortho esters (9a -20a ) in 80-92% yields. We used
the six sugar lactones 2,3,4,6-tetra-O-benzyl-D-glucono-
lactone (1),5 2,3,4,6-tetra-O-benzyl-D-galactonolactone (2),6
2,3,4,6-tetra-O-benzyl-D-mannonolactone (3),6 2,3,4-tri-
O-benzyl-D-fuconolactone (4),9 2,3,4-tri-O-benzyl-L-fu-
conolactone (5),7 and 2,3,4-tri-O-benzyl-L-rhamnonolac-
tone (6)9 in this preparation (Scheme 2). The ortho esters
9a -14a were prepared from these sugar lactones and
2,3-di-O-benzyl-R-D-glucopyranoside (7), and the ortho
esters 15a -20a were the products of the reaction of these
lactones with 2,3-di-O-benzyl-R-D-galactopyranoside (8).8
All of these ortho esters possess perhydrospiro[2H-pyran-
2,2′-pyrano[3,2-d][1,3]dioxin] ring systems commonly in
their molecules and were remarkably afforded as single
isomers despite the fact that two stereoisomers were
possible around the spiro centers. The absolute configu-
rations of the anomeric centers are indicated in Tables 1
and 2. The details of the preparation and the structure
determination of these ortho esters have been reported
in the preceding paper.9
Sch em e 4
10
and revealed that the combination of LiAlH4 and AlCl3
was an effective reagent for this purpose (Scheme 4).
Table 1 summarizes the results of the reduction of the
six sugar ortho esters (9a -12a or 19a , 20a ) with LiAlH4/
AlCl3, which were prepared from the combinations of
D-sugar lactones (1-4) and 7 or from those of the L-sugar
lactones (5, 6) and 8. As shown in entry 1, the reduction
of 9a smoothly proceeded with 2 equiv of reagents in 2 h
at room temperature to afford glucosyl-â-(1 f 4)-gluco-
side 9b in 92% yield, and other possible isomers, 9c, 9d
and 9e, were not detected. Also in the cases with the
ortho esters 10a -12a (entry 2-4), glycosyl-â-(1 f 4)-
glucosides 10b, 11b,11 12b were obtained in excellent
yields (92-98%) with complete regio- and stereoselectiv-
ity. The reduction of the two ortho esters (19a , 20a )
containing L-sugar moieties proceeded efficiently under
the same reaction conditions, and glycosyl-â-(1 f 4)-
galactosides were produced selectively again with excel-
lent yields (96-99%; entries 5 and 6). The stereochem-
istry of the anomeric centers of the resulting disaccharides
were determined to be â by considering the coupling
constant of the signals of the anomeric protons in 1H
NMR or by comparing the spectral data of the products
with authentic samples prepared by usual glycosylation
methods.
Red u ction of th e Su ga r Or th o Ester s w ith LiAlH4/
AlCl3. In the reduction of these sugar ortho esters, there
are four possible glycoside products for each ortho ester.
For example, the possible products of the glucosylidene-
glucoside 9a are glucosyl-R- or â-(1 f 4)-glucoside (9c or
9b) and glucosyl-R- or â-(1 f 6)-glucoside (9e or 9d )
(Scheme 3). As reported in a previous paper,4b we
surveyed the reductants to find the efficient conditions
for the selective cleavage of the spiro sugar ortho esters
The results in Table 1 were noteworthy first from the
point that the sterically congested 4-O positions of sugar
compounds were efficiently glycosylated by this method.
More noticeable was that the resulting disaccharides
were afforded with complete â-selectivity even in the
cases with mannosyl and rhamnosyl donors. While ste-
reoselective â-mannosylations or â-rhamnosylations based
on several new concepts have been reported recently,12
our procedure is superior in terms of efficiency and
selectivity.
(5) (a) Kuzuhara, H.; Fletcher, H. G., J r. J . Org. Chem. 1967, 32,
2531. (b) Hanessian, S.; Ugolini, A. Carbohydr. Res. 1984, 130, 261.
(6) Lewis, M. D.; Cha, J . K.; Kishi, Y. J . Am. Chem. Soc. 1982, 104,
4976.
(7) Cai, S.; Stroud, M. R.; Hakomori, S.; Toyokuni, T. J . Org. Chem.
1992, 57, 6693.
(10) (a) Bhattacharjee, S. S.; Gorin, P. A. J . Can. J . Chem. 1969,
47, 1195. (b) Lipta´k, A.; J oda´l, I.; Na´na´si, P. Carbohydr. Res. 1975,
44, 1.
(8) Kiss, J . v.; Burkhardt, F. Helv. Chim. Acta 1970, 53, 1000.
(9) Ohtake, H.; Ichiba, N.; Shiro, M.; Ikegami, S. J . Org. Chem. 2000,
65, 8164.
(11) Compound 10b was hydrogenated to be converted into the
corresponding debenzylated compound as reported previously: Barresi,
F.; Hindsgaul, O. J . Am. Chem. Soc. 1991, 113, 9376.

Highly Stereoselective Construction of â-Glycosyl Linkages
J . Org. Chem., Vol. 65, No. 24, 2000 8173
Ta ble 1. Red u ction of Su ga r Or th o Ester s w ith LiAlH4/AlCl3
a
These reactions were carried out for 1 h at rt under Ar in Et2O/CH2Cl2 ([ortho ester] ) 50 mM, 2 equiv LiAlH4, 2 equiv AlCl3). Yields
are isolated yields.
We also attempted the reduction by LiAlH4/AlCl3 of the
sugar ortho esters prepared from the combinations of the
D-sugar lactones and 8 (15a -18a ) and from those of the
L-sugar lactones and 7 (13a , 14a ). However, these ortho
esters were not efficiently reduced or were converted into
multiple products by treating with an excess amount of
reagents.
reagent for this purpose. Although the reactivity of
DIBAL was similar to that of LiAlH4/AlCl3, it was
revealed that the reduction of these ortho esters with
NaBH3CN proceeded efficiently in the presence of AlCl3.
In Table 2, the results of the reduction of six sugar
ortho esters 13a -18a with NaBH3CN/AlCl3 are sum-
marized. As shown in entries 1, 2 and 4, the gluco-
sylidene- (15a), galactosylidene- (16a) and D-fucosylidene-
galactosides (18a ) were efficiently reduced with these
reagents in 1.5-2 h at room temperature using toluene/
CH3CN as solvents to afford glycosyl-â-(1 f 6)-galacto-
sides 15b, 16b, and 18b selectively with 88-97% yields
(Scheme 5). Although the reaction did not proceed
completely in the case of the mannosylidene ortho ester
17a (entry 3), mannosyl-â-(1 f 6)-galactoside 17b was
Red u ction of th e Su ga r Or th o Ester s w ith Na BH3-
CN/AlCl3. To find efficient reagents for the reduction of
remainine six sugar ortho esters 13a -18a , we again
investigated the reactivity of several reductants.13-17 As
described in the previous paper,4b DIBAL13 and NaBH3-
CN/acid14 also had potential as the reagents for the
conversion of the sugar ortho esters to glycosides, while
BH3 or Et3SiH/acid16 or Al(i-Bu)3 was not an effective
15

8174 J . Org. Chem., Vol. 65, No. 24, 2000
Ta ble 2. Red u ction of Su ga r Or th o Ester s w ith Na BH3CN/AlCl3
Ohtake et al.
a
These reactions were carried out at rt under Ar in toluene/CH3CN ([ortho ester] ) 50 mM, 7 equiv NaBH3CN, 5 equiv AlCl3, 100 mg
MS3A/2 mL solvents). Yields are isolated yields. Yield 91% based on conversion. c R-(1 f 6)-Isomer was detected (6%).
b
Sch em e 5
was also effective for the preparation of several glycosyl-
â-(1 f 6)-glycosides. Unfortunately, the reaction with
mannosylidene (17a ) or rhamnosylidene ortho ester (14a )
did not proceed efficiently enough; however, the â-selec-
tivities obtained here, especially in the case with the
ortho ester 17a , were excellent. As shown in entries 4
and 5, the yields of the products in the reduction of
fucosylidene ortho esters (13a , 18a ) were relatively low
compared to that of galactosylidene ortho ester (16a ),
which may be caused by the instability of fucosylidene
moieties under the reduction conditions.
also afforded as the only resulting glycoside product (91%
based on conversion). L-Fucosylideneglucoside 13a was
reduced smoothly to afford L-fucosyl-â-(1 f 6)-glucosides
(13b) selectively (entry 5). However, the reduction of
L-rhamnosylideneglucoside 14a proceeded slowly, and
â-(1 f 6)-isomer 14b was obtained in a relatively lower
yield accompanied by the production of a small amount
of the R-1,6-isomer 14c (R:â ) 7:93; entry 6). These
results revealed that the reductive glycosylation method
We first used the ethereal solution of HCl instead of
AlCl3 dissolved in CH3CN because HCl solution was most
frequently used for the acceleration of the reactivity of

Highly Stereoselective Construction of â-Glycosyl Linkages
J . Org. Chem., Vol. 65, No. 24, 2000 8175
F igu r e 1. Typical four conformations of sugar ortho ester molecules calculated by LOMD18 using MacroModel ver 6.019. All of
the benzyl groups and the hydrogen atoms on the molecules were omitted.
NaBH3CN. However, the sugar ortho esters decomposed
to the corresponding lactones and diols by the treatment
of etheral HCl. Although it was not clear why these ortho
esters were quite stable in ethereal or CH3CN solution
of AlCl3, it would be a plausible explanation that AlCl3
strongly trapped the contaminated anion, such as OH-,
which were necessary for the decomposition of these ortho
esters.
The six sugar ortho esters for which LiAlH4/AlCl3 were
effective reagents were tried to be reduced with NaBH3-
CN/AlCl3. However, the mismatching between the re-
agents and ortho esters again occurred. The reactions of
these ortho esters did not proceed so efficiently or
selectively as those of the ortho esters listed in Table 2.
Con sid er a tion of th e High Regio- a n d Ster eose-
lectivity in th e Red u ction of th e Su ga r Or th o
Ester s on th e Ba sis of Th eir Str u ctu r es. Above
results revealed that the prepared 12 sugar ortho esters
were separated into two groups from the point of the
reactivity of the reductants and of the regioselectivity in
their reductions. According to the X-ray crystallographic
analysis and the molecular modeling studies18,19 reported
in the preceding paper,9 these ortho esters were classified
into four groups from the points of the structures of their
ring systems. Remarkably, it was revealed that these two
classifications were closely related and that the difference
or similarity among the reactivity of ortho esters was well
explained by considering the structures of the ring
systems in their molecules.
As reported in the preceding paper,9 the structures and
conformations of the spiro ring systems of the formed
ortho esters depended on whether D- or L-sugar lactones
were used as glycosylidene parts and on whether 7 or 8
was used as the diol part. For example, the ring systems
of the sugar ortho esters 9a -12a prepared from the
D-sugar lactones 1-4 and 7 had the same structure. In
Figure 1, the typical four structures of the spiro ring
systems of ortho esters are shown. The structures A-D
in Figure 1 are illustrated on the basis of the calculated
conformations20 of the ortho esters 11a , 14a , 17a and
20a , respectively. The 5′-oxygen atoms of these ortho
esters are commonly in the axial positions of the dioxane
rings, which are located at the centers of these molecules
(see upper four structures in Figure 1). It is reasonable
to think that the stability of these conformations is
caused by the anomeric effects derived from the oxygen
atoms of dioxane rings.21 These effects were so significant
(12) (a) Gorin, P. A. J .; Perlin, A. S. Can. J . Chem. 1961, 39, 2474.
(b) Betaneli, V. I.; Ovchinnikov, M. V.; Backinowsky, L. V.; Kochetkov,
N. K. Carbohydr. Res. 1980, 84, 211. (c) Paulsen, H.; Lockhoff, O. Chem.
Ber. 1981, 114, 3102. (d) Srivastava, V. K.; Schuerch, C. J . Org. Chem.
1981, 46, 1121. (e) Garegg, P. J .; Ossowski, P. Acta Chem. Scand. 1983,
B37, 249. (f) Rathore, H.; From, A. H. L.; Ahmed, K.; Fullerton. D. S.
J . Med. Chem. 1986, 29, 1945. (g) Crich, D.; Sun, S. J . Org. Chem.
1997, 62, 1198. â-Mannoside formation via an inversion of configura-
tion at C-2 by a nucleophilic substitution: (h) Kunz, H.; Gu¨nther, W.
Angew. Chem., Int. Ed. Engl. 1988, 27, 1086. â-Mannoside formation
by radical inversions at anomeric center: (i) Brunckova, J .; Crich, D.;
Yao, Q. Tetrahedron Lett. 1994, 35, 6619. (j) Yamazaki, N.; Eichen-
berger, E.; Curran, D. P. Tetrahedron Lett. 1994, 35, 6623. â-Mannoside
formation by stereoselective reductions of 2-keto-â-glucoside: (k) Liu,
K. K.-C.; Danishefsky, S. J . J . Org. Chem. 1994, 59, 1892. (l)
Lichtenthaler, F. W.; Schneider-Adams, T.; Immel, S. J . Org. Chem.
1994, 59, 6735. â-Mannoside formation using 1, 2-O-cis-stannylene
acetals: (m) Hodosi, G.; Kova´c, P. J . Am. Chem. Soc. 1997, 119, 2335.
â-Mannoside formation by aglycon delivery concept: (n) Barresi, F.;
Hindsgaul, O. Can. J . Chem. 1994, 72, 1447. (o) Dan, A.; Ito, Y.; Ogawa,
T. Tetrahedron Lett. 1995, 36, 7487. (p) Dan, A.; Ito, Y.; Ogawa, T. J .
Org. Chem. 1995, 60, 4680. (q) Stork, G.; La Clair, J . J . J . Am. Chem.
Soc. 1996, 118, 247. â-Mannoside formation via intramolecular nu-
cleophilic substitution: (r) Ivanova, I. A.; Nikolaev, A. V. J . Chem. Soc.,
Perkin Trans. 1 1998, 3093.
(13) (a) Takasu, M.; Naruse, Y.; Yamamoto, H. Tetrahedron Lett.
1988, 29, 1947. (b) Mikami, T.; Asano, H.; Mitsunobu, O. Chem. Lett.
1987, 2033.
(14) (a) Garegg, P. J .; Hultberg, H.; Wallin, S. Carbohydr. Res. 1982,
108, 97. (b) J ohansson, R.; Samuelsson, B. J . Chem. Soc., Perkin Trans.
1 1984, 2371.
(15) Stork, G.; Rychnovsky, S. D. J . Am. Chem. Soc. 1987, 109, 1565.
(16) (a) Tsunoda, T.; Suzuki, M., Noyori, R.; Tetrahedron Lett. 1979,
4679. (b) Mori, A.; Ishihara, K.; Yamamoto, H. Tetrahedron Lett. 1986,
27, 987. (c) DeNinno, M. P.; Etienne, J . B.; Duplantier, K. C.
Tetrahedron Lett. 1995, 36, 669.
(17) Several recent reports for the preparation of partially protected
sugar derivatives by reductive methods besides those referred to
above: (a) Arasappan, A.; Fuchs, P. L. J . Am. Chem. Soc. 1995, 117,
177. (b) Okawa, M.; Liu, W. C.; Nakai, Y.; Koshida, S.; Fukase, K.;
Kusumoto, S. Synlett. 1996, 1179. (c) J iang, L.; Chan, T.-H. Tetrahe-
dron Lett. 1998, 39, 355.
(18) (a) Kolossva´ry, I.; Guida, W. C. J . Am. Chem. Soc. 1996, 118,
5011. (b) Cheng, G.; Guida, W. C.; Still, W. C. J . Am. Chem. Soc. 1989,
111, 4379.
(19) Mohamadi, F.; Richards, N. G. J .; Guida, W. C.; Liskamp, R.;
Lipton, M.; Caufield, C.; Chang, G.; Hendricson, T.; Still, W. C. J .
Comput. Chem. 1990, 11, 440.
(20) LOMD for ortho ester molecules was continued until around
3000 conformers for each molecule were generated. Even if the steps
in LOMD were not enough for the determination of the conformations
of the whole molecules including benzyl or phthaloyl protective groups,
the conformations of the ring systems in the lower energy conformers
were the same in each case.
(21) (a) Lemieux, R. U. In Molecular Rearrangements; De Mayo, P.,
Ed.; Interscience: New York, 1964. (b) Kirby, A. J . The Anomeric Effect
and Related Stereoelectronic Effects at Oxygen; Springer-Verlag: Ber-
lin, 1983.

8176 J . Org. Chem., Vol. 65, No. 24, 2000
Ohtake et al.
Sch em e 6
Sch em e 7
reduction with these reagents have not been clarified
even in the cases with simple substrates such as 27a , 4-
and 6-benzyl glycosides (27b and 27c) were afforded
selectively from 27a with LiAlH4/AlCl3 and NaBH3CN/
HCl, respectively.
Finally, the mechanism that accounts for the extremely
high â-selectivity should be mentioned. This stereoselec-
tivity would be explained by considering the electronic
advantage of the axial anion attack.23 Moreover, it
seemed reasonable to think that a hydride anion on the
reducing reagents attacked to the intermediates im-
mediately after the dioxane ring opening or that the
reactions shown in Scheme 6 proceeded concertedly.
Thus, the attack from an axial direction from which the
eliminated oxygen atoms had been bound would be
advantageous. As proton atoms attached to the anomeric
carbons from the axial direction, â-glycosides were af-
forded as the resulting products. The high â-selectivity
might be the most interesting and important feature of
this reductive glycosylation procedure. This superior
selectivity was realized by developing a glycosylation
method based on the completely different concept.
P r ep a r a tion a n d Red u ction of th e Su ga r Or th o
Ester s Con ta in in g Glu cosa m in e Der iva tives. The
preparation of sugar ortho esters with glucosamine
derivatives and the reactivities of these ortho esters were
next investigated. We first tried to use N-acetylglu-
cosamine derivatives as diol type sugar substrates for the
preparation of ortho esters; however, these reactions did
not proceed efficiently. As the addition of amide com-
pounds such as DMF inhibited the preparations of the
ortho esters from sugar lactones and 7, the amide part
of the substrates might disturb the reactions by a simple
interaction with Lewis acid catalyst. Fortunately, it was
revealed that the reactions with phthalimide derivatives,
which were easily prepared by the established method,
proceeded smoothly under the conditions described in the
preceding paper.9 As shown in Scheme 8, N-phthaloyl
glucosamine 2124 was reacted with 1 in the presence of
TMSOMe and TMSOTf to afford 23a in 86% yield. The
resulting ortho ester product was afforded as a single
isomer, despite the fact that two stereoisomers were
possible around the spiro center. It was estimated by
molecular modeling studies18-20,25 that the configuration
of the anomeric center of 23a was R and that the
conformation of the ring systems of 23a was shape type
A in Figure 1 as in the case of the related ortho ester 9a .
that all of the ortho esters were afforded as single isomers
in the preparation. Considering the structures of the ring
systems of the prepared sugar ortho esters, reduction
results indicated that the ortho esters (9a -12a , or 19a ,
20a ) with the A or D type ring system were reduced by
LiAlH4/AlCl3 to afford the corresponding glycosyl-â-(1 f
4)-glycosides in excellent yields but that the reduction
with these reagents did not proceed efficiently in the case
of the ortho esters (13a , 14a , or 15a -18a ) with the B or
C type ring system. Further, it was revealed that the
ortho esters with the B or C type ring system were
efficiently converted into glycosyl-â-(1 f 6)-glycosides by
the reduction with NaBH3CN/AlCl3 but that this combi-
nation of the reagents was not effective for the efficient
and selective reduction of the other two types (A or D) of
ortho esters.
To find the reasons for these features of the reduction
results, we tried to reveal the difference or similarity
among four structures of the spiro ring systems in Figure
1 and paid attention to the positions of two oxygen atoms
of the dioxane ring in each structure with respect to the
pyrane ring of glycosylidene moiety. The lower four
structures in Figure 1 show the shapes of the spiro ring
systems viewed from the axial directions of dioxane rings.
It should be noted that the 6-position oxygen atoms were
located in the axial positions of pyrane rings in the cases
of structures A and D but that 4-position oxygen atoms
were in the axial positions in the cases of structure B
and C. These considerations revealed the common feature
of the above reduction results, that all of the products in
Tables 1 and 2 resulted from the selective ring opening
at the bonds between the anomeric carbons and the axial
oxygen atoms. In the cases of the present reductions, it
was appropriate to think that the initial step was the
elimination of one of the oxygen atoms in the dioxane
ring of each sugar ortho ester and that the second step
was the attack of a hydride anion to a resulting oxonium
cation (Scheme 6). The higher reactivity of the substit-
uents at the axial positions of the pyran rings in elimina-
tion reactions compared to those at the equatorial
positions can be rationally explained by the stereoelec-
tronic effects.22
It was interesting that only two ortho ester products,
23b and 23c, were afforded selectively as the products
of the reaction of the triol sugar 2224 with 1 (Scheme 8).
Both of these ortho esters were 4-O,6-O-glucosylidene-
glucosamine, and the configurations of the spiro centers
of these ortho esters were the same. 3-Trimethylsilyloxy
The matching or mismatching between the reductants
and the substrates in the present reductions was compat-
ible to the well-known selectivity in the reduction of
4-O,6-O-benzylideneglycosides shown in Scheme 7.10,14
Although the reasons for the high regioselectivity in the
(23) Eliel, E. L.; Nader, F. W. J . Am. Chem. Soc. 1970, 92, 584.
(24) Ogawa, T.; Nakabayashi, S. Carbohydr. Res. 1981, 97, 81.
(25) LOMD for two possible isomers of ortho ester 23a were
performed, and ∆E values of the most stable comformers of these
isomers were compared.9
(22) Deslongchamps, P.; Che´nevert, R.; Taillefer, R. J .; Moreau, C.;
Saunders J . K. Can. J . Chem. 1975, 53, 1601.

Highly Stereoselective Construction of â-Glycosyl Linkages
Sch em e 8
J . Org. Chem., Vol. 65, No. 24, 2000 8177
Sch em e 9
product 23c was easily converted into 3-hydroxy product
23b by the treatment of methanolic solution of K2CO3
formations of these molecules are restricted by their
unique ortho ester linkages.
26
in 96% yield. Namely, it was possible to prepare a single
ortho ester product from trihydroxy sugar 22 and 1
selectively without further protection. The configuration
of these ortho esters estimated also to be R, because 23a
was obtained from 23b by benzylation with NaH and
benzyl bromide.
Con clu sion
Twelve sugar ortho esters (9a -20a ) that possess
perhydrospiro[2H-pyran-2,2′-pyrano[3,2-d][1,3]dioxin] ring
systems commonly in their molecules were reduced with
LiAlH4/AlCl3 or NaBH3CN/AlCl3. The ortho esters (9a -
12a ) prepared from the D-sugar lactones (1-4) and 7 or
those (19a , 20a ) prepared from the L-sugar lactones (5,
6) and 8 were selectively converted into â-(1 f 4)-
glycosides in excellent yields by the treatment of LiAlH4/
AlCl3. In contrast, the other six ortho esters (15a -18a ,
or 13a , 14a ) that were prepared from the combination
of the D-sugar lactones and 8 or those of the L-sugar
lactones and 7 were efficiently reduced with NaBH3CN/
AlCl3 to afford â-(1 f 6)-glycosides. It was remarkable
that extremely high â-selectivity was observed at the
anomeric centers of the resulting disaccharides even in
the cases with mannosyl or rhamnosyl glycosides. This
superior selectivity was realized by developing a glyco-
sylation method based on a completely different concept.
Considering the structures of these sugar ortho esters,
all of the products were afforded as the result of the
cleavage of dioxane rings at the bonds between the
anomeric carbons and the oxygen atoms located in the
axial positions of pyrane rings of glycosylidene moieties.
The higher reactivity at the axial position was rationally
explained by considering anomeric effects. It was also
revealed that LiAlH4/AlCl3 and NaBH3CN/AlCl3 were the
appropriate reagents for the reduction at 6-O and at 4-O,
respectively. It should be noted that the resulting disac-
charides would be useful units for the synthesis of
branched saccharides because they could be used as
glycosyl acceptors without further deprotection proce-
As it was estimated that the conformation of the ring
systems of 23a was the A-type shape, this ortho ester
was expected to be reduced efficiently by LiAlH4/AlCl3.
However, the N-phthalimide functionality was not stable
under the reduction conditions with this reagent combi-
nation. Thus, 23a was treated with an excess amount of
ethylenediamine in ethanol under reflux conditions ac-
cording to the reported method for the dephthalation of
usual amino sugar glycosides27 and was converted into
24 quantitatively (Scheme 9). The dibenzylamino com-
pound 25 was also prepared from 24 using NaH and
benzyl bromide in 94% yield (Scheme 9). Although 24
resisted the treatment of LiAlH4/AlCl3, 25 was efficiently
reduced with 2 equiv of these reagents to afford â-(1 f
4)-glycoside 26 selectively (Scheme 9), which supported
the above estimation for the conformation of the ortho
ester ring system.
The present results with glucosamine derivatives may
not be so interesting from the point of developing a
method for glycosylation; however, they would provide
useful information on amino sugar ortho esters. These
ortho esters raise interest from the point of designing
amino pseudo-saccharide compounds, because the con-
(26) Hurst, D. T.; McInnes, A. G. Can. J . Chem. 1965, 43, 2004.
(27) Kanie, O.; Crawley S. C.; Palcic, M. M.; Hindsgaul, O. Carbo-
hydr. Res. 1993, 243, 139.

8178 J . Org. Chem., Vol. 65, No. 24, 2000
Ohtake et al.
722 (M - Bn + Na)+; HRMS(FAB) calcd for C48H54O10Na
813.3615, found 813.3615.
dures. In addition, the method for the preparation of the
amino sugar ortho esters was developed, and the features
of these ortho esters were revealed. These results would
provide useful information for the designing of pseudo-
saccharide compounds containing an amino functionality.
Meth yl 2,3-d i-O-ben zyl-4-O-(2,3,4-tr i-O-ben zyl-â-L-fu -
cop yr a n osyl)-r-D-ga la ctop yr a n osid e (19b): colorless syrup;
[R]22 +31.2° (c 1.0, CHCl3); IR (neat, cm-1) 3380, 2926, 1460,
D
1377; MS(FAB) m/z 829 (M + K)+, 813 (M + Na)+, 722 (M -
Bn + Na)+; HRMS(FAB) calcd for C48H54O10Na 813.3615, found
813.3616.
Exp er im en ta l Section
Meth yl 2,3-di-O-ben zyl-4-O-(2,3,4-tr i-O-ben zyl-â-L-r h am -
Gen er a l. Melting points are uncorrected. 1H and 13C NMR
spectra were recorded with a 400 MHz (1H NMR) pulse Fourier
transform NMR spectrometer in CDCl3 solution with tetram-
ethylsilane as an internal standard. Thin-layer chromatogra-
phy (TLC) was performed on precoated plates (Merck TLC
aluminum sheets silica 60 F254) with detection by UV light or
with phosphomolybdic acid in ethanol/H2O followed by heating.
Column chromatography was performed using SiO2 (Wakogel
C-200, Wako).
Ma ter ia ls. Solvents were freshly distilled prior to use.
Reagents for the reduction of sugar ortho esters and the
preparation of glucosamine ortho esters were commercial
products and were used as received or were purified according
to the typical procedures, if necessary. The preparation of the
sugar ortho esters except glucosamine derivatives was reported
in the preceding paper. Benzyl 3-O-benzyl-2-deoxy-2-phthal-
imido-â-D-glucopyranoside (21)24 and benzyl 2-deoxy-2-phthal-
imido-â-D-glucopyranoside (22)24 were prepared according to
the established methods.
n opyr an osyl)-r-D-galactopyr an oside (20b): colorless needle;
mp 78.5-79.5 °C; [R]26 +64.6° (c 0.4, CHCl3); IR (KBr, cm-1
)
D
3348, 2926, 2855, 1462, 1377; MS(FAB) m/z 829 (M + K)+,
813 (M + Na)+, 722 (M - Bn + Na)+; HRMS(FAB) calcd for
C
C
48H54O10Na 813.3615, found 813.3600, Anal. Calcd for
48H54O10‚1/2H2O: C, 72.07; H, 6.93. Found: C, 72.05; H, 7.01.
Red u ction of th e Su ga r Or th o Ester s w ith Na BH3CN/
AlCl3. To a solution of ortho ester 15a (90 mg, 0.1 mmol) in
toluene (1.0 mL) was added NaBH3CN (42 mg, 0.67 mmol) and
molecular sieves 3Å (powder, 100 mg). The resulting suspen-
sion was stirred at room temperature under Ar, and a solution
of AlCl3 (67 mg, 0.5 mmol) in CH3CN (1.0 mL) was added
slowly. After 2 h of stirring, the mixture was diluted with
EtOAc (10 mL), and a saturated potassium sodium tartrate
solution (5 mL) was added cautiously. The mixture was stirred
vigorously for 1 h, and then the organic layer was separated.
The aqueous layer was extracted again with EtOAc, and the
combined extract was washed with brine, dried over Na2SO4,
filtered, and evaporated to dryness. The product was purified
by silica gel column chromatography (Et2O/hexane 1:1, then
2:1) to afford 15b as a colorless syrup (84 mg, 93%). Two of
the following glycosides, 16b and 18b, were crystalline com-
pounds, and the needles of them were obtained by recrystal-
lization from Et2O/hexane.
Ca lcu la tion s. Low-mode search (LOMD)18 for ortho ester
23a was performed using MacroModel ver. 6.019 with the
MM2* derivative of the MM2 force field on a Silicon Graphics
IRIS-Indigo workstation until more than 3000 conformers were
generated.
Meth yl 2,3-d i-O-ben zyl-6-O-(2,3,4,6-tetr a -O-ben zyl-â-D-
glu co-p yr a n osyl)-r-D-ga la ct op yr a n osid e (15b ): colorless
syrup; [R]25D +21.0° (c 0.8, CHCl3); IR (neat, cm-1) 3350, 2924,
1462, 1377; MS(FAB) m/z 935 (M + K)+, 919 (M + Na)+, 828
(M - Bn + Na)+; HRMS(FAB) calcd for C55H58O11Na 919.4034,
found 919.4022.
Red u ction of th e Su ga r Or th o Ester s w ith LiAlH4/
AlCl3. To a solution of ortho ester 9a (45 mg, 0.05 mmol) in
1:1 Et2O/CH2Cl2 (0.5 mL) was added LiAlH4 (4 mg, 0.1 mmol).
The resulting suspension was stirred at room temperature
under Ar, and an ethereal solution (0.5 mL) of AlCl3 (13 mg,
0.1 mmol) was slowly added. After 1 h of stirring, the mixture
was diluted with Et2O (4 mL), and a saturated potassium
sodium tartrate solution (5 mL) was added cautiously. The
mixture was stirred vigorously for 30 min, and then the ether
layer was separated. The aqueous layer was extracted twice
with Et2O and then with CH2Cl2. The combined extract was
washed with brine, dried over Na2SO4, filtered, and evaporated
to dryness. The product was purified by silica gel column
chromatography (Et2O/hexane 2:1, then Et2O) to afford 9b as
white solid (42 mg, 92%). The needles of this compound and
the glycosides 10b, 20b were obtained by recrystallization from
Et2O/hexane.
Meth yl 2,3-d i-O-ben zyl-6-O-(2,3,4,6-tetr a -O-ben zyl-â-D-
ga la cto-p yr a n osyl)-r-D-ga la ctop yr a n osid e (16b): colorless
needle; mp 99-100 °C; [R]22 +11.0° (c 0.7, CHCl3); IR (neat,
D
cm-1) 3455, 2922, 1711, 1458, 1377; MS(FAB) m/z 935 (M +
K)+, 919 (M + Na)+, 879 (M - OH)+, 828 (M - Bn + Na)+;
HRMS(FAB) calcd for C55H58O11Na 919.4034, found 919.4035.
Anal. Calcd for C55H60O11: C, 73.64; H, 6.74. Found: C, 73.45;
H, 6.97.
Meth yl 2,3-d i-O-ben zyl-6-O-(2,3,4,6-tetr a -O-ben zyl-â-D-
m a n n o-p yr a n osyl)-r-D-ga la ctop yr a n osid e (17b): colorless
syrup; [R]24D -13.6° (c 1.2, CHCl3); IR (neat, cm-1) 3350, 2927,
1460, 1377; MS(FAB) m/z 935 (M + K)+, 919 (M + Na)+, 828
(M - Bn + Na)+; HRMS(FAB) calcd for C55H58O11Na 919.4034,
found 919.4045.
Meth yl 2,3-d i-O-ben zyl-4-O-(2,3,4,6-tetr a -O-ben zyl-â-D-
glu co-pyr an osyl)-r-D-glu copyr an oside (9b): colorless needle;
mp 132.5-134 °C; [R]24D +19.6° (c 1.0, CHCl3); IR (KBr, cm-1
)
Meth yl 2,3-d i-O-ben zyl-6-O-(2,3,4-tr i-O-ben zyl-â-D-fu -
copyr an osyl)-r-D-galactopyr an oside (18b): colorless needle;
mp 85-87 °C; [R]22D +10.3° (c 0.9, CHCl3); IR (neat, cm-1) 3409,
2926, 2855, 1460, 1377; MS(FAB) m/z 829 (M + K)+, 813 (M
3474, 2926, 2901, 2870, 1497, 1454, 1402, 1363; MS(FAB) m/z
935 (M + K)+, 919 (M + Na)+, 879 (M - OH)+, 828 (M - Bn
+ Na)+. Anal. Calcd for C55H60O11: C, 73.64; H, 6.74. Found:
C, 73.58; H, 6.74.
+ Na)+, 722 (M - Bn + Na)+; HRMS(FAB) calcd for C48H54O10
-
Meth yl 2,3-d i-O-ben zyl-4-O-(2,3,4,6-tetr a -O-ben zyl-â-D-
ga la ct o-p yr a n osyl)-r-D-glu cop yr a n osid e (10b ): colorless
needle; mp 145-146.5 °C; [R]26D +4.5° (c 1.0, CHCl3); IR (KBr,
cm-1) 3478, 2891, 2361, 2339, 1497, 1455, 1363; MS(FAB) m/z
935 (M + K)+, 919 (M + Na)+, 828 (M - Bn + Na)+. Anal.
Calcd for C55H60O11: C, 73.64; H, 6.74. Found: C, 73.61; H,
6.77.
Na 813.3615, found 813.3597, Anal. Calcd for C48H54O10: C,
72.89; H, 6.88. Found: C, 72.82; H, 7.04.
Meth yl 2,3-d i-O-ben zyl-6-O-(2,3,4-tr i-O-ben zyl-â-L-fu -
cop yr a n osyl)-r-D-glu cop yr a n osid e (13b): colorless syrup;
[R]22 +21.2° (c 1.5, CHCl3); IR (neat, cm-1) 3347, 2928, 1462,
D
1377; MS(FAB) m/z 829 (M + K)+, 813 (M + Na)+, 722 (M -
Bn + Na)+; HRMS(FAB) calcd for C48H54O10Na 813.3615, found
813.3628.
Meth yl 2,3-d i-O-ben zyl-4-O-(2,3,4,6-tetr a -O-ben zyl-â-D-
m a n n o-p yr a n osyl)-r-D-glu cop yr a n osid e (11b): colorless
syrup; [R]24D -14.3° (c 1.1, CHCl3); IR (neat, cm-1) 3464, 3031,
2924, 1605, 1497, 1455, 1364; MS(FAB) m/z 935 (M + K)+,
919 (M + Na)+, 828 (M - Bn + Na)+; HRMS(FAB) calcd for
Meth yl 2,3-di-O-ben zyl-6-O-(2,3,4-tr i-O-ben zyl-â-L-r h am -
n op yr a n osyl)-r-D-glu cop yr a n osid e (14b): colorless syrup;
[R]22 +53.7° (c 1.0, CHCl3); IR (neat, cm-1) 3376, 2926, 1711,
D
1458, 1377; MS(FAB) m/z 829 (M + K)+, 813 (M + Na)+, 722
(M - Bn + Na)+; HRMS(FAB) calcd for C48H54O10Na 813.3615,
found 813.3622.
C
55H58O11Na 919.4034, found 919.4015.
Meth yl 2,3-d i-O-ben zyl-4-O-(2,3,4-tr i-O-ben zyl-â-D-fu -
cop yr a n osyl)-r-D-glu cop yr a n osid e (12b): colorless syrup;
Meth yl 2,3-di-O-ben zyl-6-O-(2,3,4-tr i-O-ben zyl-r-L-r h am -
[R]22 +17.6° (c 0.7, CHCl3); IR (neat, cm-1) 3380, 2934, 2857,
n op yr a n osyl)-r-D-glu cop yr a n osid e (14c): colorless syrup;
D
1724, 1458, 1377; MS(FAB) m/z 829 (M + K)+, 813 (M + Na)+,
[R]25 -15.0° (c 1.1, CHCl3); IR (neat, cm-1) 3474, 3031, 2921,
D

Highly Stereoselective Construction of â-Glycosyl Linkages
J . Org. Chem., Vol. 65, No. 24, 2000 8179
1497, 1455, 1364; MS(FAB) m/z 829 (M + K)+, 813 (M + Na)+,
722 (M - Bn + Na)+; HRMS(FAB) calcd for C48H54O10Na
813.3615, found 813.3618.
(24). To a solution of 23a (506 mg 0.50 mmol) in EtOH (20
mL) was added ethylenediamine (5 mL).27 The mixture was
stirred for 6 h at 80 °C under Ar and then evaporated. The
residue was directly applied on a silica gel column (AcOEt/
hexane 1:1) to afford 24 as colorless needles (434 mg, 99%).
The analytical sample was obtained by recrystallization from
P r ep a r a tion of Glu cosa m in e Or th o Ester s. To a sus-
pension of lactone 1 (540 mg, 1.0 mmol) and diol 21 (489 mg,
1.0 mmol) in toluene (10 mL) was added TMSOMe (1.4 mL,
10 mmol) and TMSOTf (9 µL, 5 mol %) at room temperature
under Ar. After 1 h of stirring, the solvent was removed under
reduced pressure (5 mmHg, 1 h). The reaction vessel was
leaked with Ar, and the remainder was again dissolved in
toluene. TMSOMe (1.4 mL, 10 mmol) and TMSOTf (9 µL, 5
mol %) were added to the solution, and the mixture was stirred
for an additional 30 min. The solvent was removed under
reduced pressure again. The remainder was dissolved in CH2-
Cl2 containing 5% of Et3N and was applied to a silica gel
column (Et2O/hexane 1:2 then 1:1) to afford 23a as white solid
(865 mg, 86%). The ortho esters 23b and 23c were also
prepared from 1 and triol 22 according to the same procedure
in 10% and 74% yields, respectively. The latter ortho ester
(23c) was converted into the former one (23b) in 96% yield by
treating a methanol solution of K2CO3 (10mM) for 30 min at
room temperature.26 These three ortho esters were all crystal-
line compounds, and the needles of them were obtained by
recrystallization from Et2O/hexane.
Et2O/hexane: mp 109.5-111 °C; [R]25 +7.7° (c 1.1, CHCl3);
D
IR (neat, cm-1) 3031, 2917, 2870, 1455, 1356, 1207; MS(FAB)
m/z 919 (M + K)+, 903 (M + Na)+, 881 (M + H)+, 812 (M - Bn
+ Na)+. Anal. Calcd for C54H57NO10: C, 73.70; H, 6.53; N, 1.59.
Found: C, 73.88; H, 6.57; N, 1.67.
Ben zyl
3-O-Ben zyl-2-d eoxy-2-d iben zyla m in o-4,6-O-
(2,3,4,6-t et r a -O-b en zyl-D-glu cop yr a n osylid en e)-â-D-glu -
cop yr a n osid e (25). A mixture of 24 (87 mg 0.10 mmol), NaH
(60% in oil, 17 mg, 0.4 mmol), and benzylbromide (95 µL, 0.8
mmol) in DMF (4 mL) was stirred for 8 h at 60 °C under Ar.
The resulting mixture was extracted with AcOEt. The extract
was washed twice with water, dried over Na2SO4, and evapo-
lated. The residue was purified by silica gel column chroma-
tography (AcOEt/hexane 1:10, then 1:5) to afford 25 as
colorless syrup (99 mg, 94%): [R]25 +0.8° (c 1.5, CHCl3); IR
D
(neat, cm-1) 3395, 3063, 3031, 2924, 2867, 2361, 1495, 1455,
1362; MS(FAB) m/z 1099 (M + K)+, 1083 (M + Na)+, 1061 (M
+ H)+, 992 (M - Bn + Na)+; HRMS(FAB) calcd for C68H69
NO10 1060.5000, found 1060.4993.
-
Ben zyl 3-O-ben zyl-2-deoxy-2-ph th alim ido-4,6-O-(2,3,4,6-
tetr a -O-ben zyl-D-glu cop yr a n osylid en e)-â-D-glu cop yr a n o-
Ben zyl 3-O-Ben zyl-2-deoxy-2-diben zylam in o-4-O-(2,3,4,6-
t e t r a -O-b e n zyl-â-D-glu cop yr a n osyl)-â-D-glu cop yr a n o-
sid e (26). 25 (53 mg, 0.05 mmol) was reduced with LiAlH4 (4
mg, 0.1 mmol) and AlCl3 (13 mg, 0.1 mmol) according to the
procedure describe above to afford 26 as colorless syrup (43
sid e (23a ): colorless needle; mp 114-115 °C; [R]27 +34.9° (c
D
1.0, CHCl3); IR (neat, cm-1) 3486, 3031, 2915, 2361, 1781, 1717,
1455, 1389; MS(FAB) m/z 1049 (M + K)+, 1033 (M + Na)+,
942 (M - Bn + Na)+. Anal. Calcd for C62H59NO12: C, 73.72;
H, 5.89; N, 1.39. Found: C, 73.77; H, 5.95; N, 1.53.
mg, 82%): [R]22 -16.3° (c 0.8, CHCl3); IR (neat, cm-1) 3447,
D
Ben zyl 2-d eoxy-2-p h t h a lim id o-4,6-O-(2,3,4,6-t et r a -O-
ben zyl-D-glu copyr an osyliden e)-â-D-glu copyr an oside (23b):
3063, 3031, 2923, 2867, 1495, 1455, 1360; MS(FAB) m/z 1101
(M + K)+, 1085 (M + Na)+, 1063 (M + H)+, 994 (M - Bn +
Na)+; HRMS(FAB) calcd for C68H71NO10 1062.5156, found
1062.5145.
colorless needle; mp 65-66.5 °C; [R]25 +4.2° (c 1.0, CHCl3);
D
IR (neat, cm-1) 3482, 3031, 2923, 2361, 1777, 1717, 1455, 1389;
MS(FAB) m/z 959 (M + K)+, 943 (M + Na)+, 921 (M + H)+,
852 (M - Bn + Na)+. Anal. Calcd for C55H53NO12: C, 71.80;
H, 5.81; N, 1.52. Found: C, 71.66; H, 5.92; N, 1.64.
Ack n ow led gm en t. We are grateful to Misses J .
Shimode, J . Nonobe and M. Kitsukawa for spectroscopic
measurements. Partial financial support for this re-
search from the Ministry of Education, Science, Sports
and Culture of J apan is gratefully acknowledged.
Ben zyl 2-d eoxy-2-p h t h a lim id o-4,6-O-(2,3,4,6-t et r a -O-
b en zyl-D-glu cop yr a n osylid en e)-3-O-t r im et h ylsilyl-â-D-
glu cop yr a n osid e (23c): colorless needle; mp 93.5-94.5 °C;
[R]24 +4.1° (c 1.0, CHCl3); IR (neat, cm-1) 3031, 2923, 1777,
D
1717, 1455, 1389, 1252; MS(FAB) m/z 1031 (M + K)+, 1015
(M + Na)+, 993 (M + H)+, 924 (M - Bn + Na)+. Anal. Calcd
for C58H61NO12Si: C, 70.21; H, 6.20; N, 1.41. Found: C, 70.46;
H, 6.32; N, 1.51.
Su p p or tin g In for m a tion Ava ila ble: Peak assignments
in 1H NMR and 13C NMR spectra for 9b-20b, 14c, 23a , 23b,
23c, and 24-26. This material is available free of charge via
the Internet at http://pubs.acs.org.
Ben zyl 2-Am in o-3-O-ben zyl-2-deoxy-4,6-O-(2,3,4,6-tetr a-
O-b en zyl-D-glu cop yr a n osylid en e)-â-D-glu cop yr a n osid e
J O0005870