Glycosylation via locked anomeric configuration: Stereospecific synthesis of oligosaccharides containing the β-D-mannopyranosyl and β-L- rhamnopyranosyl linkage

Article abstract of DOI:10.1016/S0008-6215(98)00057-3

cis-1,2-Stannylene acetals of D-mannose and L-rhamnose, formed preferentially from the free sugars treated with dibutyltin oxide, are capable of displacing the trifluoromethanesulfonyl (triflyl) leaving groups in carbohydrates to give, with retention of configuration at the anomeric center in the nucleophile, cis-1,2-linked oligosaccharides. In the case of secondary triflates, the new glycosidic linkage is formed with complete inversion of configuration in the electrophile. Both the reactivity of the electrophile and nucleophilicity of oxygens in the stannylene complex affect the overall outcome of the reaction. From the comparison of results of a number of glycosylations via stannylene acetals, it appears that nucleophilicity of oxygens involved in the cis-1,2-acetals decreases in the order: equatorial anomeric > equatorial non-anomeric > axial anomeric. Consequently, treatment of the stannylene acetal prepared from D-mannose (mainly the cis-1,2-stannylene compound in admixture with a small proportion of the cis-2,3-stannylene acetal) with methyl 2,3,4-tri-O-benzoyl-6-O- trifluoromethanesulfonyl-α-D-glucopyranoside yielded, in addition to the expected β-D-mannopyranoside (major), a product of non-anomeric alkylation at O-3. On the other hand, glycosylation of the stannylene acetal derived from maltose with methyl 2,3,6-tri-O-benzoyl-4-O-trifluoromethanesulfonyl- α-D-galactopyranoside gave almost exclusively a nonglycosidically, (2→4)- linked pseudo-trisaccharide. Combination of the glycosylation via locked anomeric configuration with conventional glycosylations, to yield higher oligosaccharides, is also demonstrated.

Full text of DOI:10.1016/S0008-6215(98)00057-3

Carbohydrate Research 308 (1998) 63±75
Glycosylation via locked anomeric con®guration:
stereospeci®c synthesis of oligosaccharides
containing the ꢀ-d-mannopyranosyl and
ꢀ-l-rhamnopyranosyl linkage1
Gyorgy Hodosi, Pavol Kovac *
NIDDK, National Institutes of Health, 8 Center Drive, Bethesda, MD 20892-0815, USA
Received 11 December 1997; accepted 26 February 1998
Abstract
cis-1,2-Stannylene acetals of d-mannose and l-rhamnose, formed preferentially from the free
sugars treated with dibutyltin oxide, are capable of displacing the tri¯uoromethanesulfonyl (tri¯yl)
leaving groups in carbohydrates to give, with retention of con®guration at the anomeric center in
the nucleophile, cis-1,2-linked oligosaccharides. In the case of secondary tri¯ates, the new glyco-
sidic linkage is formed with complete inversion of con®guration in the electrophile. Both the
reactivity of the electrophile and nucleophilicity of oxygens in the stannylene complex a€ect the
overall outcome of the reaction. From the comparison of results of a number of glycosylations via
stannylene acetals, it appears that nucleophilicity of oxygens involved in the cis-1,2-acetals
decreases in the order: equatorial anomeric > equatorial non-anomeric > axial anomeric. Con-
sequently, treatment of the stannylene acetal prepared from d-mannose (mainly the cis-1,2-stan-
nylene compound in admixture with a small proportion of the cis-2,3-stannylene acetal) with
methyl 2,3,4-tri-O-benzoyl-6-O-tri¯uoromethanesulfonyl-ꢁ-d-glucopyranoside yielded, in addition
to the expected ꢀ-d-mannopyranoside (major), a product of non-anomeric alkylation at O-3. On
the other hand, glycosylation of the stannylene acetal derived from maltose with methyl 2,3,6-tri-
O-benzoyl-4-O-tri¯uoromethanesulfonyl-ꢁ-d-galactopyranoside gave almost exclusively a non-
glycosidically, (2!4)-linked pseudo-trisaccharide. Combination of the glycosylation via locked
anomeric con®guration with conventional glycosylations, to yield higher oligosaccharides, is also
demonstrated. # 1998 Elsevier Science Ltd. All rights reserved
Keywords: Stereospeci®c ꢀ-d-mannosylation ; Stereospeci®c ꢀ-l-rhamnosylation ; cis-1,2-O-stannylene acet-
als ; Stereospeci®c glycosylation ; Oligosaccharide synthesis
1. Introduction
the interest in synthetic oligosaccharides [1,2].
Thus, the e€orts to develop new methods for the
synthesis of oligosaccharides, chemical or chemo-
enzymatic, have escalated during the past decade
[3±5]. Of the many, principally diverse methods
available for oligosaccharide synthesis, most e-
cient are those where the stereochemical outcome
of the reaction is facilitated by neighboring group
The involvement of oligosaccharide structures in
vital biological processes has markedly increased
* Corresponding author. Fax: (301) 402-0589; e-mail:
kpn@helix.nih.gov
1
For a preliminary account of this work, see ref. 7.
0008-6215/98/$19.00 # 1998 Elsevier Science Ltd. All rights reserved
PII S0008-6215(98)00057-3

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
64
participation. While the latter methods work very
satisfactorily to synthesize trans-1,2-glycosides/oli-
gosaccharides, the synthesis of their cis-counter-
parts, particularly ꢀ-l-rhamno- and ꢀ-d-manno-
linked oligosaccharides, is still a formidable task
[6]. Recently, we reported [7] on a fundamentally
new method for the stereospeci®c synthesis of the
ꢀ-l-rhamno- and ꢀ-d-mannopyranosyl linkage. It
is based on the increased nucleophilicity of the
anomeric oxygen, when it becomes part of a stan-
nylene acetal. Formally, the method involves
anomeric alkylation, pioneered by Schmidt and his
co-workers [8±10]. In our case, contrary to the lat-
ter approach where the sodium salt of the anomeric
hydroxyl group is present in both ꢁ- and ꢀ-forms,
the anomeric oxygen is conveniently locked in the
the anomeric oxygen as the nucleophile, can be
obtained from such a mixture only if the 1,2-O-
acetal predominates. Therefore, the objective of
our initial treatments of unprotected sugars with 3
was to ascertain the nature of stannylene acetals
present when the equilibrium among possible iso-
mers is reached. The presence of a high proportion
of 4 in the product after treatment of l-rhamnose
(1) with 3 was indicated when subsequent acetyla-
tion yielded [11] the ꢀ-per-O-acetyl derivative in
>80% yield. The same was con®rmed by NMR
spectral data obtained [11] for the product of the
stannylation of l-rhamnose (1). Other important
information obtained during that work was that
the formation of stannylene acetals from free
sugars may be accompanied by epimerization, and
that the extent of that side reaction can be con-
trolled [11]. Having been able to minimize the
occurrence of epimerization by conducting the
acetal-forming reaction with a limited amount of
the reagent under mild conditions [11,14], we
turned our attention to replacement of leaving
groups in carbohydrates using 1,2-O-stannylene
acetals as nucleophiles. No reaction was observed
([15], TLC) when 6-deoxybromo, or 6-deoxyiodo
derivatives of d-mannose (2), or the correspond-
ing mesylate, were treated with 1,2-O-stannylene
1
1,2-cis con®guration. We have con®rmed by H
and 13C NMR spectroscopy [11] that the acetal
preferentially formed from l-rhamnose treated
with dibutyltin oxide is, indeed, the cis-1,2-acetal.
Consequently, while classical anomeric alkylation
normally yields a mixture of anomers, our manno-
sylation or rhamnosylation via locked anomeric
con®guration a€ords, stereospeci®cally, the cis-1,2-
oligosaccharides.
The concept of using cis-1,2-stannylene acetals
of otherwise protected sugars for simple anomeric
alkylations with alkyl halides has been previously
used [12,13]. Our approach [7] extends the use of
1,2-stannylene acetals to a simple, high yielding,
stereospeci®c synthesis of the ꢀ-d-mannopyranosyl
and ꢀ-l-rhamnopyranosyl linkages, and is superior
to previous protocols in that protection of hydroxyl
groups in sugars to be converted to stannylene
acetals is not required.
The present paper describes the scope and lim-
itations of the new method, experimental details
for preparations reported in our recent short com-
munication [7], and full characterization of rele-
vant substances synthesized. Also, we demonstrate
the potential the new method has, in combination
with conventional glycosylation techniques, in
syntheses of more complex oligosaccharides.
acetals,
but
the
use
of
the
tri-
¯uoromethanesulfonyl (tri¯yl) leaving group was
successful. When necessary, the solubility of stan-
nylene complexes could be enhanced by addition
of CsF or phase-transfer salts, e.g., Bu4NF, to
reaction mixtures.
Initially, we tried the anomeric alkylation of the
cis-1,2-stannylene acetal of l-rhamnose (4) with
the primary tri¯ate 7, prepared from 6 [16] by the
method of Ambrose and Binkley [17] (Scheme 1).
When the reaction was conducted at ambient
temperature in DMF as the solvent, the yield of the
desired ꢀ-l-rhamnoside 10 was ꢀ50%. As a result
of a reaction between tri¯ate 7 and DMF, formate
8 was also produced, and it was isolated in a yield
of ꢀ25%. The formation of this unwanted side
product could be minimizedꢁwhen the same reac-
tion was performed at 5 C. The yield of the
target disaccharide 10 increased then to 88%. In
these reactions, the readily available dibutyltin
acetal of l-rhamnose (4) was used in large excess
(4±6 equivalents). This enhanced the rate of the
desired alkylation, thereby largely avoiding the
accompanying side reaction of the starting tri-
¯ate.
2. Results and discussion
When an unprotected sugar, e.g., mannose (2) or
rhamnose (1), is treated with one equivalent of
dibutyltin oxide (3) isomeric acetals may be
formed. Thus, a high yield of the ꢀ-product,
resulting from a displacement reaction involving

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
65
The stannylene acetal 4 also reacted smoothly
with the less reactive secondary tri¯ate 9 [18]. The
extent of formylation at the secondary position in 9
was minimalꢁ even when the reaction was con-
ducted at 25 C and, after a reaction time of 2.5 h,
the desired disaccharide 11 was obtained in 78%
yield. This is a notable improvement compared to
the highest yield of the ꢀ-l-Rha-(1!4)-d-Glc link-
age reported thus far (43%) [19].
Reactions of the analogous tin acetal 5 prepared
from d-mannose (2) were less successful. The ꢀ-
linked disaccharide 12, formed from tri¯ate 7,
could be obtained only in 40%, together with a by-
product 20 (Scheme 2) isolated in 23% yield. The
Scheme 1.

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
66
Scheme 2.
mass spectrum of 20 showed a pseudomolecular
ion peak at m/z 686, showing that the compound
was isomeric with the desired ꢀ-mannoside 12.
Compound 20, an ꢁ,ꢀ-mixture, was treated with
pyridine±Ac2O, and characterized as the corre-
sponding peracetate 21. That 20 was not the ꢁ-
linked isomer of 12, but the product of non-
anomeric alkylation at position-3 of the mannose
residue, followed from the analysis of spectral data
obtained for 21. The 13C NMR spectrum showed
only one signal at 60±65 ppm, showing that the
tri¯yl group has undergone a substitution reaction.
In agreement with this ®nding, the signal for C-6I
appeared down®eld (ꢂ 68.80). In the anomeric
region of the 13C NMR spectrum of the substance
there were two signals, one of which (ꢂ 96.77, JC,H
172.9 Hz) showed chemical shift similar to that of
C-1I of 12. This, together with the chemical shifts
of other ring carbons of the glycoside residue,
which were found to be close to those present in
the 13C NMR spectrum of 12 (see Experimental),
indicated that the aglycon bearing residue of the
main product 12 and 21 are virtually identical. The
other signal in the anomeric region of the 13C
NMR spectrum of 21 appeared at ꢂ 90.93 (JC,H
177.2 Hz), indicating that the anomeric position of
the second sugar ring was not involved in an inter-
glycosidic linkage but was acetylated. Structure 21,
i.e., per-O-acetylated-ꢁ-d-mannopyranose linked
ethereally through its position-3 to position-6 of
methyl 2,3,4-tri-O-benzoyl-ꢁ-d-glucopyranoside,
was corroborated by its 2D 1H±13C correlated
(HETCOR) spectrum. There, the ring 13C signal
appearing at the lowest ®eld, indicative of its
involvement in an ether linkage, showed a cross-
peak with H-3 of the per-O-acetylated mannose
residue. A plausible explanation for the formation
of 20 from 5 and 7 is the isomerisation of the cis-
1,2-acetal 5 into cis-2,3-acetal 19, thus activating
the oxygen at C-3 in d-mannose, which becomes a
competing nucleophile in the substitution reaction.
The yield and the ratio of products of the reaction
5+7!12+20 was found to be solvent dependent.
When N,N-dimethylacetamide (DMA) was used

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
67
[15], the products 12 and 20 were formed in a ratio
of ꢀ1:1 (TLC). This indicates, ®rstly, that the iso-
merisation of 5 to 19 is solvent dependent and,
secondly, that in solvents of higher dielectric con-
stants the di€erence between the nucleophilicity of
equatorial anomeric and a non-anomeric oxygens
diminishes. The best yield of 12 (57%) was
obtained when the reaction 5+7 was performed in
acetonitrile in the presence of Bu4NF. The e€ect of
solvent upon the outcome of the reaction of the
secondary tri¯ate 9 could be further demonstrated
in the series of experiments involving di€erent sol-
vents (for a tabular presentation of results
obtained, see ref [7].). As the polarity of the solvent
increased, the reactivity of reactants and, conse-
quently, the yield of the desired SN2 reaction
increased as well. Thus, when reactions were con-
The successful preparation of the partially ben-
zylated disaccharide 16 prompted us to explore the
feasibility of application of the new glycosylation
technique to synthesizing more complex oligo-
saccharides, by combination with conventional
glycosylation methods. A suitable glycosyl accep-
tor 18 was obtained from 16 by perbenzoylation
(!17), followed by hydrogenolytic cleavage of the
benzyl group. Compound 18 was glycosylated
using lactosyl imidate 28 [20] in the presence of
.
BF3 etherate a€ording the tetrasaccharide 29 in
70% yield.
In order to explore the utility of the glycosyla-
tion via locked anomeric con®guration to syn-
thesizing cis-1,2-oligosaccharides in the gluco
series, we prepared the 1,2-stannylene complex of
maltose (30) (Scheme 3) and treated it with tri¯ate
9 under conditions proven favorable in similar
situations (vide supra). The major product formed
under these conditions was an ꢁ,ꢀ-mixture of the
(2!4)-linked pseudo-oligosaccharide 31. This
showed that when the equatorially oriented oxy-
gen at C-2 becomes part of the cis-1,2-stannylene
acetal, it becomes a stronger nucleophile than
the similarly engaged, axially oriented anomeric
oxygen.
ꢁ
ducted at 25 C, the yield of the disaccharide 15
was 40% in DMF as solvent after 5 days, 53% in
DMA after 3 days, and 59% in DMSO after 2
days. The above-mentioned isomerisation of 5 into
19 could be completely eliminated when the 1,2-
stannylene acetal 13 of 3-O-benzyl-d-mannose (27)
was used as the nucleophile. Accordingly, reactions
of 13 with tri¯ates 7 and 9, gave the ꢀ-linked dis-
accharides 14 and 16 in increased yields of ꢀ-man-
nopyranosyl linkages (ꢀ73 and 67%, respectively).
The mannose derivative 27 used in the foregoing
experiments was obtained as follows. The 2,3-
stannylene acetal of methyl ꢁ-d-mannopyranoside
(22) was benzylated a€ording 23 (ꢀ73%). The lat-
ter was subjected to acetylation/acetolysis (!24,
90%), and subsequent deacetylation of 24 then
gave the target 3-O-benzyl derivative 27.
The isomerisation 5!19 suggested above is evi-
dent from the results of alkylation of 5 with benzyl
bromide. In addition to unchanged d-mannose,
and benzyl 3-O-benzyl-ꢀ-d-mannopyranoside (25,
18%), the main product was a 1.2:1 mixture of 3-
O-benzyl-d-mannose (27) and benzyl ꢀ-d-manno-
pyranoside (26, ꢀ40%; since the latter mixture
could be only partially resolved by chromato-
graphy, the structure and the ratio of components
were established by NMR spectroscopy). Again,
formation of 25 and 27 must have been preceded
by isomerisation of the cis-1,2-acetal 5 into the cis-
2,3-acetal 19. When a solution of 5 in DMA was
kept overnight at 25 ꢁC and then subjected to
similar benzylation [15], the ratio of 27 to 26
formed was only slightly changed, to 1.5:1. This
indicates that the isomerisation is a much faster
process than the alkylation itself.
To elucidate the structure of the product 31
resulting from attempted glycosylation with 30 as
the glycosyl donor, the pure material isolated by
chromatography was acetylated. An ꢁ,ꢀ-mixture
was formed, and the ꢀ-1-O-acetyl derivative 32 was
isolated in admixture with a small proportion
(ꢀ10%) of the ꢁ-isomer. The mass spectral and
NMR characteristics observed for such material
showed that it was isomeric with the desired tri-
saccharide. The diagnostically signi®cant observa-
tions supporting the presence of the O-2!O-4-
ether linkage in 32, rather than the (1!4)-glycosi-
dic linkage expected to be present in the targeted
trisaccharide, follow (for complete 1H and 13C
NMR data, see Experimental): The CIMS spec-
trum contained a quasi molecular ion peak at m/z
1142. That the nucleophilic substitution at posi-
tion-4 in compound 9 had occurred with inversion
of con®guration was evident from the appearance
of H-4I signal as a triplet (J 10.1 Hz), as would be
expected for the axially oriented H-4 proton in a d-
glucose residue interacting with two axially orien-
1
ted protons at C-3 and C-5. Also, in the H NMR
spectrum of 32, the doublet of H-1II appears
down®eld (ꢂ 5.61, J1,2 7.5 Hz) as expected for signal
of a proton which is part of a CH3CO±O±C±H

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
68
Scheme 3.
group, showing that position to be acetylated. At
the same time, the 13C signal for C-2II and C-4I
appeared down®eld (ꢂ 76.87 and 75.32, respec-
tively) as is common for ring carbons in carbohy-
drates that are engaged in an interglycosidic
linkage.
nated d-glucose residue, showing that position not
to be involved in an interglycosidic linkage, but
that it was acetylated. The high-®eld signal found
for H-2 of the same moiety showed that that pro-
ton was not part of an H±C±OCOCH3 group.
1
This, together with the cross-peak in the H±13C
Finally, when the 1,2-stannylene derivative pre-
pared from 4,6-O-benzylidene-d-glucose (33) was
treated with tri¯ate 7, the main product was the ꢀ-
Glc-(1!6)-Glc disaccharide 35, isolated in 57%
yield. A small amount of a byproduct was also
formed and isolated by chromatography. The
pseudomolecular ion peak present in the CI mass
spectrum of this material indicated that it could be
methyl 4,6-O-benzylidene-ꢁ,ꢀ-d-glucopyranos-2-
yl-(2!6)-2,3,4-tri-O-benzoyl-ꢁ-d-glucopyranoside
(34), a compound isomeric with 35. Mass spectral
analysis of the substance formed from 34 upon
heteronuclear correlation NMR spectrum showing
connectivity between H-2II and the 13C signal
appearing at ꢂ 80.19, provided concluding evidence
that the material was the (2!6)-ether linked sub-
stance 36, analogous to the ether-type pseudodi-
saccharides obtained from similar reactions. The
explanation for the formation of 34 and 35 is not
straightforward. It is not inconceivable, however,
that in the most stable conformation of the 1,2-O-
stannylene acetal of compound 33, the orientation
of the anomeric oxygen is close to equatorial, and
then the two equatorially oriented oxygen atoms,
O-1 and O-2, that are part of the stannylene acetal
are competing species in displacing the leaving
group in the electrophile.
1
acetylation, 36, supported the same. The H NMR
spectrum of 36 showed (see Experimental) low-®eld
signals for anomeric protons of the O-benzylide-

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
69
3. Experimental
J 10.0 Hz, H-3), 5.80 (t, 1 H, J 10.0 Hz, H-4), 5.46
(dd, 1 H, J1,2 3.7, J2,3 10.4 Hz, H-2), 5.16 (d, 1 H,
H-1), 4.20 (d, 2 H, H-6a,b), 4.10 (m, 1 H, H-5),
2.97 (s, 3 H, OCH3); 13C NMR (CDCl3): ꢂ 159.98
(HC=O), 97.44 (C-1), 72.42 (C-2), 70.99 (C-3),
69.94 (C-4), 67.92 (C-5), 61.76 (C-6), 55.23
(OCH3); CIMS: m/z 552 ([M+18]+).
Unless stated otherwise, optical rotations were
measured at ambient temperature for solutions in
chloroform (cꢀ1), with a Perkin±Elmer automatic
polarimeter, Model 241 MC, or Model 341. All
reactions were monitored by thin-layer chromato-
graphy (TLC) on glass slides coated with Silica Gel
60 (Whatman or Analtech), with solvent mixtures
of appropriately adjusted polarity consisting of
components listed in the Experimental. Column
chromatography was performed by gradient elu-
tion from columns of silica gel. Solvent mixtures
slightly less polar than those used for TLC were
used at the onset of development. Assignments of
NMR signals were made by ®rst-order analysis of
the spectra, and, when feasible, the assignments
were supported by homonuclear decoupling
experiments or homonuclear and heteronuclear 2-
dimensional correlation spectroscopy, run with the
software supplied with the spectrometers. When
reporting assignments of NMR signals, sugar resi-
dues in oligosaccharides are serially numbered,
beginning with the one bearing the methyl agly-
cone, and are identi®ed by a Roman numeral
superscript in listings of signal assignments. 4,6-O-
Benzylidene-d-glucose was purchased from Sigma
Chemical Company. Unless indicated otherwise,
solutions in organic solvents were dried with
anhydrous Na2SO4 and concentrated at 40 ꢁC/
2 kPa.
Second eluted was 10 (0.06 g, 49.2%): mp 150.5±
ꢁ
ꢁ
1
151.5 C (from EtOH), [ꢁ]d+126.6 . H NMR
(CDCl3): ꢂ 6.13 (t, 1 H, J 9.7 Hz, H-3I), 5.74 (t, 1
H, J 9.9 Hz, H-4I), 5.31±5.24 (m, 2 H, H-1I,2I), 4.52
(bs, 1 H, H-1II), 4.25 (dbt, 1 H, H-5I), 4.13 (dd, 1
H, J5,6 3.9, J5 ,6b 11.4 Hz, H-6aI), 4.00 (bd, 1 H,
a
a
H-2II), 3.78 (dd, 1 H, J5, 2.3 Hz, H-6bI), 3.46 (s, 3
6b
H, OCH3), 3.43±3.40 (m, 2 H, H-3II,4II), 3.22±3.13
(m, 1 H, H-5II), 1.07 (d, 3 H, J5,6 6.1 Hz, H-6II);
13C NMR (CDCl3): ꢂ 99.13 (C-1II, JC,H 157.8 Hz),
97.20 (C-1I, JC,H 172.7 Hz), 74.17 (C-3II), 72.92 (C-
4II), 72.15 (C-2I), 71.79 (C-5II), 70.52 (2 C, C-
3I,2II), 68.98 (C-4I), 68.41 (C-5I), 66.11 (C-6I),
55.70 (OCH3), 17.02 (C-6II); CIMS: m/z 670
([M+18]+). Anal Calcd for C34H36O13 H2O: C,
.
61.72; H, 5.64. Found: C, 61.89; H, 5.61.
(b) A mixture of l-rhamnose (1, 0.713 g,
3.92 mmol) and dibutyltin oxide (3, 0.877 g,
3.52 mmol) in anhyd methanol (25 mL) was stirred
ꢁ
at 60 C (bath) until a clear solution was obtained
(ꢀ1.5 h). CsF (0.714 g, 4.7 mmol) and toluene
(5 mL) were added, and the mixture was con-
cenꢁtrated. The residue, after having been kept at
50 C/0.3 kPa for 2.5 h to assure dryness, was dis-
solved in DMF (5 mL), molecular sieves (4 A, 0.5 g)
were added, and the solution was cooled to 5 ꢁC.
After addition of 7 (0.5 g, 0.79ꢁmmol), the mixture
was stirred vigorously at 5 C for 80 min, and
concentrated. The residue was triturated with
acetonitrile, the resulting suspension was ®ltered
through a pad of Celite, the solids were washed
with acetonitrile, and the combined ®ltrate was
concentrated. Chromatography of the residue gave
10 (0.45 g, 88.2%).
Methyl
2,3,4-tri-O-benzoyl-6-O-formyl-a-d-
glucopyranoside (8) and methyl b-l-rhamno-
pyranosyl-(1!6)-2,3,4-tri-O-benzoyl-a-d-glucopy-
ranoside (10).Ð(a) A mixture of l-rhamnose
monohydrate (1, 0.114 g, 0.628 mmol) and dibu-
tyltin oxide (3, 0.152 g, 0.612 mmol) in anhyd
methanol (3 mL) was stirred at 70 ꢁC (bath) until a
clear solution was obtained (ꢀ35 min). Toluene
(1 mL) was added, and the mixture was con-
centrated. The residue, after having been kept at
ꢁ
50 C/2 kPa for 2.5 h to assure dryness, was dis-
solved in DMF (2 mL). After addition of 7 (0.1 g,
Methyl b-l-rhamnopyranosyl-(1!4)-2,3,6-tri-O-
benzoyl-a-d-glucopyranoside (11).ÐA mixture of
l-rhamnose (1, 0.713 g, 3.92 mmol) and dibutyltin
oxide (3, 0.877 g, 3.52 mmol) in anhyd methanol
0.157 mmol), the mixture was stirred vigorously at
ꢁ
20 C for 2 h, and concentrated. The residue was
ꢁ
triturated with acetonitrile, the resulting suspen-
sion was ®ltered through a pad of Celite, solids
were washed with acetonitrile, and the combined
®ltrate was concentrated. Chromatography
(dichloromethane±methanol) of the residue gave
®rst the largely unstable 8 (0.03 g, 24.6%). 1H
NMR (C6D6): ꢂ 7.58 (s, 1 H, CH=O), 6.60 (t, 1 H,
(25 mL) was stirred at 60 C until a clear solution
was obtained (ꢀ1.5 h). CsF (0.714 g, 4.7 mmol) and
toluene (5 mL) were added, and the mixture was
concentrated. The residue, after having been kept
ꢁ
at 50 C/0.2 kPa, for 2.5 h, was dissolved in DMF
(5 mL), and molecular sieves (4 A, 0.5 g) were
added. After addition of 9 (0.5 g, 0.79 mmol), the

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
70
mixture was stirred vigorously at 20 ꢁC for 140 min
and then concentrated. The residue was triturated
with acetonitrile, the resulting suspension was ®l-
tered through a pad of Celite, the solids were
washed with acetonitrile, and the combined ®ltrate
was concentrated. Chromatography gave 11 (0.4 g,
78.4%): [ꢁ]d+142.0 . H NMR (CDCl3): ꢂ 6.03
(dd, 1 H, J3,4 8.8, J4,5 10.3 Hz, H-3I), 5.22 (dd, 1 H,
J1,2 3.4, J2,3 10.3 Hz, H-2I), 5.15 (d, 1 H, H-1I), 4.74
(bd, 1 H, H-6Ia), 4.66 (dd, J5,6 4.0, J6a,6b 12.0 Hz,
H-6Ib), 4.48 (s, 1 H, H-1II), 4.22±4.13 (m, 2 H, H-
4I,5I), 3.68 (bd, 1 H, J2,3 ꢀ3.1 Hz, H-2II), 3.40 (s, 3
H, OCH3), 3.32 (t, 1 H, J 9.3 Hz, H-4II), 3.08±3.00
(m, 2 H, H-3II,5II), 1.12 (d, 3 H, J5,6 6.1 Hz, H-6);
13C NMR (CDCl3): ꢂ 100.20 (C-1II, JC,H 156.5 Hz),
96.85 (C-1I, JC,H 170.8 Hz), 74.81 (C-4I), 73.90 (C-
3II), 72.65 (C-3I), 72.55 (C-4II), 72.08 (C-5II), 71.66
(C-2I), 70.70 (C-2II), 68.48 (C-5I), 63.42 (C-6I),
55.30 (OCH3), 17.04 (C-6II); CIMS: m/z 670
([M+18]+). Anal. Calcd for C34H36O13: C, 62.57;
H, 5.56. Found: C, 62.33; H, 5.61.
solved in anhyd DMF (2.0 mL), and molecular
sieves (4 A, 0.2 g) were added. After addition of 7
(0.19 g, 0.298 mmol), the mixture was stirred vig-
ꢁ
orously at 0 C for 4 h and then concentrated. The
residue was triturated with acetonitrile, the result-
ing suspension was ®ltered through a pad of Celite,
the solids were washed with acetonitrile, and the
combined ®ltrate was concentrated. Chromato-
graphy (CH2Cl2±MeOH) gave ®rst 20 0.045 g,
22.6%) as mixture of ꢁ- and ꢀ-anomers, m/z 686
([M+18]+).
ꢁ
1
For characterization, the material wasꢁacetylated
with acetic anhydride in pyridine at 20 C to give,
after column chromatography (hexane±ethyl acet-
ate, pure 21: [ꢁ]d+56ꢁ. H NMR (CDCl3): ꢂ 6.12
1
(dd, 1 H, J2,3 10.0, J3,4 9.5 Hz, H-3I), 6.06 (d, 1 H,
J1,2 2.0 Hz, H-1II), 5.43 (dd, 1 H, J4,510.4 Hz, H-4I),
5.30 (t, partially overlapped, J ꢀ10.0 Hz, H-4II),
5.29 (dd, partially overlapped, H-2II), 5.23 (dd, 1
H, J1,2 3.5, J2,3 10.0 Hz, H-2I), 5. 17 (d, 1 H, H-1I),
4.26 (dd, 1 H, J5,6a 5.1, J6a,6b 12.4 Hz, H-6IIa), 4.10
(dd, partially overlapped, J5,6b 2.4 Hz, H-6IIb), 4.08
(m, partially overlapped, H-5I), 3.96 (ddd, 1 H, H-
5II), 3.87 (dd, partially overlapped, J2,3 3.5 Hz, H-
3II), 3.82 (dd, partially overlapped, H-6Ia), 3.58
(dd, 1 H, J5,6b 6.0 Hz, H-6Ib), 3.43 (s, 3 H, OCH3),
Methyl b-d-mannopyranosyl-(1!6)-2,3,4-tri-O-
benzoyl-a-d-glucopyranoside (12) and methyl 2,3,4-
tri-O-benzoyl-6-O-(1,2,4,6-tetra-O-acetyl-a-d-gluco-
pyranos-3-yl)-a-d-glucopyranoside
(21).ÐTri¯ic
anhydride (1.2 mL, 7.1 mmol) was added at 20 ꢁC
to a stirred solution of methyl 2,3,4-tri-O-benzoyl-ꢁ-
d-glucopyranoside [16] (6, 3.0 g, 5.92mmol) and 2,4-
di-tert-butyl-4-methylpyridine (1.82 g, 8.88mmol) in
anhyd CH2Cl2 (30 mL), and the mixture was kept
at the same temperature for 2 h. After concentra-
tion, the residue was triturated with ether, and the
solids were ®ltered o€ and washed with ether. The
combined ®ltrates were concentrated, and the resi-
due was chromatographed to give methyl 2,3,4-tri-
O-benzoyl-6-O-tri¯uoromethanesulfonyl-ꢁ-d-glu-
copyranoside (7) that was used immediately for the
next step. 1H NMR (CDCl3): ꢂ 6.19 (m, 1 H, H-3),
5.47 (t, 1 H, J 9.8 Hz, H-4), 5.30±5.26 (m, 2 H, H-
1,2), 4.69 (dd, 1 H, J5,6a 6.6, J6a,6b 11.3 Hz, H-6a),
4.62 (dd, 1 H, J5,6b 2.3 Hz, H-6b), 4.38 (ddd, 1 H,
H-5), 3.50 (s, 3 H, OCH3); 13C NMR (CDCl3): ꢂ
97.11 (C-1), 73.93 (C-6), 71.60 (C-2), 69.87 (C-3),
69.03 (C-4), 67.50 (C-5); CIMS: m/z 656
([M+18]+).
2.14, 2.13, 2.12, 2.09 (4 s, 3 H each, 4 COCH3); 13
C
NMR (CDCl3): ꢂ 96.77 (C-1I, JC,H 172.9 Hz), 90.93
(C-1II, JC,H 177.2), 75.91 (C-3II), 72.05 (C-2I),
70.68 (C-5II), 70.50 (C-3I), 69.25 (C-4I), 69.00 (C-
5I), 68.80 (C-6I), 67.08 (C-2II), 66.96 (C-4II), 62.36
(C-6II), 55.36 (OCH3); CIMS: m/z 855 ([M+18]+).
Anal. Calcd for C42H44O18: C, 60.28; H, 5.30.
Found: C, 60.01 ; H, 5.39.
Later eluted was 12 (0.08 g, 40.2%) [ꢁ]d+30.2ꢁ;
1H NMR (CDCl3+D2O): ꢂ 6.13 (t, 1 H, J 9.7 Hz,
H-3I), 5.65 (t, 1 H, J 9.7, H-4I), 5.31±5.22 (m, 2 H,
H-1I,2I), 4.47 (bs, H 1, H-1II), 4.25±4.19 (m, 1 H,
H-5I), 4.15±4.10 (m, 2 H, H-2II,6Ia), 3.94±3.87 (m,
2 H, H-4II,6IIa), 3.78 (bd, 1 H, J6a,6b ꢀ11 Hz, H-
6IIb), 3.67 (dd, 1 H, J5,6b 4.5, J6a,6b 12.2 Hz, H-6Ib),
3.56 (dd, 1 H, J2,3 3.8, J3,4 9.8 Hz, H-3II), 3.41 (s, 3
H, OCH3); 13C NMR (CDCl3 +D2O): ꢂ 101.10 (C-
1II, JC,H 158.3 Hz), 96.98 (C-1I, JC,H 175.9 Hz),
76.17 (C-5II), 73.81 (C-3II), 71.98 (C-2I), 70.71 (C-
2II), 70.53 (C-3I), 69.10 (C-4I), 68.88 (C-5I), 67.69
(C-6I), 66.19 (C-4II), 60.95 (C-6II), 55.70 (OCH3);
CIMS: m/z 686 ([M+18]+). Anal. Calcd for
C34H36O14: C, 61.07; H, 5.42. Found: C, 60.89; H,
5.51.
(a) A mixture of d-mannose (2, 0.253 g,
1.4 mmol) and dibutyltin oxide (3, 0.312 g,
1.25 mmol) in anhyd methanol (10 mL) was stirred
at 60 ꢁC until a clear solution was obtained
(ꢀ50 min). Toluene (2 mL) was added, and the
mixture was concentrated. The residue, after hav-
(b) A mixture of d-mannose (1, 0.253 g,
1.4 mmol) and dibutyltin oxide (3, 0.312 g,
ꢁ
ing been kept at 50 C/0.2 kPa for 2.5 h, was dis-

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
71
1.27 mmol) in anhyd methanol (15 mL) was stirred
at 60 ꢁC until a clear solution was obtained
give 27 (7.13 g, 94%): [ꢁ]d+3.0ꢁ. Lit [22].
[ꢁ]d+2.8ꢁ.
(ꢀ70 min).
Toluene
(2 mL)
and
tetra-
Attempted anomeric benzylation of d-mannose
via the 1,2-stannylene acetal.ÐA mixture of d-
mannose (2, 2 g, 11.1 mmol) and dibutyltin oxide
(3, 2.76 g, 11.1 mmol) in anhyd methanol (70 mL)
butylammonium ¯uoride monohydrate (0.125 g,
0.47 mmol) was added, and the mixture was con-
centrated. The residue, after having been kept at
ꢁ
ꢁ
50 C/0.2 kPa for 2.5 h, was dissolved in anhyd
was stirred at 60 C until a clear solution was
obtained (ꢀ3 h). Toluene (10 mL) was added, and
acetonitrile (3.0 mL), and molecular sieves (4 A,
0.2 g) were added. After addition of 7 (0.3 g,
0.47 mmol), the mixture was stirred vigorously at
the mixture was concentrated. The residue after
ꢁ
having been kept at 50 C/0.2 kPa for 2.5 h, was
ꢁ
20 C for 24 h, and concentrated. The resulting
dissolved in anhyd N,N-dimethylacetamide
(15 mL), molecular sieves (4 A, 1.0 g) were added,
and after addition of benzyl bromide (2.64 mL,
22.2 mmol) the mixture was stirred vigorously at
suspension was ®ltered through a pad of Celite, the
solids were washed with acetonitrile, and the com-
bined ®ltrate was concentrated. Chromatography
(CH2Cl2±MeOH) gave ®rst 20 (0.055 g, 17.5%).
Eluted second was 12 (0.18 g, 57.3%).
ꢁ
25 C for 24 h and concentrated. The residue was
chromatographed (dichloromethane±methanol) to
give ®rst benzyl 3-O-benzyl-ꢀ-d-mannopyranoside
(25, 0.595 g, 14.9%): mp 112±113 ꢁC (from EtOH),
Methyl 3-O-benzyl-a-d-mannopyranoside (23).
ÐA mixture of methyl ꢁ-d-mannopyranoside (22,
10.0 g, 51.5 mmol) and dibutyltin oxide (3, 12.82 g,
51.5 mmol) in anhyd methanol (100 mL) was stir-
red under re¯ux for 3.5 h, at the end of which time
a clear solution was obtained. Toluene (10 mL) and
cesium ¯uoride (15.64 g, 103.0 mmol) were added,
and the mixture was concenꢁtrated. The residue,
after having been kept at 50 C/0.2 kPa for 2.5 h,
was dissolved in anhyd DMF (70 mL), and mole-
cular sieves (4 A, 5 g) were added. After addition of
benzyl bromide (12.24 mL, 103.0 mmol), the mix-
ture was stirred at room temperature for 20 h, and
concentrated. The residue was triturated with
methanol, and the solids were ®ltered o€. After
addition of water to the ®ltrate, the mixture was
[ꢁ]d 155ꢁ. H NMR (CDCl3): ꢂ 4.88±4.52 (4 d, 1
1
H each, 2 CH2Ph), 4.36 (s, 1 H, H-1), 4.02 (t, 1 H,
J 9.6 Hz, H-4), 3.96 (bd, 1 H, H-2), 3.90 (dd, par-
tially overlapped, J5,6a 3.2, J6a,6b 12.1 Hz, H-6a),
3.81 (dd, partially overlapped, J5,6b 2.7 Hz, H-6b),
3.27 (dd, 1 H, J2,3 3.0, J3,4 9.3 Hz, H-6b), 3.15 (m, 1
H, H-5); 13C NMR (CDCl3): ꢂ 98.41 (C-1, JC,H
158 Hz), 80.83 C-3), 75.96 (C-5), 71.28, 70.51 (2
CH2Ph), 68.01 (C-2), 65.48 (C-4), 61.33 (C-6);
CIMS: m/z 378. Anal. Calcd for C22H24O64: C,
66.65; H, 6.71. Found: C, 66.48; H, 6.73.
Second was eluted a 1:1.2 mixture (1.2 g, 40.0%,
NMR) of benzyl ꢀ-d-mannopyranoside (26) and 3-
O-benzyl-d-mannose (27).
ꢁ
kept overnight at 0 C, the solids were ®ltered o€
Methyl b-d-mannopyranosyl-(1!4)-2,3,6-tri-O-
benzoyl-a-d-glucopyranoside (15).Ð(a) A mixture
of d-mannose (2, 0.181 g, 1.01 mmol) and dibu-
tyltin oxide (3, 0.234 g, 0.94 mmol) in anhyd
and washed with methanol, the combined ®ltrate
was concentrated, and the residue was chromato-
graphed (CH2Cl2±MeOH), to give amorphous 23
(11 g, 72.6%): [ꢁ]d+35.2ꢁ (c 1, EtOH). Lit [21].,
[ꢁ]d+36ꢁ (c 1.2, EtOH). The NMR data agreed
with those reported [21].
ꢁ
methanol (7 mL) was stirred at 60 C until a clear
solution was obtained (1 h). Toluene (2 mL) was
added, and the mixture was concentrated. The
residue, after having been kept at 50 ꢁC/0.2 kPa for
2.5 h, was dissolved in anhyd DMF (1.0 mL),
molecular sieves (4 A, 0.1 g) were added, and, after
addition of methyl 2,3,6-tri-O-benzoyl-4-O-tri-
¯uromethanesulfonyl-ꢁ-d-galactopyranoside [18]
(9, 0.1 g, 0.157ꢁmmol), the mixture was stirred vig-
orously at 25 C for 5 days. After concentration,
the residue was triturated with acetonitrile, the
resulting suspension was ®ltered through a pad of
Celite, solids were washed with acetonitrile, and
the combined ®ltrate was concentrated. Chroma-
tography (CH2Cl2±MeOH) gave 15 (0.04 g,
40.0%): mp 106±107 ꢁC (from ethanol); [ꢁ]d
3-O-Benzyl-1,2,4,6-tetra-O-acetyl-a-d-mannopy-
ranose (24).ÐA solution of 23 (4.0 g) in 50:20:0.5
(v/v) Ac2O±AcOH±H2SO4 (35 mL) was stirred at
ꢁ
20 C for 4 h. The reaction mixture was poured
into ice-water (30 mL), and, when the excess of
Ac2O was hydrolyzed, it was partitioned between
dichloromethane and aq NaHCO3. The organic
layer was dried, concentrated, and chromato-
graphy (hexane±ethyl acetate) gave amorphous 24
(5.3 g, 89.0%): [ꢁ]d+0.20ꢁ. Lit [22]. [ꢁ]d+0.28ꢁ.
The NMR data agreed with those reported [21].
3-O-Benzyl-a-d-mannopyranose (27).ÐCom-
pound 24 (12.3 g) was deacetylated (Zemplen) to

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
72
+104ꢁ. H NMR (CDCl3+D2O): ꢂ 6.00 (t, 1 H, J
9.6 Hz, H-3I), 5.23 (dd, 1 H, J1,2 3.6, J2,310.2 Hz, H-
2I), 5.13 (d, 1 H, H-1I), 4.70 (bd, 1 H, H-6Ia), 4.61
(dd, 1 H, J5,6a 4.2, J5,6b 12.3 Hz, H-6Ib), 4.58 (s, 1 H,
H-1II), 4.28 (m, 1 H, H-5I), 4.12 (t, 1 H, J 9.4 Hz, H-
4I), 3.95 (d, 1 H, J2,3 2.5 Hz, H-2II), 3.56 (t, 1 H, J
9.4, H-4II), 3.41 (s, 3 H, OCH3), 3.34 (dd, 1 H, J3,4
9.4 Hz, H-3II), 3.17 (dd, 1 H, J5,6a 3.5, J6a,6b 12.3 Hz,
H-6IIa), 3.04 (dd, 1 H, J5,6b 2.4 Hz, H-6IIb), 2.83
(dbt, 1 H, H-5II); 13C NMR (CDCl3): ꢂ 100.55 (C-
1II, JC,H 156.3 Hz), 96.79 (C-1I, JC,H 176.1 Hz), 76.87
(C-4I), 76.04 (C-5II), 73.55 (C-3II), 71.80 (C-2I), 71.17
(C-3I), 70.89 (C-2II), 68.38 (C-5I), 65.79 (C-4II),
63.08 (C-6I), 60.51 (C-6II), 55.40 (OCH3); CIMS: m/
mixture of 3-O-benzyl-d-mannose (25) (0.618 g,
2.28 mmol) and dibutyltin oxide (3, 0.546 g,
2.197 mmoꢁl) in anhyd methanol (25 mL) was stir-
red at 70 C until a clear solution was obtained
(65 min). Toluene (4 mL) and tetrabutylammonium
¯uoride monohydrate (0.115 g, 0.439) were added,
and the mixture was concenꢁtrated. The residue,
after having been kept at 50 C/0.2 kPa for 2.5 h,
was dissolved in anhyd acetonitrile (3.5 mL), and
molecular sieves (4 A, 0.2 g) were added. After
addition of 7 (0.3 g, 0.439 mmol), the mixture was
stirred vigorously at 20 ꢁC for 20 h and con-
centrated. The residue was processed as described
above, and chromatography (CH2Cl2±MeOH)
1
z 686 ([M+18]+). Anal. Calcd for C34H36O14 0.5
gave 14 (0.26 g, 72.6%): [ꢁ]d +16.2ꢁ; H NMR
1
.
H2O: C, 60.26; H, 5.50. Found: C, 60.41; H, 5.52.
(b)
(CDCl3+D2O): ꢂ 6.15 (t, 1 H, J 9.7, H-3I), 5.63 (t,
1 H, J 9.7, H-4I), 5.27 (dd, 1 H, J1,2 3.1, J2,3 10.1,
H-2I), 5.22 (d, 1 H, H-1I), 4.78, 4.63 (2 d, 1 H each,
2J 12.3 Hz, CH2Ph), 4.41 (s, 1 H, H-12), 4.27±4.20
(m, 1 H, H-5I), 4.19 (d, 1 H, J2,3 3.1, H-2II), 4.14
(dd, 1 H, J5,6a 2.0, J6a,6b 11.5 Hz, H-6Ia), 4.02 (t, 1
H, J 9.5 Hz, H-4II), 3.83 (dd, partially overlapped,
J5,6a 4.1, J6a,6b 11.8 Hz, H-6IIa), 3.78 (dd, partially
overlapped, J5,6b 3.3 Hz, H-6IIb), 3.68 (dd, 1 H,
J5,6b 6.4 Hz, H-6Ib), 3.41 (s, 3 H, OCH3), 3.36 (dd,
1 H, H-3II); 13C NMR (CDCl3+D2O): ꢂ 100.86
(C-1II, JC,H 158.6 Hz), 96.93 (C-1I, JC,H 175.7 Hz),
80.57 (C-3II), 75.88 (C-5II), 71.96 (C-2I), 71.09
(CH2Ph), 70.41 (C-3I), 69.18 (C-4I), 68.76 (C-2II),
67.91 (C-6I), 67.51 (C-5I), 65.80 (C-4II), 58.64 (C-
6II), 55.60 (OCH3); CIMS: m/z 776 ([M+18]+).
Anal. Calcd for C41H42O14: C, 64.90; H, 5.58.
Found: C, 64.85; H, 5.59.
A
mixture of d-mannose (2, 0.36 g,
2.00 mmol) and dibutyltin oxide (3, 0.47 g,
1.88 mmol) in anhyd methanol (13 mL) was stirred
at 60 ꢁC until a clear solution was obtained
(ꢀ1.5 h). Toluene (2 mL) was added, and the
mixture was concentrated. The residue, after hav-
ꢁ
ing been kept at 50 C/0.2 kPa for 2.5 h, was dis-
solved in anhyd DMA (1.5 mL), molecular sieves
(4 A, 0.2 g) and diisopropylethylamine (0.14 mL,
0.94 mmol) were added, and, after addition of
methyl 2,3,6-tri-O-4-O-tri¯uromethanesulfonyl-ꢁ-
d-galactopyranoside [18] (9, 0.2 g, 0.35 mmol), the
ꢁ
mixture was stirred vigorously at 25 C for 3 days
and concentrated. The residue was triturated with
acetonitrile, the resulting suspension was ®ltered
through a pad of Celite, solids were washed with
acetonitrile, and the combined ®ltrate was con-
centrated. Chromatography (CH2Cl2±MeOH) gave
15 (0.11 g, 52.6%).
Methyl 3-O-benzyl-b-d-mannopyranosyl-(1!4)-
2,3,6-tri-O-benzoyl-a-d-glucopyranoside (16).ÐA
mixture of 3-O-benzyl-d-mannose (25) (0.552 g,
2.03 mmol) and dibutyltin oxide (3, 0.468 g,
1.88 mmol) in anhyd MeOH (25 mL) was stirred at
70 ꢁC until a clear solution was obtained
(ꢀ60 min). Toluene (4 mL) and CsF (0.285 g,
1.88 mmol) were added, and the mixture was con-
centrated. The residue, after having been kept at
50 ꢁC/0.2 kPa for 2.5 h, was dissolved in anhydrous
DMF (1.5 mL), and molecular sieves (4 A, 0.2 g)
were added. After addition of 9 [18] (0.2 g,
0.313 mmol), the mixture was ꢁstirred vigorously at
(c)
A
mixture of d-mannose (2, 0.36 g,
2.00 mmol) and dibutyltin oxide (3, 0.47 g,
1.88 mmol) in anhyd methanol (13 mL) was stirred
at 60 ꢁC until a clear solution was obtained (1.6 h).
CsF (0.29 g, 1.88 mmol) and toluene (2 mL) was
added, and the mixture was concentrated. The
ꢁ
residue, after having been kept at 50 C/0.267 kPa
for 2.5 h, was dissolved in anhyd Me2SO (1.5 mL),
molecular sieves (4 A, 0.2 g) were added and, after
addition of methyl 2,3,6-tri-O-benzyl-4-O-tri-
¯uromethanesulfonyl-ꢁ-d-galactopyranoside [18]
(9, 0.2 g, 0.35ꢁmmol), the mixture was stirred vig-
orously at 25 C for 2 days and concentrated. The
residue was treated as described above, and chro-
matography gave 15 (0.12 g, 59.0%).
ꢁ
( 5)±0 C for 4 h, and at 20 C for another 16 h.
After concentration, the residue was processed as
described above, and chromatography (CH2Cl2±
MeOH) gave 16 (0.16 g, 67.5%): [ꢁ]d +83ꢁ. H
1
Methyl 3-O-benzyl-b-d-mannopyranosyl-(1!6)-
NMR (CDCl3+D2O): ꢂ 5.96 (dd, 1 H, J2,3 10.3,
J3,4 8.6 Hz, H-3I), 5.33 (dd, 1 H, J1,2 3.7, H-2I),
2,3,6-tri-O-benzoyl-a-d-glucopyranoside (14).ÐA

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G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
73
5.12 (d, 1 H, H-1I), 4.70, 4.48 (2 d, partially over-
lapped, 2J 11.9 Hz, CH2Ph), 4.67 (dd, partially
overlapped, J5,6a 2.0, J6a,6b 12.1 Hz, H-6Ia) 4.57
(dd, 1 H, J5,6b 3.9, H-6b), 4.49 (s, overlapped, H-
1II), 4.29±4.22 (m, 1 H, H-5I), 4.18 (t, 1 H, J 8.6, H-
4I), 4.04 (d, 1 H, J2,3 2.9 Hz, H-2II), 3.63 (t, 1 H, J
9.4, H-4II), 3.45 (s, 3 H, OCH3), 3.22±3.14 (m, 2 H,
H-3II,6IIa), 2.95±2.87 (m, 2 H, H-5II,6IIb); 13C
chromatography gave the amorphous methyl 2,4,6-
tri-O-benzoyl-ꢀ-d-mannopyranosyl-(1!4)-2,3,6-
tri-O-benzoyl-ꢁ-d-glucopyranoside (18) (0.075 g,
82.4%): [ꢁ]d +15.6ꢁ. 1H NMR (CDCl3): ꢂ 5.99 (m,
1 H, H-3I), 5.70 (bd, 1 H, J2,3 ꢀ3 Hz, H-2II), 5.32 (t,
J 9.8 Hz, H-4II), 5.18±5.12 (m, 2 H, H-1I,2I), 4.91 (s,
1 H, H-1II), 4.67 (m, 2 H, H-6Ia,b), 4.25±4.17 (m, 3
H, H-4I,5I,6IIa), 4.10±3.95 (m, 2 H, H-3II,6IIb), 3.72
(ddd, J5,6a 2.8, J5,6b 4.9, J6a,6b 9.6 Hz, H-5II), 3.38 (s,
3 H, OCH3), 2.65 (d, 1 H, J3,OH 7.1 Hz, OH); 13C
NMR (CDCl3): ꢂ 98.38 (C-1II), 96.86 (C-1I), 75.87
(C-4I), 72.37 (C-5II), 72.10 (C-2I), 71.80 (C-2II),
71.62 (C-3II), 70.20 (C-4II), 69.80 (C-3I), 68.34 (C-
5I), 62.86 (2 C, C-6I,II), 55.45 (OCH3); CIMS: m/z
998 ([M+18]+).
NMR (CDCl3+D2O):
ꢂ
99.29 (C-1II, JC,H
157.7 Hz), 96.99 (C-1I, JC,H 171 Hz), 80.84 (C-3II),
75.79 (C-5II), 75.34 (C-4I), 71.18 (2 C, C-2I,3I),
71.02 (CH2Ph), 68.34 (C-5I), 67.41 (C-2II), 66.00
(C-4II), 62.98 (C-6I), 61.66 (C-6II), 55.51 (OCH3);
CIMS: m/z 776 ([M+18]+). Anal. Calcd for
C41H42O14: C, 64.90; H, 5.58. Found: C, 64.71; H,
5.64.
.
BF3 Et2O (0.029 mL, 0.23 mmol) was added at
0±+5 C to a stirred solution of lactosyl imidate
ꢁ
Methyl 2,4,6-tri-O-benzoyl-3-O-benzyl-b-d-man-
nopyranosyl-(1!4)-2,3,6-tri-O-benzoyl-a-d-glucopy-
[20] 28 (0.183 g, 0.245 mmol) and 18 (0.140 g,
0.143 mmol) in anhyd CH2Cl2 (1 mL). The mixture
was allowed to reach slowly at 20 ꢁC within ꢀ3.5 h,
when the reaction mixture was neutralized by
addition of triethylamine. After concentration,
chromatography (hexane±EtOAc) gave 29 (0.16 g,
70%): [ꢁ]d 9ꢁ. 1H NMR (CDCl3): ꢂ 3.96 (m, 1 H,
H-3I), 5.79 (bd, 1 H, J2,3 ꢀ3 Hz, H-2II), 5.41 (t, 1
H, J 9.9 Hz, H-4II), 5.27 (bd, 1 H, J3,4 ꢀ2.9 Hz, J4,5
<1 Hz), 5.16±5.10 (m, 2 H, H-1I,2I), 5.09±5.00 (m,
2 H, H-2IV,3III), 4.85 (dd, partially overlapped, J3,4
3.4, J2,3 10.2 Hz, H-3IV), 4.83 (s, partially over-
lapped, H-1II), 4.74 (dd, 1 H, J5,6a 3.2, J6a,6b
12.2 Hz, H-6Ia), 4.66±4.60 (m, 3 H, H-1III,2III,6Ib),
4.25±4.13 (m, 6 H, H-1IV,3II,4I,5I,6IIa,6IIIa), 4.03±
3.95 (m, 2 H, H-6IVa,b), 3.91 (dd, partially over-
lapped, J5,6b 5.6, J6a,6b 12.0 Hz, H-6IIb), 3.85 (dd,
partially overlapped, J5,6b 4.1, J6a,6b 11.5 Hz, H-
6IIIb), 3.74±3.66 (m, 2 H, H-5II,IV), 3.64±3.54 (m, 2
H, H-4III,5III); 13C NMR (CDCl3): ꢂ 100.96 (C-1IV,
JC,H 161.2 Hz), 98.30 (C-1II, JC,H 155.1 Hz), 97.24
(C-1III, JC,H 164.8 Hz), 96.86 (C-1I, JC,H 175 Hz),
75.96 (C-4III), 75.75 (C-4I), 75.21 (C-3II), 72.99 (C-
3III), 72.37 (2 C, C-5II,5III), 72.01 (C-2I), 71.17 (C-
2III), 70.85 (C-3IV), 70.53 (C-5IV), 69.68 (C-3I),
68.94 (C-2IV), 68.21 (C-5I), 67.77 (C-2II), 67.63 (C-
4II), 66.49 (C-4IV), 63.03 (C-6I,6II), 62.14 (C-6III),
60.66 (C-6IV), 54.47 (OCH3); CIMS: m/z 1618
([M+18]+). Anal. Calcd for C81H82O34: C, 60.82;
H, 5.17. Found: C, 60.76; H, 5.23.
ranoside
(17).ÐBenzoyl
chloride
(0.25 mL,
ꢁ
2.3 mmol) was slowly added at 20 C to a stirred
solution of 16 (0.5 g, 0.66 mmol) in anhyd pyridine
(5 mL). After 4 h the reaction was quenched by
addition of methanol, the mixture was con-
centrated, and chromatography (toluene±EtOAc)
ꢁ
gave 17 (0.6 g, 85%): mp. 101±102 C (from etha-
nol); [ꢁ]d 11.5ꢁ, 1H NMR (CDCl3): ꢂ 6.01 (t, 1 H,
J 9.0 Hz, H-3I), 5.92 (bd, 1 H, H-2II), 5.50 (t, 1 H, J
9.8 Hz, H-4II), 5.16 (dd, partially overlapped, J2,3
10.3 Hz, H-2I), 5.12 (d, partially overlapped, H-1I),
4.82 (bs, 1 H, H-1II), 4.76 (dd, 1 H, J5,6a 3.4, J6a,6b
2
12.7 Hz, H-6Ia), 4.65 (d, partially overlapped, J
12.7 Hz, CHaPh), 4. 63 (dd, partially overlapped,
J5,6b 2.0 Hz, H-6Ib), 4.45 (d, 1 H, CHb Ph), 4.29±
4.19 (m, 2 H, H-5I, incl t at 4.22, J 8.5, H-4I), 4.14
(dd, 1 H, J5,6a 3.6, J6a,6b 12.6 Hz, H-6IIa), 3.94 (dd,
1 H, J5,6b 5.1 Hz, H-6IIb), 3.72 (dd, 1 H, J2,3 3.1, H-
3II), 3.61 (ddd, 1 H, H-5II), 3.38 (s, 3 H, OCH3);
13C NMR (CDCl3): ꢂ 98.57 (C-1II), 96.86 (C-1I),
75.95 (2 C, C-4I,3II), 72.50 (C-5II), 72.06 (C-2I),
70.45 (CH2Ph), 69.76 (C-3I), 68.31 (C-5I), 68.01 (C-
4II), 67.70 (C-2II), 62.94 (C-6II), 62.91 (C-6I), 55.42
(OCH3); CIMS: m/z 1089 ([M+18]+. Anal. Calcd
for C62H54O17: C, 69.52; H, 5.08. Found: C, 69.46;
H, 5.13.
Methyl (2,3,4,6-tetra-O-acetyl-b-d-galactopyran-
osyl)-(1!4)-2,3,6-tri-O-acetyl-b-d-glucopyranosyl)-
(1!3)-2,4,6-tri-O-benzoyl-b-d-mannopyranosyl-
(1!4)-2,3,6-tri-O-benzoyl-a-d-glucopyranoside (29). Ð
A solution of the 3-O-benzyl derivative 17 (0.1 g) in
ethanol (5 mL) was stirred under hydrogen at 50 ꢁC
until TLC (solvent) showed that the reaction was
complete (ꢀ48 h). Conventional processing and
Methyl 2,3,4,6-tetra-O-acetyl-a-d-glucopyranosyl-
(1!4)-1,3,6-di-O-acetyl-2-O-(methyl 2,3,6-tri-O-
benzoyl-a-d-glucopyranos-2-yl)-b-d-glucopyrano-
side (methyl 2,3,6-tri-O-benzoyl-4-O-(hepta-O-
acetyl-b-maltos-2-yl)-a-d-glucopyranoside (32).ÐA

Â
G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
74
mixture of maltose (30, 1.044 g, 2.9 mmol) and
dibutyltin oxide (3, 0.649 g, 2.6 mmol) in anhyd
methanol (30 mL) was stirred at 70 ꢁC until a clear
solution was obtained (ꢀ1 h). Toluene (2 mL) and
acetonitrile (4 mL). After addition of 7 (0.1 g,
0.16 mmol), the mixture was stirred vigorously at
50 C for 10 h, and concentrated. The residue was
ꢁ
separated by column chromatography (toluene±
ethyl acetate containing a little triethylamine) to
give ®rst a small amount of a byproduct, methyl
4,6-O-benzylidene-ꢀ-d-glucopyranos-2-yl-(2!6)-
2,3,4-tri-O-benzoyl-ꢁ-d-glucopyranoside (34):
CIMS: m/z 775 ([M+18]+). The material was
acetylated as described for the preparation of 32,
to give methyl 1,3-di-O-acetyl-4,6-O-benzylidene-
ꢁ,ꢀ-d-glucopyranos-2-yl-(2!6)-2,3,4-tri-O-benzoyl-
tetrabutylammonium
¯uoride
monohydrate
(0.605 g, 2.316 mmol) was added, and the mixture
was concentrated. The residue, after having been
ꢁ
kept at 50 C/0.2 kPa for 2.5 h, was dissolved in
anhyd DMF (3.5 mL). After addition of 9 (0.27 g,
0.429 mmol), the mixture was stirred vigorously at
ꢁ
20 C for 20 h, and concentrated. The residue was
chromatographed (CH2Cl2±MeOH), to give 31
(0.261 g, 74.6%) as a mixture of anomers, CIMS:
m/z 846 ([M+18]+).
1
ꢁ-d-glucopyranoside (36). H NMR for the pre-
dominating ꢀ-anomer (CDCl3): ꢂ 6.13 (t, 1 H, J
9.6 Hz, H-3I), 5.74 (d, 1 H, J1,2 7.6 Hz, H-1II), 5.45
(s, partially overlapped, CHPh), 5.44 (t, partially
overlapped, H-4I), 5.34 (t, 1 H, J 9.2, H-3II), 5.21
(dd, 1 H, J1,2 3.6, J2,3 10.0 Hz, H-2I), 5.16 (d, 1 H,
H-1I), 4.36 (dd, 1 H, J5,6 5.6, J6a,6b 9.6 Hz, H-6IIa),
4.14 (m, 1 H, H-5I), 3.87 (dd, 1 H, J5,6a 6.4, J6a,6b
10.4 Hz, H-6Ia), 3.76 (dd, partially overlapped,
J5,6b 1.6 Hz, H-6Ib), 3.70 (d, partially overlapped,
H-6IIb), 3.68±3.56 (m, 2 H, H-4II,5II), 3.49 (dd,
partially overlapped, H-2II), 3.43 (s, 3 H, OCH3),
Acetic anhydride (1 mL) was added slowly, with
ꢁ
stirring, at 100 C, to a solution of the foregoing
material in pyridine (2 mL). After usual processing,
chromatography (toluene±EtOAc) gave 32: [ꢁ]d
+115ꢁ. H NMR (CDCl3) for the ꢀ-anomer (lar-
1
gely predominating): ꢂ 5.81 (bt, 1 H, J 10.1 Hz, H-
3I), 5.61 (d, 1 H, J1,2 7.5 Hz, H-1II), 5.24 (t, par-
tially overlapped, H-3III), 5.19 (t, partially over-
lapped, J 9.0 Hz, H-3II), 5.11±5.05 (m, 2 H, H-
1I,2I), 5.02 (t, partially overlapped, J 9.7 Hz, H-
4III), 4.96 (d, partially overlapped, J1,2 ꢀ4 Hz, H-
1III), 4.80 (dd, 1 H, J1,2 4.0, J2,310.5 Hz, H-2III),
4.47 (m, 2 H, H-6Ia,b), 4.31 (dd, 1 H, J5,6a 2.0, J5,6b
11.8 Hz, H-6IIa), 4.24±4.08 (m, 4 H, H-4I,5I,6II-
b,6IIIa), 4.00±3.90 (m, 2 H, H-2II,6IIIb), 3.80 (m, 1
H, H-5III), 3.72 (m, 1 H, H-5II), 3.42 (s, 3 H,
OCH3), 3.33 (t, 1 H, J 9.0 Hz, H-4II), 2.24, 2.09,
2.08, 2.06, 2.00, 1.97, 1.94 (7 s, 3 H each, 7
COCH3); 13C NMR (CDCl3): ꢂ 96.57 (C-1I), 95.42
(C-1III), 93.88 (C-1II), 76.87 (C-2II), 75.32 (C-4I),
73.93 (C-3I), 73.85 (C-3II), 73.03 (C-5II), 72.93 (C-
4II), 72.30 (C-2I), 69.71 (C-2III), 69.37 (C-3III),
68.34 (C-5III), 68.00 (C-5I), 67.93 (C-4III), 63.65 (C-
6I), 62.53 (C-6II), 61.46 (C-6III), 55.33 (OCH3);
CIMS: m/z 1142 ([M+18]+). Anal. Calcd for
C54H60O26: C, 57.65; H, 5.38. Found: C, 57.56 ; H,
5.39.
2.09, 1.95 (2 s, 3 H, each, 2 COCH3) ; ꢂH-1 6.40,
ꢁ
J1,2 3.3 Hz; 13C NMR (CDCl3): ꢂ 101.44 (CHPh),
96.75 (C-1I), 93.78 (C-1II), 80.19 (C-2II), 78.37 (C-
4II), 72.64 (C-3II), 72.09 (C-2I), 70.35 (C-3I), 69.35
(C-4I), 69.12 (C-5I), 68.42 (2 C, C-6I,II), 66.74 (C-
5II), 55.53 (OCH3); CIMS: m/z 858 ([M+18]+).
Second eluted was the title compound 35
(0.068 g, 57.1%): [ꢁ]d +15.6ꢁ. 1H NMR
(CDCl3+D2O): ꢂ 6.19 (m, 1 H, H-3I), 5.87 (t, 1 H,
J 9.8 Hz, H-4I), 5.54 (s, 1 H, CHPh), 5.32±5.28 (m,
2 H, H-1I,2I), 4.35 (d, partially overlapped, J1,2
7.5 Hz, H-1II), 4.32 (dd, partially overlapped, J5,6a
5.0 Hz, H-6IIa), 4.27±4.19 (m, 2 H, H-5I,6Ia), 3.87±
3.80 (m, 2 H, H-3II,6IIb), 3.72±3.61 (m, 3 H, H-
2II,6Ib, incl t at 3.64, J 10.0 Hz, H-4II), 3.47 (s par-
tially overlapped, OCH3), 3.49±3.40 (m, partially
overlapped, H-5II); 13C NMR (CDCl3+D2O): ꢂ
103.53 (C-1II, JC,H 159.6 Hz), 101.84 (CHPh),
97.30 (C-1I, JC-1,H-1 175.7 Hz), 80.17 (C-4II), 74.43
(C-2II), 72.91 (C-3II), 72.94 (C-2I), 70.36 (C-3I),
68.74 (C-4I), 68.55 (C-6II), 68.08 (C-5I), 67.83 (C-
6I), 66.59 (C-5II), 55.79 (OCH3); CIMS: m/z 775,
([M+18]+).
Methyl
4,6-O-benzylidene-b-d-glucopyranosyl-
(1!6)-2,3,4-tri-O-benzoyl-a-d-glucopyranoside
(35).ÐA mixture of 4,6-O-benzylidene-d-glucose
(33, 0.252 g, 0.94 mmol) and dibutyltin oxide (3,
0.230 g, 0.94 mmol) in anhyd methanol (10 mL)
ꢁ
was stirred at 60 C until a clear solution was
obtained (ꢀ1 h). Toluene (2 mL) and tetra-
butylammonium ¯uoride monohydrate (0.047 g,
0.16 mmol) was added, and the mixture was con-
centrated. The residue, after having been kept at
50 ꢁC/0.2 kPa for 2.5 h, was dissolved in anhydrous
For characterization, a portion was acetylated
with 1:1 pyridine±acetic anhydride to give methyl
2,3-di-O-acetyl-4,6-O-benzylidene-ꢀ-d-glucopyr-
anosyl-(1!6)-2,3,4-tri-O-benzoyl-ꢁ-d-glucopyr-
ꢁ
1
anoside (37) as a foam: [ꢁ]d +1.7 (c 0.9). H

Â
G. Hodosi, P. KovacÆ/Carbohydrate Research 308 (1998) 63±75
75
NMR (CDCl3): ꢂ 6.18±6.10 (m, H-3I), 5.47 (t, s, 2
H, partially overlapped, Jꢀ10.8 Hz, H-4I, CHPh),
5.33 (t, J 9.5 Hz, H-3II), 5.28±5.22 (m, 2 H, H-
1I,2I), 5.06 (dd, 1 H, J1,2 7.8, J2,3 9.2 Hz, H-2II),
4.66 (d, 1 H, J1,2 7.8 Hz, H-1II), 4.32 (dd, 1 H, J5,6a
5.1, J6a,6b 10.5 Hz, H-6IIa), 4.23 (ddd, 1 H, J5,6a 1.7,
J5,6b 6.1, J4,5 9.8 Hz, H-5I), 4.06 (dd, 1 H, J6a,6b
10.8 Hz, H-6Ia), 3.78±3.64 (m, 3 H, H-6Ib,6IIb, incl
t, partially overlapped, J 9.5 Hz, H-4II), 3.57±3.45
(m, 4 H, H-5II, incl s, 3.45, OCH3), 2.11, 2.05 (2 s,
3 H each, 2 COCH3); 13C NMR (CDCl3): ꢂ 101.40
(2 C, C-1II, CHPh), 96.76 (C-1I), 78.20 (C-4I),
72.03 (C-2II), 71.94 (C-2I), 71.65 (C-3II), 70.40 (C-
3I), 69.19 (C-4I), 68.50 (C-5I), 68.39, 68.34 (C-6I,II),
66.28 (C-5II), 20.76, 20.71 (2 COCH3); CIMS: m/z
858 ([M+18]+). Anal. Calcd for C45H44O16: C,
64.28; H, 5.27. Found: C, 64.23; H, 5.35.
Synthesis, Vol. 1, pp 251±276, Harwood Academic,
Amsterdam, 1996.
[7] G. Hodosi and P. Kovac, J. Am. Chem. Soc., 119
(1997) 2335±2336.
[8] R.R. Schmidt, M. Reichrath, and U. Moering,
Chem. Ber., 115 (1982) 39±49.
[9] R.R. Schmidt, in B.M. Trost (Ed.), Comprehensive
Organic Synthesis, Vol. 6, pp 33±64, Pergamon
Press, 1991.
[10] R.R. Schmidt, Angew. Chem. Int. Ed. Engl., 25
(1986) 212±235.
[11] G. Hodosi and P. Hovac, Carbohydr. Res., 300
(1997) 239±243.
[12] V.K. Srivastava and C. Schuerch, Tetrahedron
Lett., (1979) 3269±3272.
[13] A. Dessinges, A. Olesker, G. Lukacs, and T.T.
Thang, Carbohydr. Res., 126 (1984) C6±C8.
[14] G. Hodosi and P. Kovac, J. Carbohydr. Chem., in
press.
[15] G. Hodosi, unpublished results.
[16] P. Kovac, V. Sklenar, and C.P.J. Glaudemans,
Carbohydr. Res., 175 (1988) 201±213.
[17] M.G. Ambrose and R.W. Binkley, J. Org. Chem.,
48 (1982) 674±677.
[18] L.A. Reed and L. Goodman, Carbohydr. Res., 94
(1981) 91±99.
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