A study on the influence of the structure of the glycosyl acceptors on the stereochemistry of the glycosylation reactions with 2-azido-2-deoxy- hexopyranosyl trichloroacetimidates

Article abstract of DOI:10.1002/chem.200400746

The stereochemical outcome of glycosylations with 2-azido-2-deoxy- D-gluco- and D-galactopyranosyl trichloroacetimidates as glycosyl donors has been investigated by using a series of chiro-inositol derivatives as glycosyl acceptors. The influence of the absolute configuration, the conformation and the conformational flexibility of the glycosyl acceptor has been studied by using different glycosyl donors under similar pre-established experimental conditions. Although the structure of the acceptor may play a role in governing the stereochemistry of these glycosylations, the results show that, in general terms, the relative influence of these factors is difficult to evaluate. For a given set of experimental conditions, the stereochemical course of these glycosylations depends on structural features of both glycosyl donor and glycosyl acceptor. It is a balance of these factors, where the structure of the glycosyl donor always plays a major role, which determines the stereochemistry of the coupling reaction. Therefore, the examples reported in the literature in which the structure of the glycosyl acceptor appears to be crucial in determining the stereochemistry of the reaction constitute particularly favorable cases which do not presently allow any further generalization.

Full text of DOI:10.1002/chem.200400746

A Study on the Influence of the Structure of the Glycosyl Acceptors on the
Stereochemistry of the Glycosylation Reactions with 2-Azido-2-Deoxy-
Hexopyranosyl Trichloroacetimidates
M. Belꢀn Cid,*[a] Francisco Alfonso,[b] and Manuel Martꢁn-Lomas*[b]
Abstract: The stereochemical outcome
of glycosylations with 2-azido-2-deoxy-
d-gluco- and d-galactopyranosyl tri-
chloroacetimidates as glycosyl donors
has been investigated by using a series
of chiro-inositol derivatives as glycosyl
acceptors. The influence of the abso-
lute configuration, the conformation
and the conformational flexibility of
the glycosyl acceptor has been studied
by using different glycosyl donors
under similar pre-established experi-
mental conditions. Although the struc-
ture of the acceptor may play a role in
governing the stereochemistry of these
glycosylations, the results show that, in
general terms, the relative influence of
these factors is difficult to evaluate.
For a given set of experimental condi-
tions, the stereochemical course of
these glycosylations depends on struc-
tural features of both glycosyl donor
and glycosyl acceptor. It is a balance of
these factors, where the structure of
the glycosyl donor always plays
a
major role, which determines the ster-
eochemistry of the coupling reaction.
Therefore, the examples reported in
the literature in which the structure of
the glycosyl acceptor appears to be cru-
cial in determining the stereochemistry
of the reaction constitute particularly
favorable cases which do not presently
allow any further generalization.
Keywords: carbohydrates
· glyco-
sides · glycosylation · oligosacchar-
ides
Introduction
ipating protecting group in glycosylation reactions, was first
introduced by Paulsen[4] and has been extensively used in
complex oligosaccharide synthesis ever since.[5] The stereo-
chemical outcome of glycosylations by using 2-azido-2-
deoxy sugars as glycosyl donors, however, is not always pre-
dictable and seems to depend on the nature of the anomeric
leaving groups and on that of the promoters used in the gly-
cosylations.[5] Furthermore, by using imidates as glycosyl
donors, the stereochemistry has been reported to be also
strongly dependent on the experimental conditions, the ori-
entation of the leaving group and the nature of the accept-
or.[5,6] Consequently, the stereoselectivity of these glycosyla-
tion reactions is difficult to forecast[6a] particularly when the
trichloroacetimidate method, which is most frequently em-
ployed in the synthesis of complex oligosaccharide mole-
cules, is used.[6b–d]
A considerable number of oligosaccharides of biological sig-
nificance contain a-linked d-glucosaminyl or d-galactosa-
minyl units.[1] Therefore, the stereoselective construction of
these 1,2-cis glycosidic linkages is a matter of current inter-
est in areas of glycobiology where the synthesis of these
complex oligosaccharides is needed.[2] The major require-
ment for the stereoselective synthesis of 1,2-cis glycosidic
bonds is the presence of a non-participating group at C-2 of
the glycosyl donor, and the most commonly used non-partic-
ipating group to install the a-d-glucosaminyl and the a-d-
galactosaminyl linkages is the azido group.[3] The 2-azido
moiety, serving both as a latent function and as a non-partic-
[a] Dr. M. B. Cid
A remarkable example has been reported by Seeberger
et al.[7] In developing a modular synthesis of heparin-like oli-
gosaccharides, these authors have shown that, locking the
Departamento de Quꢀmica Orgꢁnica
Universidad Autꢂnoma de Madrid, 28049 Cantoblanco (Spain)
Fax : (+34)91-497-3966
1
E-mail: belen.cid@uam.es
conformation of a glucuronic acid acceptor in the C4 form
[b] F. Alfonso, Prof. Dr. M. Martꢀn-Lomas
Grupo de Carbohidratos
1, the glycosylation reaction with a conveniently protected
2-azido-2-deoxy-d-glucopyranosyl trichloroacetimidate led
to the completely selective formation of the desired 1,2-cis
disaccharide; the reaction of the same donor with the un-
Instituto de Investigaciones Quꢀmicas, CSIC
Amꢃrico Vespucio s/n, 41092 Sevilla (Spain)
Fax : (+34)95-446-0565
4
E-mail: manuel.martin-lomas@iiq.csic.es
locked acceptor in the C1 conformation 2 gave mixtures of
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FULL PAPER
1,2-cis and 1,2-trans isomers.[7] These results, which have also
been shown to occur when using fluorides as donors, seem
to indicate that the stereochemical outcome of these glyco-
sylations is, in this case, also related to the flexibility and the
conformation of the acceptor. We have found, also in the
field of synthetic heparin fragments, that the glycosylation
of a tightly locked l-iduronic acid lactone 3 gives the corre-
sponding a-glycoside with a good although poorer selectivity
than the glycosylation of the corresponding unlocked l-idur-
onic acid derivative 4 (Figure 1).[8]
and also OH-6 in the d-myo series (see for instance com-
pound 8 frequently used in our laboratory as glycosyl ac-
ceptor) can be described as equatorial-like according to
NMR data. On the other hand, since no significant differen-
ces in the stereoselectivity were observed in the glycosyla-
tion of 5–7, conformational constrain did not appear to play
an important role in this case (Figure 2).
Figure 2. d-myo- and d-chiro-inositol glycosyl acceptors.
Because of our interest in obtaining building blocks for
the synthesis of l-chiro-inositol containing IPGs[11i] we now
have also investigated the stereochemistry of the formation
of the 1!1 glycosidic linkage in the l-chiro-inositol series.
Considering the difficulties found for the construction of
this structural motif in the d series, we thought that a paral-
lel study using the enantiomeric l-chiro-inositol acceptors
would offer a good opportunity to get some additional in-
sight into the influence of steric and conformational features
of the acceptor on the stereoselectivity by comparing the
data from both the d- and the l-chiro series. The results of
this study are presented and discussed below.
Figure 1. Glucuronic and iduronic acid glycosyl acceptors.
There are many cases in the literature showing the stereo-
selective formation of both 1,2-cis and 1,2-trans glycosidic
bonds from donors bearing the 2-azido function, but the
possible influence of the structure of the acceptor on the
stereoselectivity has not been systematically investigated.[5,6]
The intrinsic reactivity of the hydroxyl groups, primarily in
terms of axial or equatorial orientation affecting the reactiv-
ity–selectivity balance[9] and steric factors resulting in match-
ed/mismatched donor–acceptor pairs[10a] could be major
players. However, our present understanding of the possible
role of the acceptor in the stereochemistry of these complex
reactions is still far from satisfactory.
Results and Discussion
As a consequence of our continued interest in the synthe-
sis of inositolphosphoglycan (IPG)-type compounds as po-
tential mediators in the insulin signaling process[11] we have
worked extensively with 2-azido-2-deoxy-d-gluco- and d-gal-
actopyranosyl trichloroacetimidates, as glycosyl donors, and
with a variety of myo- and chiro-inositol derivatives as gly-
cosyl acceptors. The stereoselectivity of these glycosylations
also seemed to be somehow dependent on the structure of
the acceptor. In the case of the d-chiro-inositol derivatives,
where a series of pseudodisaccharides were required having
the a1!1 glycosidic linkage, the reaction of acceptors 5, 6
and 7 with 2-azido-2-deoxy-d-glucopyranosyl trichloroaceti-
midates, afforded anomeric mixtures containing a considera-
ble amount of the b-anomers.[11c,g,h] By contrast, the a1!2
glycosidic linkage in the same d-chiro series and the a1!3
glycosidic linkage in the l-chiro series[11i] as well as the a1!6
glycosidic linkage in the d-myo series[11b,e] were formed with
fair to good stereoselectivity under similar experimental
conditions. These results apparently point to the conclusion
that the orientation of the OH acceptor influences the steric
course of the reaction as HO-1 has, in the chiro series, an
axial-like orientation, whereas HO-2 and HO-3 in this series
It was expected[10a] that, according to the principle of double
stereodifferentiation,[10b] the comparative study on the glyco-
sylation of enantiomeric cyclitols with glycosyl donors carry-
ing the 2-azido function should give additional information
on the role of the glycosyl acceptor, particularly on the in-
fluence of steric factors in the selectivity of the process.
Compound 9, the enantiomer of 5, was synthesized from d-
myo-inositol[12] and compounds 10 and 11, the enantiomers
of 6 and 7, respectively, from l-quebrachitol following the
protocol described for the preparation of 6 and 7 from d-
chiro-inositol (Figure 3).[11g]
Figure 3. l-chiro-inositol glycosyl acceptors.
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M. B. Cid, M. Martꢀn-Lomas, and F. Alfonso
Table 1. Glycosylation of enantiomers 5 and 9. Reaction conditions, reac-
tion products and yields (%).
The stereochemical course of the glycosylation of these l-
chiro-inositol derivatives was investigated under the same
experimental conditions previously established for the glyco-
sylation of the corresponding d-enantiomers. A general view
of the reactions discussed is given in Scheme 1.
Donors
Reaction
Acceptors
conditions
5
9
(d series)
(l series)
12
13
14
1 equiv acceptor, 1.3 equiv donor
0.1 equiv TMSOTf,
15a (44)
15b (31)
16a (65)
16b (15)
The glycosylation of
9 with glycosyl donors 12–14
(Figure 4) was studied under the same experimental condi-
tions as used before for the glycosylation of the d-enantiom-
er 5.[11c] These experimental conditions had been previously
established, from a preparative point of view, to obtain the
a pseudodisaccharides 15a, 17a and 19a as the main prod-
ucts from each of the glycosyl donors investigated.
CH2Cl2, rt, 1 h
1.6 equiv acceptor, 1 equiv donor
0.06 equiv TMSOTf, CH2Cl2,
ꢀ258C (30 min) to rt (10 min)
1 equiv acceptor, 1.5 equiv donor
0.03 equiv TMSOTf, CH2Cl2, rt, 4.5h
17a (35)
17b (25)
18a (42)
18b (42)
19a (49)
19b (21)
20a (47)
20b (5)
also observed in the l series, the results were indicative of a
higher a selectivity in the case of the l-enantiomers. Howev-
er, in this case, under the same experimental conditions, the
steric course of the reaction leading to the l-chiro com-
pounds 16a and 16b, 18a and 18b, 20a and 20b, seemed to
essentially depend on the structure of the glycosyl donor,
the most reactive tri-O-benzyl trichloroacetimidate 13 lead-
ing to the less stereoselective reaction (Figure 5).
The glycosylation of the conformationally constrained l-
chiro-inositols 10 and 11 was next investigated in the condi-
tions previously used by us to obtain pseudodisaccharides
23a, 30a, 27 and 34 as the main products by coupling the d-
enantiomers 6 and 7 with trichloroacetimidates 13 and 21.
Also, the course of the glycosylation of the enantiomeric
pair 6 and 10 with trichloroacetimidate 14 under similar ex-
perimental conditions was examined (Figure 6). The struc-
tures of glycosyl acceptors 6–10 contain two equivalent ax-
ially oriented hydroxyl groups and therefore diglycosylated
pseudotrisaccharides could be formed as minor products
under the reaction conditions.
Figure 4. Glycosyl donors.
The results—which should be taken only as a qualitative
indication of stereochemical outcome of these reactions as
all experiments have been performed on a preparative basis
and the yields calculated based on weight of isolated prod-
ucts—are summarized in Table 1 which also shows the re-
sults previously obtained for 5.[11c] Although in general
terms, the poor selectivity of the process in the d series was
Scheme 1.
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Glycosylation Reactions
FULL PAPER
date 13, which had shown poor stereoselectivity in the d-
chiro series, showed no stereoselectivity in the l-chiro series
and compounds 25a and 25b and 32a and 32b were isolated
in similar proportions. However, as for the d-chiro com-
pounds, excellent stereoselectivity was observed with the
per-O-acetylated donor with d-galacto configuration 21,
compounds 29 and 36 being isolated as the only reaction
products. These results parallel those already obtained for
the conformationally restricted 3-O-methyl-d-chiro-inositol
(d-pinitol) derivative 37 which gave a 2:1 38a, 38b mixture
when reacting with 13, and 39 as the sole pseudodisacchar-
ide when reacting with the perbenzylated trichloroacetimi-
date 22 (Figure 7).[11h]
As in the glycosylation of 5 and 9 with donor 14 (Table 1),
the stereoselectivity of the reaction of 6 and 10 with donor
14 was higher than that observed in the glycosylation of
these diols with donor 13. Also, in this case, the glycosyla-
tion of the l-chiro compound 10, which afforded 41 as the
sole product, was more stereoselective than that of the d-
chiro derivative 6 which gave a mixture of 40a and 40b
(Figure 7). Noteworthy, the a,a-pseudotrisaccharides 24 and
31, respectively, could be isolated in the glycosylation of 6
and 7 with trichloroacetimidate 13 while the coupling of
their enantiomers 10 and 11 with the same donor afforded
the b,b-pseudotrisaccharides 26 and 33 in similar yields.
Also, in the reaction mixtures of the coupling of d-galacto
Figure 5. Pseudodisaccharides resulting from reaction of donors 12, 13
and 14 with acceptors 5 and 9.
Table 2 summarizes the results in comparison with those
previously reported by us for the d-chiro series.[11g] Glycosy-
lations with the per-O-benzylated d-glucotrichloroacetimi-
Figure 6. Pseudodisaccharides resulting from reaction of donors 13 and 21 with acceptors 6,7,10 and 11.
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M. B. Cid, M. Martꢀn-Lomas, and F. Alfonso
groups of compounds belonging to either series occurs with
good selectivity in most of the cases studied,[11i] the stereo-
chemical outcome of the glycosylation of their axially ori-
ented counterparts much more strongly depends on the
structure and the reactivity of the donor.
But even the role of the orientation of the acceptor OH
group is difficult to assess as was demonstrated by the fol-
lowing model study. In this study the stereochemistry of the
glycosylation of trans- (42) and cis- (43) 4-tert-butyl cyclo-
hexanol with trichloroacetimidates 13, 14 and 44 was investi-
gated by using experimental conditions similar to those in
the experiments summarized in Tables 1 and 2. The results
are shown in Figure 8 and Table 3.
In the cases of glycosyl donors 13 and 44 both glycosides
45a and 45b and 46a and 46b were formed but the stereo-
chemistry was always predominantly b. As expected accord-
ing to the reaction conditions, the configuration of the leav-
ing group did not seem to have any effect on the selectivity.
In the case of glycosyl donor 14, glycosides 47a and 47b and
48a and 48b were formed as well but the stereochemistry
was predominantly a. There-
Figure 7. Pseudodisaccharides resulting from reaction of donors 13 and
21 with acceptors 6, 7, 10 and 11.
fore, all other things being
Table 2. Glycosylation of enantiomers 6 and 10 and 7 and 11. Reaction products and yields (%).
equal, it seems to be the glyco-
syl donor that mainly dictates
the stereochemical course of
the glycosylations in these spe-
cific cases.
Donor
Acceptor
7
(d series)
6
10
11
37
(d series)
(l series)
(l series)
(d-pinitol)
A
23a (42)
23b (18)
24 (7)
A
25a (26)
25b (26)
26 (5)
A
30a (43)
30b (20)
31 (5)
A
32a (18)
32b (23)
33 (9)
B
38a (36)
38b (18)
13
The configuration of the ac-
ceptor also seems to play a role
as evidenced in some of the re-
sults shown in Tables 1 and 2,
particularly the glycosylation of
5 and 9 (Table 1) and that of 6
and 10 (Table 2) with trichlor-
oacetimidate 14. Both in the
case of the less sterically con-
strained 5 and 9 and in that of
the conformationally restricted
6 and 11, the glycosylations oc-
curred with higher a stereose-
lectivity in the l-chiro series.
C
27a (51)
28 (14)
C
C
34a (52)
35 (11)
C
21
22
29 (37)
36 (69)
D
39 (46)
E
40a (22)
40b (6)
E
14
41 (56)
[a] A: 1 equiv acceptor, 1.6 equiv donor, 0.1 equiv TMSOTf, CH2Cl2, ꢀ258C, 1 h. B: 1 equiv acceptor, 1.5 equiv
donors, 0.08 equiv TMSOTf, CH2Cl2, rt. C: 1 equiv acceptor, 2 equiv donor, 0.1 equiv TMSOTf, CH2Cl2, rt, 1 h.
D: 1 equiv acceptor, 1.3 equiv donor, 0.15 equiv TMSOTf, CH2Cl2/Hex, ꢀ408C. E: 1 equiv acceptor, 1.5 equiv
donor, 0.03 equiv TMSOTf, CH2Cl2, rt, 4.5 h.
Table 3. Glycosylation of 42 and 43. Reaction products and yields (%).[a]
configurated trichloroacetimidate 21 the a,a-pseudotrisac-
charides 28 and 35 were found whereas no formation of
pseudotrisaccharide was observed in the glycosylation of
their enantiomers (10 and 11) with the same donor.
Acceptor
Donors
13
44
14
42
43
45a (12)
45b (52)
46a (12)
46b (37)
45a (17)
45b (51)
46a (13)
46b (42)
47a (48)
47b (17)
48a (48)
48b (22)
It can be concluded that the stereoselectivity of these gly-
cosylations of axially oriented hydroxyl groups of chiro-ino-
sitol derivatives, either of the d or the l series, with various
protection patterns and different conformational flexibility
and under similar experimental conditions, strongly depends
on the structure of the 2-azido-2-deoxy trichloroacetimidate
donor and on the orientation and, to some extent, the abso-
lute configuration of the OH acceptor but not, to an impor-
tant extent, on the conformational constrain of the inositol
ring. While glycosylation of equatorially oriented OH
[a] Reaction conditions: 1 equiv acceptor, 1.2 equiv donor, CH2Cl2,
0.1 equiv TMSOTf, ꢀ258C, 1 h.
This glycosyl donor gave a good stereoselectivity in all
cases, most likely as a result of the flattening and the restric-
tion of the conformational flexibility of the pyranoid ring,
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Glycosylation Reactions
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quires considerable experimen-
tation. Only a careful investiga-
tion of the effect of reaction
conditions, solvent, temperature
and promoter, and the choice
of a glycosyl donor that, fitting
the synthesis needs, matches its
reactivity–selectivity
require-
ments with those of the given
acceptor may permit to achieve
the desired stereochemistry.
Two very recent cases in the
field of glycosaminoglycan syn-
thesis have clearly shown that
undesired stereochemical sur-
prises may arise when a glyco-
sylation step with a 2-azido-2-
deoxy glycosyl donor is in-
Figure 8. Pseudodisaccharides resulting from reaction of donors 13, 44 and 14 with cyclohexenol acceptors 42
and 43.
caused by the benzylidene ring, which may also favor the
axial nucleophilic attack.[14]
volved at the late stage of a complex synthetic process.[15]
The interesting results by Seeberger et al.[7] on the confor-
mational locking of the acceptor for stereocontrol of glyco-
sylations with these glycosyl donors and the impressive dem-
onstration by Spijker and van Boeckel of the double stereo-
differentiation in carbohydrate coupling reactions[10a] consti-
tute brilliant demonstrations of principles whose practical
consequences can be clearly observed only in particularly fa-
vorable cases.
The glycosylations with the per-O-acetylated trichloroace-
timidate with the d-galacto configuration 21 occurred with
excellent stereoselectivity and those with the per-O-benzy-
lated trichloroacetimidate with the d-gluco configuration 13
gave very poor results. It is known that the long range par-
ticipation of the 4-OH group of glycosyl donors with the gal-
4
acto configuration may stabilize the C1 conformation of the
pyranoid ring thus favoring axial nucleophilic attack on the
intermediate glycosyl oxocarbenium ion.[13] But the system
is too complex to draw precise conclusions on the relative
influence of the factors governing the stereochemistry of
these glycosylations, particularly when using reactive donors
with the d-gluco configuration.
Experimental Section
General remarks: Diethyl ether and dichloromethane were distilled from
sodium/benzophenone and calcium hydride, respectively. 4-tert-Butylcy-
clohexanol was purchased from Aldrich as a mixture of isomers that was
separated by flash chromatography (hexane/ethyl acetate 4:1) to give
pure cis-tert-butylcyclohexanol and trans-4-tert-butylcyclohexanol. Molec-
ular sieves (4 ꢅ, powered) was dried in the oven at 1008C and activated
for 5 min under vacuum at 5008C. All reactions were run under an at-
mosphere of dry argon using oven-dried glassware and freshly distilled
and dried solvents unless otherwise stated. TLC was performed on silica
gel GF254. Silica gel (230–400 mesh) was used for flash chromatography
and eluents are given as volume to volume ratios (v/v). All aqueous solu-
tions were saturated unless otherwise stated. 1H (300, 400 and 500 MHz)
and 13C (125 and 75 MHz) NMR spectra were recorded at 258C in
CDCl3 unless otherwise noted, chemical shifts are given in ppm relative
to CDCl3 (7.27 ppm) and coupling constants are reported in Hz. Reso-
nances were assigned by means of 2D spectra (COSY, HMQC).
Conclusion
In summary, we have examined the steric course of the gly-
cosylation of the relatively unreactive axially oriented hy-
droxyl groups of d- and l-chiro inositol derivatives with 2-
azido-2-deoxy-d-gluco- and d-galactopyranosyl trichloroace-
timidates. The influence of the absolute configuration of the
acceptor and the conformational flexibility and substitution
pattern of both donor and acceptor on the stereoselectivity
of the reaction has been investigated. The effect of the ori-
entation of the acceptor hydroxyl group and the orientation
of the leaving group of the donor have been further studied
by using cis- and trans-4-hydroxy-tert-butyl cyclohexanol and
a- and b-trichloroacetimidates. The results indicate that the
influence of the absolute configuration, the orientation of
the acceptor OH group and the conformational constrain of
the acceptor on the stereochemical outcome of the reaction
are difficult to asses and the existing data in the literature
difficult to rationalize. According to our data, it is the struc-
ture of the glycosyl donor that always plays the major role.
The control of the stereochemical course of these glycosyla-
tions with 2-azido-2-deoxy-trichloroacetimidates still re-
2-Azido-3,4,6-tri-O-acetyl-2-deoxy-d-glucopyranosyl-a-(1!1)-6-O-allyl-
2,3,4,5-tetra-O-benzyl-l-chiro-inositol (16a) and 2-azido-3,4,6-tri-O-
acetyl-2-deoxy-d-glucopyranosyl-b-(1!1)-6-O-allyl-2,3,4,5-tetra-O-
benzyl-l-chiro-inositol (16b): A mixture of 2-azido-3,4,6-tri-O-acetyl-2-
deoxy-d-glucopyranosyl trichloroacetimidate (12) (86 mg, 0.181 mmol)
and 9 (35 mg, 0.06 mmol) was co-evaporated with toluene (3ꢆ), 4 ꢅ mo-
lecular sieves was added and the residue dried under vacuum overnight.
The mixture was dissolved in CH2Cl2 (2 mL) under argon and stirred at
room temperature for 30 min, then TMSOTf (0.1 equiv, 28.5 mL of a so-
lution 0.2m in CH2Cl2) was added at rt. After 1 h the reaction mixture
was quenched with Et3N, concentrated and purified by flash chromatog-
raphy (cyclohexane/ethyl acetate 3:1) to yield 16a (36 mg, 65%) and 16b
(8 mg, 15%). 16a: [a]D
=
+78.5 (c=1.6, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.40–7.20 (m, 20H, 4Bn), 5.78–5.71 (m, 1H, CH vinylic), 5.43
(d, 1H, J=3.8 Hz, H1’), 5.22 (t, 1H, J=9.9 Hz, H3’), 5.11 (m, 2H, CH2 vi-
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M. B. Cid, M. Martꢀn-Lomas, and F. Alfonso
nylic), 4.96 (t, 1H, J=9.9 Hz, H4’), 4.98–4.58 (4AB, 8H), 4.17 (dd, 1H,
J=12.3, 4.6 Hz, H6’a), 4.08 (dd, 1H, J=10.3, 6.0 Hz, CH allylic), 3.96 (t,
1H, J=9.5 Hz, H3 or H4), 3.92 (brt, 1H, J=2.9 Hz, H1 or H6), 3.90–3.83
(m, 2H, CH allylic, H6’b), 3.82 (t, 1H, J=9.5 Hz, H4 or H3), 3.77 (dd, 1H,
J=9.5, 2.9 Hz, H2 or H5), 3.72 (dd, 1H, J=9.5, 3.1 Hz, H5 or H2), 3.50
(m, 1H, H5’), 3.34 (dd, 1H, J=9.9, 3.8 Hz, H2’), 3.23 (t, 1H, J=3.1 Hz, H6
or H1), 2.10 (3s, 9H, 3OCOCH3); 13C NMR (125 MHz, CDCl3): d=170.8
(OCOCH3), 170.1 (OCOCH3), 169.8 (OCOCH3), 139.3 (C), 139.2 (C),
138.9 (C), 138.7 (C), 135.0 (CH vinylic), 128.9–127.7 (20CH, Bn), 117.6
(CH2 vinylic), 98.4 (C1’), 82.3 (CH), 81.8 (CH), 79.8 (CH), 79.4 (CH),
76.7 (CH), 76.2 (2CH2), 74.5 (CH2), 74.2 (CH2), 74.0 (CH), 72.5 (CH2),
70.3 (CH), 68.8 (CH), 68.0 (CH), 62.1 (CH2), 61.4 (CH), 21.1
(OCOCH3), 21.0 (OCOCH3), 20.9 (OCOCH3); FAB HRMS: m/z: calcd
for C49H55O13N3Na: 916.3632; found: 916.3645 [M+Na]+.
2-Azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-d-glucopyranosyl-a-(1!
1)-6-O-allyl-2,3,4,5-tetra-O-benzyl-d-chiro-inositol (19a) and 2-azido-3-
O-benzyl-4,6-O-benzylidene-2-deoxy-d-glucopyranosyl-b-(1!1)-6-allyl-
2,3,4,5-tetra-O-benzyl-d-chiro-inositol (19b): The pseudodisaccharides
were prepared from 14 (520 mg, 0.985 mmol) and 5 (382 mg, 0.657 mmol)
as described for the preparation of 16a and 16b, adding at rt TMSOTf
(0.1 equiv, 350 mL of a solution 0.2m) and stirring the reaction mixture
for 4.5 h at rt, yielding after flash chromatography (hexane/ethyl acetate
8:1) 19a (302 mg, 49%) and 19b (130.5 mg, 21%). 19a: [a]D
= +5.6
(c=1.2, CHCl3); 1H NMR (500 MHz, CDCl3): d=7.47–7.21 (m, 30H,
6Bn), 5.79 (m, 1H, CH vinylic), 5.51 (s, 1H, CHPh), 5.17 (m, 1H, CH vi-
nylic), 5.13 (m, 1H, CH2 vinylic), 4.97–4.76 (5 AB, 10H), 4.70 (d, 1H, J=
3.8 Hz, H1’), 4.25–4.17 (m, 2H, H5’, CH allylic), 3.99 (t, 1H, J=9.4 Hz,
H3’), 3.97 (m, 1H, CH allylic), 3.95 (m, 1H, H6’a), 3.97–3.74 (m, 6H, H1,
H2, H3, H4, H5, H6), 3.64 (t, 1H, J=9.4 Hz, H4’), 3.56 (t, 1H, J=10.3 Hz,
Compound 16b: [a]D
=
ꢀ4.0 (c=0.4, CHCl3); 1H NMR (500 MHz,
H
6’b), 3.49 (dd, 1H, J=9.4, 3.8 Hz, H2’); 13C NMR (125 MHz, CDCl3): d=
CDCl3): d=7.40–7.20 (m, 20H, 4Bn), 5.77 (m, 1H, CH vinylic), 5.14 (m,
2H, CH2 vinylic), 4.98 (m, 2H, H1’ and H6’a), 4.89–4.62 (4 AB syst, 8H),
4.23 (m, 3H, CH allylic, H3’ and H6’b), 4.12 (brs, 1H, H1 or H6), 4.09 (t,
1H, J=10.3 Hz, H4’), 3.95 (dd, 1H, J=13.0, 6.2 Hz, CH allylic), 3.86–3.80
(m, 4H, H2, H3, H4, H5), 3.76 (brs, 1H, H6 or H1), 3.57 (brt, 1H, J=
9.3 Hz, H2’), 3.53 (m, 1H, H5’), 2.10 (s, 3H, OCOCH3), 2.00 (s, 6H,
2OCOCH3); 13C NMR (125 MHz, CDCl3): d=170.9 (OCOCH3), 170.4
(OCOCH3), 169.8 (OCOCH3), 139.3 (2C), 138.8 (C), 138.6 (C), 135.2
(CH vinylic), 128.7–127.7 (20CH, Bn), 117.5 (CH2 vinylic), 100.7 (C1’),
82.0 (CH), 81.9 (CH), 80.2 (CH), 78.5 (CH), 77.7 (CH), 76.2 (2CH2), 75.2
(CH), 74.2 (CH), 73.8 (CH2), 73.3 (CH2), 73.0 (CH), 72.5 (CH2), 68.6
(CH), 63.9 (CH), 62.4 (CH2), 30.0 (OCOCH3), 21.0 (OCOCH3), 20.9
(OCOCH3); FAB HRMS: m/z: calcd for C49H55O13N3Na: 916.3632;
found: 916.3637.
139.3 (C), 139.2 (C), 139.1 (C), 138.7 (C), 138.2 (C), 137.7 (C), 135.2 (CH
vinylic), 129.3–126.3 (30CH, Bn), 117.5 (CH2 vinylic), 101.6 (CHPh), 98.0
(C1’), 83.2 (CH), 82.6 (CH), 82.1 (CH), 80.3 (CH), 78.5 (CH), 77.6 (CH),
76.4 (CH2), 76.1 (CH2), 75.5 (CH2), 75.5 (CH), 74.1 (CH), 73.7 (CH2),
73.7 (CH2), 72.8 (CH2), 69.1 (CH2), 63.7 (CH), 63.2 (CH); FAB HRMS:
m/z: calcd for C57H59O10N3Na: 968.4098; found: 968.4091 [M+Na]+.
Compound 19b: 1H NMR (500 MHz, CDCl3): d=7.50–7.20 (m, 30H,
6Bn), 5.74 (m, 1H, CH vinylic), 5.54 (s, 1H, CHPh), 5.15 (m, 1H, CH vi-
nylic), 5.11 (m, 1H, CH vinylic), 4.90–4.60 (5 AB syst, 10H), 4.54 (d, 1H,
J=8.1 Hz, H1’), 4.21 (dd, 1H, J=10.4, 5.1 Hz, H6’a), 4.13 (m, 1H, CH al-
lylic), 3.92–3.74 (m, 6H, H1, H2, H3, H4, H5, H6), 3.70 (t, 1H, J=9.3 Hz,
H6’a), 3.61 (t, 1H, J=9.3 Hz, H4’), 3.46 (t, 1H, J=9.4 Hz, H3’), 3.28 (t,
1H, J=8.1 Hz, H2’), 3.23 (dd, 1H, J=9.3, 5.1 Hz, H5’); 13C NMR
(125 MHz, CDCl3): d=139.4 (C), 139.3 (C), 138.9 (C), 138.8 (C), 137.9
(C), 137.5 (C), 135.3 (CH vinylic), 129.9–127.2 (30CH, Bn), 117.2 (CH2
vinylic), 103.2 (C1’), 101.7 (CHPh), 82.1, 81.8, 81.6, 79.9, 79.7, 78.8, 76.1,
76.1, 76.0, 75.9, 75.7, 75.2, 73.8, 73.4, 72.5, 68.8, 66.2 (CH); FAB HRMS:
m/z: calcd for C57H59O10N3Na: 968.4098; found: 968.4089.
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranosyl-a-(1!1)-6-O-allyl-
2,3,4,5-tetra-O-benzyl-l-chiro-inositol (18a) and 2-azido-3,4,6-tri-O-
benzyl-2-deoxy-d-glucopyranosyl-b-(1!1)-6-allyl-2,3,4,5-tetra-O-benzyl-
l-chiro-inositol (18b): The pseudodisacharides were prepared from 13
(50 mg, 0.08 mmol) and 9 (74 mg, 0.129 mmol) in dry CH2Cl2 (1 mL), as
described for the preparation of 16a and 16b adding TMSOTf
(0.06 equiv, 50 mL of a solution 0.1m) at ꢀ258C and stirring the reaction
mixture for 30 min at ꢀ258C, and 10 min at rt, yielding after flash chro-
matography (hexane/diethyl ether 4:1) 18a (35 mg, 42%) and 18b
(35 mg, 42%). 18a: [a]D = +48.2 (c=1.7, CHCl3); 1H NMR (500 MHz,
C6D6): d=7.50–7.10 (m, 35H, 7Bn), 5.96–5.86 (m, 1H, CH vinylic), 5.50
(d, 1H, J=3.8 Hz, H1’), 5.29 (dd, 1H, J=17.2, 1.6 Hz, CH vinylic), 5.23–
4.41 (7AB syst, 14H), 5.11 (dd, 1H, J=17.2, 1.6 Hz, CH vinylic), 4.43 (t,
1H, J=9.5 Hz, H4), 4.34–4.30 (m, 2H, CH allylic, H6), 4.28 (t, 1H, J=
9.5 Hz, H3), 4.14 (m, 1H, H5), 4.12 (m, 1H, H2), 4.07–4.02 (m, 1H, CH al-
lylic), 4.00 (t, 1H, J=9.3 Hz, H3’), 3.95 (brt, 1H, J=3.1 Hz, H1), 3.94–
3.89 (m, 1H, H5’), 3.76–3.67 (m, 2H, H6’a, H6’b), 3.57 (t, 1H, J=9.3 Hz,
H4’), 3.13 (dd, 1H, J=9.3, 3.8 Hz, H2’); 13C NMR (125 MHz, C6D6): d=
140.5 (C), 139.8 (2C), 139.4 (C), 139.3 (C), 139.2 (C), 138.6 (C), 136.2
(CH vinylic), 129.3–128.0 (35CH, Bn), 117.1 (CH2 vinylic), 99.7 (C1’),
83.1 (CH), 83.0 (CH), 80.8 (CH), 80.5 (2CH), 79.5 (CH), 77.5 (C1), 76.5
(CH2), 75.9 (CH2), 75.8 (CH2), 74.8 (CH), 74.3 (2CH2), 74.1 (CH2), 73.5
(CH2), 72.7 (CH), 70.1 (CH2), 69.0 (CH2), 64.5 (CH); FAB HRMS: m/z:
calcd for C64H67O10N3Na: 1060.4724; found: 1060.4668 [M+Na]+.
2-Azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-d-glucopyranosyl-a-(1!
1)-6-O-allyl-2,3,4,5-tetra-O-benzyl-l-chiro-inositol (20a) and 2-azido-3-
O-benzyl-4,6-O-benzylidene-2-deoxy-d-glucopyranosyl-b-(1!1)-6-allyl-
2,3,4,5-tetra-O-benzyl-l-chiro-inositol (20b): The pseudodisaccharides
were prepared from 14 (71 mg, 0.134 mmol) and 9 (52 mg, 0.09 mmol) in
dry CH2Cl2 (1 mL) as described for the preparation of 16a and 16b
adding at rt TMSOTf (0.1 equiv, 13.95 mL of a solution 0.2m) and stirring
the reaction mixture for 4.5 h, yielding after flash chromatography
(hexane/ethyl acetate 8:1) 20a (40 mg, 47%) and 20b (4 mg, 5%). 20a:
[a]D
=
+39.6 (c=2.0, CHCl3); 1H NMR (500 MHz, CDCl3): d=7.50–
7.10 (m, 30H, 6Bn), 5.81–5.72 (m, 1H, CH vinylic), 5.57 (s, 1H, CHPh),
5.37 (d, 1H, J=3.8 Hz, H1’), 5.18–5.12 (m, 2H, CH2 vinylic), 4.98–4.60 (5
AB syst, 10H), 4.15 (dd, 1H, J=10.4, 4.9 Hz, H6’a), 4.09 (m, 1H, CH al-
lylic), 4.01 (t, 1H, J=9.5 Hz, H4), 3.96 (brs, 1H, H6), 3.92 (m, 1H, CH al-
lylic), 3.85 (t, 1H, J=9.5 Hz, H3), 3.82–3.69 (m, 4H, H3’, H5, H2, H6’b),
3.65 (t, 1H, J=9.3 Hz, H4’), 3.58–3.52 (m, 1H, H5’), 3.47 (brs, 1H, H1),
3.36 (dd, 1H, J=9.9, 3.8 Hz, H2’); 13C NMR (125 MHz, CDCl3): d=139.4
(C), 139.3 (C), 138.8 (C), 138.6 (C), 138.2 (C), 137.5 (C), 135.1 (CH vinyl-
ic), 129.4–126.2 (30CH, Bn), 117.8 (CH2 vinylic), 101.6 (CHPh), 99.1
(C1’), 82.8 (CH), 82.3 (CH), 81.9 (CH), 80.1 (CH), 79.4 (CH), 76.3 (CH2),
76.2 (CH2), 76.1 (CH), 75.8 (C1), 75.5 (CH2), 73.9 (2CH2), 73.3 (CH),
72.4 (CH2), 69.0 (CH2), 63.5 (CH), 63.4 (CH); FAB HRMS: m/z: calcd
for C57H59O10N3Na: 968.4098; found: 968.4108 [M+Na]+.
Compound 18b: [a]D
=
ꢀ6.1 (c=1.7, CHCl3); 1H NMR (500 MHz,
C6D6): d=7.50–7.10 (m, 35H, 7Bn), 5.96–5.87 (m, 1H, CH vinylic), 5.31
(dd, 1H, J=17.2, 1.6 Hz, CH vinylic), 5.20–4.55 (7AB syst, 14H), 5.13
(dd, 1H, J=17.2, 1.6 Hz, CH vinylic), 4.56 (brt, 1H, J=3.4 Hz, H1 or
H6), 4.45 (m, 2H, CH allylic and H2 or H5), 4.40–4.30 (m, 2H, H3, H4),
4.28 (d, 1H, J=7.7 Hz, H1’), 4.22 (dd, 1H, J=9.3, 3.4 Hz, H5 or H2), 4.10
(m, 2H, CH allylic and H6 or H1), 3.66 (m, 3H, H4’, H6’a, H6’b), 3.43 (m,
2H, H2’ and H3’), 3.30 (m, 1H, H5’); 13C NMR (125 MHz, C6D6): d=140.7
(C), 140.6 (C), 140.1 (C), 140.0 (C), 139.4 (C), 139.3 (C), 139.2 (C), 136.1
(CH vinylic), 129.1–128.0 (35CH, Bn), 117.1 (CH2 vinylic), 101.5 (C1’),
84.0 (CH), 83.0 (2CH), 81.3 (CH), 79.5 (CH), 78.7 (CH), 76.5 (CH2), 76.4
(CH), 76.2 (CH2), 76.1 (CH2), 75.8 (CH), 75.5 (CH), 75.1 (CH2), 74.5
(CH2), 74.3 (CH2), 73.7 (CH2), 73.1 (CH2), 69.8 (CH2), 67.3 (CH); FAB
HRMS: m/z: calcd for C64H67O10N3Na: 1060.4724; found: 1060.4695.
Compound 20b: [a]D
=
ꢀ23.0 (c=0.2, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.50–7.20 (m, 30H, 6Bn), 5.80–5.70 (m, 1H, CH vinylic), 5.60
(s, 1H, CHPh), 5.15–5.08 (m, 2H, CH2 vinylic), 4.94–4.63 (5 AB syst,
10H), 4.33 (dd, 1H, J=10.4, 4.9 Hz, H6’a), 4.17 (m, 1H, CH allylic), 4.15
(d, 1H, J=8.2 Hz, H1’), 3.98 (brt, 1H, J=3.1 Hz, H6), 3.92 (m, 1H, CH
allylic), 3.88–3.77 (m, 6H, H6’b, H2, H3, H4, H5, H1), 3.76 (t, 1H, J=
9.3 Hz, H4’), 3.60 (t, 1H, J=9.2 Hz, H3’), 3.50 (dd, 1H, J=9.2, 8.2 Hz,
H2’), 3.36–3.30 (m, 1H, H5’); 13C NMR (125 MHz, CDCl3): d=139.4 (C),
139.3 (C), 139.0 (C), 138.8 (C), 137.9 (C), 137.4 (C), 135.2 (CH vinylic),
129.5–126.3 (30CH, Bn), 117.3 (CH2 vinylic), 101.7 (CHPh), 101.6 (C1’),
82.1 (CH), 81.6 (CH), 80.3 (CH), 79.9 (C1H), 78.5 (CH), 77.1 (CH2), 77.0
934
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 928 – 938

Glycosylation Reactions
FULL PAPER
(CH), 76.3 (CH2), 76.2 (CH), 75.1 (CH2), 74.4 (CH), 73.7 (2CH2), 72.9
(CH2), 68.8 (CH2), 66.8 (CH), 65.9 (CH); FAB HRMS: m/z: calcd for
C57H59O10N3Na: 968.409; found: 968.4100.
di(2-azido-3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranosyl)-b,b-(1!1:1!6)-
2,5-di-O-benzyl-3,4-O-(2’,3’-dimethoxy-butane-2’,3’-diyl)-l-chiro-inositol
(26): The pseudosaccharides were prepared from 13 (64 mg, 0.104 mmol)
and 10 (31 mg, 0.065 mmol) as described for the preparation of 16a and
16b, adding TMSOTf (0.1 equiv, 0.65 mL of a solution 0.01m) at ꢀ258C,
in CH2Cl2 (2 mL) and stirring the reaction mixture for 1 h, yielding after
flash chromatography (hexane/ethyl acetate 4:1) 25a (16 mg, 25%), 25b
2,5-Di-O-benzyl-3,4-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-l-chiro-inositol
(10): The compound has been prepared following the same experimental
procedure described for its d-enantiomer 6 in ref. [11g]. [a]D = ꢀ79.6
(c=1, CHCl3).
(15 mg, 25%), and b,b-pseudotrisaccharide 26 (5 mg, 5%). 25a: [a]D
=
2,3:4,5-Di-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-l-chiro-inositol (11): The
ꢀ1.5 (c=1.4, CHCl3); 1H NMR (500 MHz, CDCl3): d=7.40–7.10 (m,
25H, 5Bn), 5.44 (d, 1H, J=3.8 Hz, H1’), 4.96–4.45 (5 AB syst, 10H), 4.28
(t, 1H, J=10.3 Hz, H3), 4.22 (brt, 1H, J=3.5 Hz, H1), 4.02 (t, 1H, J=
9.9 Hz, H4), 3.89 (dd, 1H, J=10.3, 3.5 Hz, H2), 3.87 (brt, 1H, J=3.5 Hz,
H6), 3.75 (dd, 1H, J=8.2, 3.5 Hz, H5), 3.74–3.55 (m, 5H, H3’, 2H6’, H4’,
H5’), 3.38 (dd, 1H, J=10.1, 3.8 Hz, H2’), 3.31, 3.30 (2s, 6H, 2OCH3), 2.50
(s, 1H, C6OH), 1.39, 1.34 (2s, 6H, 2CH3); 13C NMR (125 MHz, CDCl3):
d=139.5, 138.7, 138.4, 138.2, 138.1 (5C, Bn), 128.8–127.4 (25CH, Bn),
99.7, 99.5 (2C BDA), 98.8 (C1’), 80.3, 78.4, 77.1, 76.6, 75.7, 75.6, 75.2,
74.3, 74.2, 74.0, 71.4, 71.2, 70.5, 69.8, 68.5, 64.2 (10CH, 6CH2), 48.1
(2OCH3), 18.3, 18.2 (2CH3); elemental analysis calcd (%) for
compound has been prepared following the same experimental procedure
described for its d-enantiomer 7 in ref. [11g]. [a]D
= +135.3 (c=1,
CHCl3).
Di(2-azido-3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranosyl)-a,a-1!1:1!6)-
2,5-di-O-benzyl-3,4-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-d-chiro-inositol
(24): Prepared by reaction of acceptor 6 with donor 13. [a]D20
= +48.4
(c=0.7, CHCl3); 1H NMR (500 MHz, CDCl3): d=7.34–7.03 (m, 40H,
8Ph), 4.86–4.81 (m, 4H, 4CHPh), 4.76 (d, 2H, JH1’,H2’ =3.6 Hz, 2H1’),
4.67–4.10 (m, 12H, 12CHPh), 4.02–3.98 (m, 4H, H1, H3, H4, H6), 3.93–
3.90 (m, 2H, H2, H5), 3.80 (dd, 2H, JH3’,H2’ =10.1, JH3’,H4’ =9.6 Hz, 2H3’),
3.68 (dd, 2H, JH4’,H3’ =10.1, JH4’,H5’ =9.5 Hz, 2H4’), 3.47 (dd, 2H, JH2’,H3’
10.1, JH2’,H1’ =3.6 Hz, 2H2’), 3.33 (s, 6H, 2OCH3), 3.23 (dd, 2H, JH6’a,H6’b
=
C53H61O12N3+1= H2O: C 67.64, H 6.64, N 4.46; found: C 67.60, H 7.07, N
=
2
4.10.
11.1, JH6’a,H5’ =2.0 Hz, 2H6’a), 3.03 (dd, 2H, JH6’b,H6’a =11.1, JH6’b,H5’ =1.5 Hz,
Compound 25b: [a]D = ꢀ45.0 (c=0.66, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.38–7.12 (m, 25H, 5Bn), 4.91–4.35 (5 AB syst, 10H), 4.26
(brt, 1H, J=3.6 Hz, H1), 4.19 (d, 1H, J=7.7 Hz, H1’), 4.11 (brt, 1H, J=
3.5 Hz, H6), 4.07 (t, 1H, J=9.9 Hz, H3), 4.00 (t, 1H, J=9.9 Hz, H4), 3.86
(dd, 1H, J=9.9, 3.4 Hz, H5), 3.83 (dd, 1H, J=10.0, 3.6 Hz, H2), 3.61–3.55
(m, 3H, H6’b, H4’, H3’), 3.45–3.40 (m, 2H, H2’, H6’a), 3.35–3.30 (m, 1H,
H5’), 3.26 (s, 6H, 2OCH3), 2.48 (s, 1H, C6OH), 1.34 (2s, 6H, 2CH3);
13C NMR (125 MHz, CDCl3): d=139.3, 138.5, 137.9, 137.8, 137.7 (5C,
Bn), 128.8–127.4 (25CH, Bn), 101.1 (C1’), 99.4, 99.2 (2C BDA), 83.7
(CH), 77.7 (CH), 76.3 (2CH), 75.4 (CH2), 75.2 (CH), 75.0 (CH2), 74.8
(CH), 73.6 (CH2), 73.5 (CH2), 72.4 (CH2), 69.8 (CH), 69.2 (CH), 68.9
(CH), 68.2 (CH2), 65.8 (CH), 48.1, 47.7 (2OCH3), 17.8 (2CH3); elemental
analysis calcd (%) for C53H61O12N3+H2O: C 67.00, H 6.68, N 4.42; found:
C 67.31, H 6.71, N 4.20.
2H6’b), 1.36 (s, 6H, 2CH3).
Di(3,4,6-tri-O-acetyl-2-azido-2-deoxy-d-galactopyranosyl)-a,a(1!1:1!
6)-2,5-di-O-benzyl-3,4-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-d-chiro-inosi-
tol (28): Prepared by reaction of acceptor 6 with donor 21. [a]2D0 = +47.0
(c=0.4, CHCl3); 1H NMR (500 MHz, CDCl3): d=7.33–7.19 (m, 10H,
2Ph), 5.32 (brd, 2H, JH4’,H3’ =3.2 Hz, 2H4’), 5.20 (dd, 2H, JH3’,H2’ =11,
J
H3’,H4’ =3.2 Hz, 2H3’), 4.93 (AB, 2H, 2CHPh), 4.85 (d, 2H, JH1’,H2’
=
3.5 Hz, 2H1’), 4.64 (AB, 2H, 2CHPh), 4.60 (dd, 2H, JH5’,H6’ =7.1, JH5’,H6’
=
6.9 Hz, 2H5’), 4.05–3.90 (m, 6H, H1, H2, H3, H4, H5, H6), 3.87–3.80 (m,
4H, 2H2’, 2H6’a), 3.57 (dd, 1H, JH6’b,H6’a =10.9, JH6’b,H5’ =6.9 Hz, 2H6’b),
3.34 (s, 6H, 2OCH3), 2.08, 2.03, 1.85 (3s, 18H, 6CH3CO), 1.35 (s, 6H,
2CH3); 13C NMR (75 MHz, CDCl3): d=170.7, 170.4, 170.0 (6CH3CO),
139.7 (2C, Bn), 127.8 (4CH, Bn), 127.6 (4CH, Bn), 127.4 (2CH, Bn),
99.7 (2C, BDA), 96.9 (2C1’), 76.5, 74.5, 74.2 (C1, C2, C5, C6, 2CH2Ph),
71.1 (C3, C4), 70.0 (2C3’), 67.7 (2C4’), 66.8 (2C5’), 61.3 (2C6’), 58.1 (2C2’),
46.5 (2OCH3), 21.1, 21.0 (6CH3CO), 18.3(2CH3).
Compound 26: [a]D
=
ꢀ52.4 (c=0.25, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.40–7.10 (m, 40H, 8Bn), 4.80–4.35 (8AB syst, 16H), 4.24
(d, 2H, H1, H6), 4.16 (d, 2H, J=7.9 Hz, 2H1’), 4.07 (m, 2H, H2, H5), 3.84
(m, 2H, H3, H4), 3.60–3.52 (m, 6H, 4H6’, 2H4’), 3.40–3.27 (m, 6H, 2H2’,
2H3’, 2H5’), 3.33 (s, 12H, 2OCH3), 1.36 (s, 12H, 2CH3); FAB HRMS:
m/z: calcd for C80H88O16N6Na: 1410.6156; found: 1410.6099 [M+Na]+.
Di(2-azido-3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranosyl)-a,a-(1!1:1!6)-
2,3:4,5-di-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-d-chiro-inositol (31): Pre-
pared by reaction of acceptor 7 with donor 13. 1H NMR (500 MHz,
CDCl3): d=7.31–7.17 (m, 30H, 6Ph), 4.87–4.80 (m, 6H, 4CHPh, 2H1’),
4.77–4.41 (m, 8H, 8CHPh), 4.35 (brd, 2H, JH5’,H4’ =9.2 Hz, 2H5’), 3.99–
3.85 (m, 8H, H1, H2, H3, H4 H5, H6, 2H3’), 3.76 (dd, 2H, JH4’,H3’ =9.9,
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranosyl-a-(1!1)-2,3:4,5-di-
O-(2’,3’-dimethoxybutane-2’,3’-diyl)-l-chiro-inositol (32a), 2-azido-3,4,6-
tri-O-benzyl-2-deoxy-d-glucopyranosyl-b-(1!1)-2,3:4,5-di-O-(2’,3’-dime-
thoxybutane-2’,3’-diyl)-l-chiro-inositol (32b) and di(2-azido-3,4,6-tri-O-
benzyl-2-deoxy-d-glucopyranosyl)-b,b-(1!1:1!6)-2,3:4,5-di-O-(2’,3’-di-
methoxybutane-2’,3’-diyl)-l-chiro-inositol (33): The pseudodisaccharides
were prepared from 13 (64 mg, 0.104 mmol) and 11 (27 mg, 0.066 mmol)
as described for the preparation of 16a and 16b, adding TMSOTf
(0.1 equiv, 0.26 mL of a solution 0.025m) at ꢀ258C in CH2Cl2 (2 mL) and
stirring the reaction mixture for 1 h, yielding after flash chromatography
(hexane/ethyl acetate 4:1) 32a (10 mg, 18%), 32b (13 mg, 23%) and b,b-
pseudotrisaccharide 33 (8 mg, 9%). 32a: [a]D = +98.0 (c=0.5, CHCl3);
1H NMR (500 MHz, CDCl3): d=7.40–7.10 (m, 15H, 3Bn), 5.57 (d, 1H,
J=3.8 Hz, H1’), 4.87–4.42 (3AB syst, 6H), 4.16 (t, 1H, J=10.2 Hz, H3),
4.13 (brt, 1H, J=2.9 Hz, H1), 3.95 (dd, 1H, J=9.9, 3.0 Hz, H2), 3.94 (t,
1H, J=10.1 Hz, H4), 3.88 (brt, 1H, J=3.1 Hz, H6), 3.85 (dd, 1H, J=9.9,
2.9 Hz, H5), 3.76–3.63 (m, 5H, H3’, H4’, H5’, 2H6’), 3.37 (dd, 1H, J=9.9,
3.8 Hz, H2’), 3.25, 3.23, 3.16, 3.18 (4s, 12H, 4OCH3), 2.50 (s, 1H, C6OH),
1.30, 1.29, 1.25, 1.18 (4s, 12H, 4CH3); 13C NMR (125 MHz, CDCl3): d=
138.4, 138.3, 138.1 (3C, Bn), 128.8–128.1 (15CH, Bn), 100.6, 100.2, 99.3,
99.0 (4C, BDA), 98.3 (C1’H), 80.1 (CH), 78.4 (CH), 75.7 (CH2), 75.5
(CH2), 73.9 (C1H), 73.6 (CH2), 71.5 (CH), 70.9 (CH), 69.4 (CH), 69.0
(CH), 68.6 (CH2), 66.6 (CH), 66.4 (CH), 60.7 (CH), 48.4, 48.3, 48.2, 48.2
(4C, 2OCH3) and 18.2, 18.1, 18.0, 18.0 (4CH3); elemental analysis calcd
J
H4’,H5’ =9.2 Hz, 2H4’), 3.73 (dd, 2H,
2H6’a), 3.63 (dd, 2H, JH6’b’,H6’a =10.9, JH6’b,H5’ =1.7 Hz, 2H6’b), 3.52 (dd, 2H,
H2’,H3’ =10.0, JH2’,H1’ =3.5 Hz, 2H2’), 3.25, 3.20 (2s, 12H, 4OCH3), 1.28,
JH6’a,H6’b =10.9, JH6’a,H5’ =2.5 Hz,
J
1.18 (2s, 12H, 4CH3).
Di(3,4,6-tri-O-acetyl-2-azido-2-deoxy-d-galactopyranosyl)-a,a-(1!1:1!
6)-2,3:4,5-di-O-(2’,3’-dimethoxy-butane-2’,3’-diyl)-d-chiro-inositol
(35):
Prepared by reaction of acceptor 7 with donor 21. [a]2D0 = ꢀ33.6 (c=0.3,
CHCl3); 1H NMR (500 MHz, CDCl3): d=5.32 (dd, 2H,
JH4’,H3’ =3.2,
JH4’,H5’ =1.2 Hz, 2H4’), 5.23 (dd, 2H, JH3’,H2’ =10.9, JH3’,H4’ =3.2 Hz, 2H3’),
4.86 (d, 2H, JH1’,H2’ =3.5 Hz, 2H1’), 4.81 (ddd, 2H, JH5’,H6’a =7.6, JH5’,H6’b
=
6.1, JH5’,H4’ =1.2 Hz, 2H5’), 4.09 (dd, 2H, JH6’a,H6’b =11, JH6’a,H5’ =7.6 Hz,
2H6’a), 4.01 (dd, 2H, JH6’b,H6’a =11, JH6’b,H5’ =6.1 Hz, 2H6’b), 3.98–3.89 (m,
4H, H1, H3, H4, H6), 3.87 (dd, 2H, JH2’,H3’ =10.9, JH2’,H1’ =6.5 Hz, 2H2’),
3.82 (brd, 2H, J=2.0 Hz, H2, H5), 3.27, 3.20 (2s, 12H, 4OCH3), 2.14,
2.04, 2.00 (3s, 9H, 3CH3CO), 1.28, 1.19 (2s, 12H, 4CH3); 13C NMR
(125 MHz, CDCl3): d=170.3, 170.1, 169.5 (6CH3CO); 99.9, 98.6 (4C,
BDA), 96.4 (2C1’), 73.4, 69.5, 67.5, 67.1, 66.5, 66.1 (C1, C2, C3, C4, C5, C6,
2C3’, 2C4’, 2C5’), 61.1 (2C6’), 57.9 (2C2’), 48.2, 47.4 (4OCH3), 20.7
(6CH3CO), 17.6, 17.4 (4CH3); MALDI-TOF: m/z: calcd for
C42H62N6O24Na: 1058.0; found: 1057.5 [M+Na]+; calcd for
C42H62N6O24K: 1074.1; found: 1073.8 [M+K]+.
2-Azido-3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranosyl-a-(1!1)-2,5-di-O-
benzyl-3,4-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-l-chiro-inositol (25a), 2-
azido-3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranosyl-b-(1!1)-2,5-di-O-
benzyl-3,4-O-(2’,3’-dimethoxy-butane-2’,3’-diyl)-l-chiro-inositol (25b) and
(%) for C45H59O14N3+3= H2O: C 60.52, H 6.99, N 4.70; found: C 60.40, H
2
6.95, N 4.38.
Chem. Eur. J. 2005, 11, 928 – 938
www.chemeurj.org
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
935

M. B. Cid, M. Martꢀn-Lomas, and F. Alfonso
Compound 32b: [a]D
=
+64.3 (c=0.6, CHCl3); 1H NMR (500 MHz,
2-Azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-d-glucopyranosyl-a-(1!
1)-2,5-di-O-benzyl-3,4-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-d-chiro-inosi-
tol (40a), 2-azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-d-glucopyrano-
syl-b-(1!1)-2,5-di-O-benzyl-3,4-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-d-
chiro-inositol (40b): The pseudodisaccharides were prepared from 14
(50 mg, 0.094 mmol) and 6 (30 mg, 0.063 mmol) as described for the prep-
aration of 16a and 16b, adding TMSOTf (0.03 equiv, 18.9 mL of a solution
0.1m) at ꢀ258C in CH2Cl2 (2 mL) and stirring the reaction mixture for
1 h at ꢀ258C, yielding after flash chromatography (hexane/ethyl acetate
4:1), 40a (12 mg, 22%) and 40b (3 mg, 6%). 40a: [a]D = +58.5 (c=0.6,
CHCl3); 1H NMR (500 MHz, CDCl3): d=7.40–7.20 (m, 20H, 4Bn), 5.45
(s, 1H, CHPh), 4.94–4.65 (4 AB syst, 8H), 4.78 (d, 1H, J=3.7 Hz, H1’),
4.17 (m, 1H, H5’), 4.06 (t, 1H, J=3.1 Hz, H6), 4.06–4.02 (m, 3H, H1, H3,
H4), 3.95 (t, 1H, J=9.4 Hz, H3’), 3.92 (dd, 1H, J=9.3, 2.6 Hz, H5), 3.87
(dd, 1H, J=9.5, 2.7 Hz, H2), 3.70 (dd, 1H, J=10.0, 5.0 Hz, H6’a), 3.60 (t,
1H, J=9.4 Hz, H4’), 3.45 (m, 2H, H2’, H6’b), 3.32 (2s, 6H, 2OCH3), 2.52
(s, 1H, C6OH), 1.38, 1.33 (2s, 6H, 2CH3); 13C NMR (125 MHz, CDCl3):
d=139.3 (C), 138.8 (C), 138.2 (C), 137.8 (C), 129.2–126.3 (20CH, Bn),
101.6 (CHPh), 99.7, 99.6 (2C, BDA), 99.0 (C1’), 83.1 (C1), 78.4 (CH), 76.6
(CH), 75.2 (CH2), 75.1 (CH), 74.4 (CH2), 74.3 (2CH2), 70.6 (CH), 70.3
(CH), 69.9 (2CH), 69.4 (CH), 63.7 (CH), 48.2 (OCH3), 48.1 (OCH3), 18.2
(2CH3); elemental analysis calcd (%) for C46H53O12N3: C 65.80, H 6.35,
N 5.00; found: C 65.53, H 6.29, N 4.53.
CDCl3): d=7.40–7.10 (m, 15H, 3Bn), 4.85–4.52 (3AB syst, 6H), 4.29 (d,
1H, J=7.5 Hz, H1’), 4.08 (brt, 1H, H1), 4.06–4.02 (m, 2H, H6, H5), 3.96–
3.92 (m, 3H, H2, H3, H4), 3.77 (dd, 1H, J=11.1, 2.2 Hz, H6’a), 3.72 (dd,
1H, J=11.0, 3.7 Hz, H6’b), 3.68 (t, 1H, J=9.0 Hz, H3’), 3.46–3.39 (m, 2H,
H2’, H4’), 3.36 (m, 1H, H5’), 3.25–3.21 (3s, 9H, 3OCH3), 3.17 (s, 3H,
3OCH3), 2.50 (s, 1H, OH), 1.30, 1.29, 1.25, 1.18 (4s, 12H, 4CH3);
13C NMR (125 MHz, CDCl3): d=138.6, 138.3, 138.3 (3C, Bn), 128.7–
127.9 (15CH, Bn), 101.4, 100.5, 100.2, 99.3 (4C, BDA), 98.9 (C1’H), 83.9
(CH), 78.0 (CH2), 77.5 (C1H), 77.1 (CH2), 75.9 (CH), 75.6 (CH), 75.2
(CH), 74.2 (CH2), 69.7 (CH), 68.6 (CH2), 68.5 (CH), 67.7 (CH), 66.9
(CH), 66.5 (CH), 48.4, 48.2, 48.1, 47.9 (4C, 2OCH3), 18.2, 18.1, 18.1, 18.0
(4CH3); elemental analysis calcd (%) for C45H59O14N3+3H2O: C 58.74,
H 7.12, N 4.56; found: C 58.60, H 7.24, N 4.85.
Compound 33: 1H NMR (500 MHz, CDCl3): d=7.40–7.10 (m, 30H,
6Bn), 4.80–4.12 (6AB syst, 12H), 4.35 (d, 2H, J=7.8 Hz, 2H1’), 4.03 (dd,
2H, J=7.8, 3.2 Hz), 3.97 (m, 2H), 3.80–3.69 (m, 6H), 3.47–3.12 (m, 8H),
3.22 (s, 6H, 2OCH3), 3.18 (s, 6H, 2OCH3), 1.25 (s, 6H, 2CH3), 1.20 (s,
6H, 2CH3); elemental analysis calcd (%) for C72H86O18N6: C 65.34, H
6.55, N 6.35; found: C 65.31, H 6.57, N 6.25.
3,4,6-Tri-O-acetyl-2-azido-2-deoxy-d-galactopyranosyl-a(1!1)-2,5-di-O-
benzyl-3,4-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-l-chiro-inositol (29): This
pseudodisaccharide was prepared from 21 (46 mg, 0.096 mmol) and 10
(23 mg, 0.048 mmol) as described for the preparation of 16a and 16b,
adding TMSOTf (0.1 equiv, 0.96 mL of a solution 0.05m) at ꢀ258C in
CH2Cl2 (1 mL) and stirring the reaction mixture for 1 h, yielding after
flash chromatography (hexane/ethyl acetate 4:1) 28a (14 mg, 37%) and
Compound 40b: [a]D
=
+10.0 (c=0.1, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.40–7.20 (m, 20H, 4Bn), 5.52 (s, 1H, CHPh), 5.01–4.61
(4AB syst, 8H), 4.59 (d, 1H, J=8.0 Hz, H1’), 4.26 (dd, 1H, J=10.4,
4.9 Hz, H6’a), 4.18 (t, 1H, J=10.1 Hz, H3), 4.12 (brs, 1H, H1), 4.10 (brs,
1H, H6), 4.02 (t, 1H, J=10.1 Hz, H4), 3.90 (dd, 1H, J=10.1, 3.1 Hz, H2),
3.80 (dd, 1H, J=10.0, 3.2 Hz, H5), 3.71 (t, 1H, J=10.4 Hz, H6’b), 3.61 (t,
1H, J=9.3 Hz, H4’), 3.45 (t, 1H, J=9.3 Hz, H3’), 3.31–3.24 (m, 8H, H2’,
H5’, 2OCH3), 2.52 (s, 1H, C6OH), 1.38, 1.33 (2s, 6H, 2CH3); 13C NMR
(125 MHz, CDCl3): d=139.8 (C), 138.9 (C), 138.2 (C), 137.4 (C), 129.4–
126.3 (20CH, Bn), 103.7 (C1’), 101.6 (CHPh), 99.8, 99.6 (2C, BDA), 81.8,
79.3, 78.2, 76.9, 76.3, 75.4, 75.3, 74.1, 74.0, 70.1, 70.4, 68.9, 66.8, 66.3
(10CH, 4CH2), 48.2, 48.1 (2OCH3), 18.2 (2CH3); elemental analysis
calcd (%) for C46H53O12N3: C 65.80, H 6.35, N 5.00; found: C 65.71, H
6.43, N 4.77.
the unreacted acceptor 10 (14 mg, 61%). 29: [a]D
= +24.3 (c=0.7,
CHCl3); 1H NMR (500 MHz, CDCl3): d=7.40–7.20 (m, 10H, 2Bn), 5.48
(d, 1H, J=3.8 Hz, H1’), 5.34 (brd, 1H, J=3.0 Hz, H4’), 5.00 (dd, 1H, J=
11.2, 3.1 Hz, H3’), 4.95–4.64 (2 AB syst, 4H), 4.23 (t, 1H, J=10.1 Hz, H3),
4.16 (brt, 1H, J=3.1 Hz, H1), 4.02–3.96 (m, 3H, 2H6’, H4), 3.88 (dd, 1H,
J=10.1, 3.0 Hz, H2), 3.79 (m, 1H, H5’), 3.74–3.68 (m, 3H, H2’, H5 and
H6), 3.28, 3.25 (2s, 6H, 2OCH3), 2.48 (s, 1H, C6OH), 2.10, 2.08, 2.06 (3s,
9H, 3CH3CO), 1.37, 1.35 (2s, 6H, 2CH3); 13C NMR (75 MHz, CDCl3):
d=170.7, 170.4, 170.1 (3CH3CO), 139.4, 138.7 (2C, Bn), 128.8–127.4
(10CH, Bn), 99.8, 99.6 (2C, BDA), 98.5 (C1’), 77.0 (CH), 76.3 (CH), 75.3
(C1), 74.5, 74.4 (2CH2), 71.3 (CH), 70.2 (CH), 69.9 (CH), 68.7 (CH), 67.7
(CH), 67.0 (CH), 62.1 (CH2), 58.0 (CH), 48.1, 47.9 (2OCH3), 21.0, 21.0,
20.9 (3CH3CO), 18.2 (2CH3); MALDI-TOF: m/z: calcd for C38H49
N3O15+Na: 810.8; found: 811.0 [M+Na]+; calcd for C38H49N3O15+K+:
826.9; found: 828.0 [M+K]+; elemental analysis calcd (%) for
C38H49O15N3+2H2O: C 55.40, H 6.40, N 5.10; found: C 55.54, H 6.10, N
5.43.
2-Azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-d-glucopyranosyl-a-(1!
1)-2,5-di-O-benzyl-3,4-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-l-chiro-inosi-
tol (41): The pseudodisaccharide was prepared from 14 (30 mg,
0.056 mmol) and 10 (18 mg, 0.038 mmol) as described for the preparation
of 16a and 16b, adding TMSOTf (0.03 equiv, 5.2 mL of a solution 0.22m)
at ꢀ258C in CH2Cl2 (1 mL) and stirring the reaction mixture for 1 h at
ꢀ258C, yielding after flash chromatography (hexane/ethyl acetate 4:1) 41
(18 mg, 56%) and unreacted acceptor 14 (8 mg, 42%). 41: [a]D = ꢀ30.7
(c=0.6, CHCl3); 1H NMR (500 MHz, CDCl3): d=7.50–7.20 (m, 20H,
4Bn), 5.56 (s, 1H, CHPh), 5.43 (d, 1H, J=4.0 Hz, H1’), 4.97–4.62 (4AB
syst, 8H), 4.31 (t, 1H, J=10.1 Hz, H3), 4.22 (m, 1H, H6’a), 4.20 (t, 1H,
J=3.0 Hz, H1), 4.02 (t, 1H, J=9.9 Hz, H4), 3.91 (dd, 1H, J=10.2, 2.9 Hz,
H2), 3.89 (t, 1H, J=3.4 Hz, H6), 3.85 (t, 1H, J=9.4 Hz, H3’), 3.78 (dd,
1H, J=9.9, 3.4 Hz, H5), 3.73–3.64 (m, 3H, H5’, H6’b, H4’), 3.41 (dd, 1H,
J=9.4, 4.0 Hz, H2’), 3.33, 3.32 (2s, 6H, 2OCH3), 2.52 (s, 1H, C6OH),
1.38, 1.33 (2s, 6H, 2CH3); 13C NMR (125 MHz, CDCl3): d=139.5 (C),
138.6 (C), 138.3 (C), 137.5 (C), 129.3–126.2 (20CH, Bn), 101.5 (CHPh),
99.8, 99.6 (2C, BDA), 99.0 (C1’), 82.9 (CH), 77.5 (CH), 76.6 (2CH), 75.5
(CH2), 75.1 (C1H), 74.4 (CH2), 74.3 (CH2), 71.2 (CH), 70.4 (CH), 69.8
(CH), 69.1 (CH2), 63.7 (CH), 63.4 (CH), 48.0 (2OCH3), 18.2 (2CH3); ele-
mental analysis calcd (%) for C46H53O12N3: C 65.80, H 6.35, N 5.00;
found: C 65.40, H 6.44, N 4.54.
3,4,6-Tri-O-acetyl-2-azido-2-deoxy-d-galactopyranosyl-a-(1!1)-2,3:4,5-
di-O-(2’,3’-dimethoxybutane-2’,3’-diyl)-l-chiro-inositol (36): The pseudo-
disaccharide was prepared from 21 (40 mg, 0.084 mmol) and 11 (18 mg,
0.042 mmol) as described for the preparation of 16a and 16b, adding
TMSOTf (0.1 equiv, 0.84 mL of a solution 0.05m) at ꢀ258C in CH2Cl2
(1 mL) and stirring the reaction mixture for 1 h, yielding after flash chro-
matography (hexane/ethyl acetate 2:1) 36 (21 mg, 69%) and the unreact-
ed acceptor 11 (5 mg, 30%). 36: [a]D
= +78.3 (c=1.0, CHCl3);
1H NMR (500 MHz, CDCl3): d=5.63 (d, 1H, J=3.7 Hz, H1’), 5.40 (d,
1H, J=3.0 Hz, H4’), 5.07 (dd, 1H, J=11.3, 3.1 Hz, H3’), 4.15–4.09 (m, 4H,
H5’, H6’a, H3, H1), 4.03 (m, 1H, H6’b), 3.97 (dd, 1H, J=9.9, 2.7 Hz, H2),
3.92 (t, 1H, J=9.9 Hz, H4), 3.87 (brt, 1H, J=3.1 Hz, H6), 3.82 (dd, 1H,
J=10.1, 3.1 Hz, H5), 3.72 (dd, 1H, J=11.2, 3.7 Hz, H2’), 3.25, 3.24, 3.22,
3.22 (4s, 12H, 4OCH3), 2.12, 2.04, 2.00 (3s, 9H, 3CH3CO), 1.29, 1.27,
1.24, 1.21 (4s, 12H, 4CH3); 13C NMR (75 MHz, CDCl3): d=170.1, 170.4,
170.2 (3CH3CO), 100.6, 100.2, 99.3, 98.9 (4C, BDA), 98.0 (C1’H), 73.5
(C1H), 70.9 (CH), 69.5 (CH), 68.9 (CH), 68.1 (CH), 67.8 (CH), 67.2
(CH), 66.5 (CH), 66.4 (CH), 62.1 (CH2), 58.3 (CH), 48.4, 48.3, 48.2, 48.1
(4OCH3), 21.0, 21.0, 20.9 (3CH3CO), 18.1, 18.0, 17.9, 17.8 (4CH3);
MALDI-TOF: m/z: calcd for C30H47N3O17Na: 744.7; found: 745.6
[M+Na]+; calcd for C30H47N3O17K: 760.8; found: 762.6 [M+K]+; elemen-
tal analysis calcd (%) for C30H47O17N3: C 49.92, H 6.56, N 5.82; found: C
50.05, H 6.84, N 5.60.
trans-4-tert-Butylcyclohexyl-2-azido-2-deoxy-3,4,6-tri-O-benzyl-a-d-glu-
copyranoside (45a) and trans-4-tert-butylcyclohexyl-2-azido-2-deoxy-
3,4,6-tri-O-benzyl-b-d-glucopyranoside (45b): A) From trichloroacetimi-
date 13 prepared as the pure a isomer (95 mg, 0.153 mmol) and trans-4-
tert-butylcyclohexanol (42) (20 mg, 0.13 mmol) as described for the prep-
aration of 16a and 16b, adding TMSOTf (0.1 equiv, 130 mL of a solution
0.1m) at ꢀ258C in CH2Cl2 (2 mL) and stirring the reaction mixture for
1 h at ꢀ258C, yielding after flash chromatography (hexane/ethyl acetate
4:1) 45a (10 mg, 12%) and 45b (42 mg, 52%).
936
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Chem. Eur. J. 2005, 11, 928 – 938

Glycosylation Reactions
FULL PAPER
B) From trichloroacetimidate 44, prepared as the pure b isomer, using
the experimental procedure described above 45a (14 mg, 17%) and 45b
(41 mg, 51%) were obtained.
ꢀ258C, yielding after flash chromatography (hexane/ethyl acetate 4:1)
47a (33 mg, 48%) and 47b (12 mg, 17%). 47a: [a]D
= +52.6 (c=0.6,
CHCl3); 1H NMR (500 MHz, CDCl3): d=7.50–7.20 (m, 10H, 2Bn), 5.56
(s, 1H, CHPh), 5.01 (d, 1H, J=3.5 Hz, H1’), 4.90 (AB syst, 2H), 4.25 (dd,
1H, J=10.3, 4.9 Hz, H6’b), 4.10 (t, 1H, J=9.3 Hz, H3’), 4.00 (m, 1H, H5’),
3.73 (t, 1H, J=10.4 Hz, H6’a), 3.68 (t, 1H, J=9.3 Hz, H4’), 3.50 (m, 1H,
H1), 3.26 (dd, 1H, J=9.3 and 3.5 Hz, H2’), 2.10 (m, 2H), 1.80 (brs, 2H),
1.40–1.20 (m, 3H), 1.00 (m, 2H), 0.80 (s, 9H, 3CH3); 13C NMR
(125 MHz, CDCl3): d=138.3 (C), 137.6 (C), 129.3–126.3 (10CH, Bn),
101.7 (CH), 97.4 (CH), 83.3 (CH), 78.4 (CH), 76.3 (CH), 75.3 (CH2), 69.3
(CH2), 63.2 (CH), 63.1 (CH), 47.5 (CH), 34.2 (CH2), 32.6 (CH2), 30.0 (C),
27.9 (3CH3), 25.9 (CH2), 25.8 (CH2); elemental analysis calcd (%) for
C30H39O5N3: C 69.07, H 7.53, N 8.05; found: C 68.88, H 7.58, N 8.34.
Compound 45a: [a]D
=
+77.1 (c=0.5, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.40–7.20 (m, 15H, 3Bn), 5.06 (d, 1H, J=3.6 Hz, H1’), 4.89–
4.46 (3AB syst, 6H), 4.00 (t, 1H, J=9.3 Hz, H3’), 3.91 (m, 1H, H5’), 3.76
(dd, 1H, J=11.0, 3.8 Hz, H6’a), 3.68 (t, 1H, J=9.3 Hz, H4’), 3.64 (dd, 1H,
J=11.0, 2.0 Hz, H6’b), 3.48 (m, 1H, H1), 3.26 (dd, 1H, J=9.3, 3.6 Hz, H2’),
2.10 (m, 1H), 2.00 (m,1H), 1.80 (m, 2H), 1.40–1.20 (m, 2H), 1.00 (m,
3H), 0.80 (s, 9H, 3CH3); 13C NMR (125 MHz, CDCl3): d=138.4 (C),
138.3 (C), 138.2 (C), 129.8–128.0 (15CH, Bn), 96.6 (CH), 80.4 (CH), 78.8
(CH), 77.9 (CH), 75.6 (CH2), 75.4 (CH2), 73.8 (CH2), 70.9 (CH), 68.7
(CH2), 63.5 (CH), 47.5 (CH), 34.1 (CH2), 32.6 (C), 32.3 (CH2), 27.9
(3CH3), 26.0 (CH2), 25.8 (CH2); elemental analysis calcd (%) for
C37H47O5N3: C 72.40, H 7.71, N 6.84; found: C 72.13, H 7.70, N 6.62.
Compound 47b: [a]D
=
ꢀ62.5 (c=0.6, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.50–7.20 (m, 10H, 2Bn), 5.50 (s, 1H, CHPh), 4.80 (AB syst,
2H), 4.50 (d, 1H, J=7.9 Hz, H1’), 4.32 (dd, 1H, J=10.8, 5.3 Hz, H6’b),
3.78 (t, 1H, J=10.3 Hz, H6’a), 3.67 (t, 1H, J=9.3 Hz, H4’), 3.60–3.53 (m,
1H, H1), 3.49 (t, 1H, J=9.2 Hz, H3’), 3.42 (t, 1H, J=9.1 Hz, H2’), 3.36
(m, 1H, H5’), 2.10 (m, 2H), 1.80 (m, 2H), 1.40–1.20 (m, 3H), 1.00 (m,
2H), 0.80 (s, 9H, 3CH3). 13C NMR (125 MHz, CDCl3): d=138.3 (C),
137.5 (C), 129.3–126.3 (10CH, Bn), 101.6 (CH), 101.4 (CH), 81.8 (CH),
79.9 (CH), 79.3 (CH), 75.2 (CH2), 69.0 (CH2), 66.6 (CH), 66.5 (CH), 47.4
(CH), 34.2 (CH2), 32.6 (CH2), 30.0 (C), 27.9 (3CH3), 25.9 (CH2), 25.8
(CH2); elemental analysis calcd (%) for C30H39O5N3: C 69.07, H 7.53, N
8.05; found: C 68.73, H 7.28, N 7.95.
Compound 45b: [a]D
=
ꢀ3.0 (c=1.6, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.40–7.20 (m, 15H, 3Bn), 4.89–4.52 (3AB syst, 6H), 4.38 (d,
1H, J=7.5 Hz, H1’), 3.72 (dd, 1H, J=11.0, 1.8 Hz, H6’a), 3.65 (dd, 1H, J=
11.0, 5.1 Hz, H6’b), 3.61–3.52 (m, 3H, H4’, H3’, H1), 3.42–3.36 (m, 2H, H5’,
H2’), 2.10 (brs, 2H), 1.80 (m, 2H), 1.30 (m, 2H), 1.00 (m, 3H), 0.80 (s,
9H, 3CH3); 13C NMR (125 MHz, CDCl3): d=138.5 (C), 138.4 (C), 138.3
(C), 128.8–127.9 (15CH, Bn), 101.0 (CH), 83.55 (CH), 79.7 (CH), 78.2
(CH), 75.8 (CH2), 75.4 (CH2), 75.3 (CH), 73.8 (CH2), 69.2 (CH2), 66.6
(CH), 47.5 (CH), 34.3 (CH2), 32.7 (CH2), 32.6 (C), 27.9 (3CH3), 26.0
(CH2), 25.8 (CH2); elemental analysis calcd (%) for C37H47O5N3: C 72.40,
H 7.71, N 6.84; found: C 72.58, H 7.83, N 6.50.
cis-4-tert-Butylcyclohexyl 2-azido-2-deoxy-3-O-benzyl-4,6-benzylidene-a-
d-glucopyranoside (48a) cis-4-tert-butylcyclohexyl 2-azido-2-deoxy-3-O-
benzyl-4,6-O-benzylidene-b-d-glucopyranoside (48b): The compounds
were prepared from 14 (81 mg, 0.153 mmol) and cis-4-tert-butylcyclohexa-
nol (43) (20 mg, 0.13 mmol) as described for the preparation of 16a and
16b, adding (0.1 equiv, 130 mL of a solution 0.1m) of TMSOTf at ꢀ258C
in CH2Cl2 (2 mL) and stirring the reaction mixture for 1 h at ꢀ258C,
yielding after flash chromatography (hexane/ethyl acetate 4:1) 48a
cis-4-tert-Butylcyclohexyl-2-azido-2-deoxy-3,4,6-tri-O-benzyl-a-d-gluco-
pyranoside (46a), cis-4-tert-butylcyclohexyl-2-azido-2-deoxy-3,4,6-tri-O-
benzyl-b-d-glucopyranoside (46b): A) From trichloroacetimidate 13 pre-
pared as the pure a isomer (95 mg, 0.153 mmol) and cis-4-tert-butylcyclo-
hexanol (43) (20 mg, 0.13 mmol) as described for the preparation of 16a
and 16b, adding TMSOTf (0.1 equiv, 130 mL of a solution 0.1m) at ꢀ258C
in CH2Cl2 (2 mL) and stirring the reaction mixture for 1 h at ꢀ258C,
yielding after flash chromatography (hexane/ethyl acetate 4:1) 46a
(10 mg, 12%) and 46b (30 mg, 37%).
(33 mg, 48%) and 48b (15 mg, 22%). 48a: [a]D
= +68.8 (c=0.6,
CHCl3); 1H NMR (500 MHz, CDCl3): d=7.50–7.20 (m, 10H, 2Bn), 5.60
(s, 1H, CHPh), 4.97 (d, 1H, J=3.8 Hz, H1’), 4.90 (AB syst, 2H), 4.27 (dd,
1H, J=10.1, 4.7 Hz, H6’b), 4.15 (t, 1H, J=9.5 Hz, H3’), 3.95 (m, 1H, H5’),
3.90 (m, 1H, H1), 3.77–3.70 (m, 2H, H6’a, H4’), 3.25 (dd, 1H, J=9.6,
3.8 Hz, H2’), 2.00–1.90 (m, 2H), 1.60–1.30 (m, 6H), 1.00 (m, 1H), 0.80 (s,
9H, 3CH3); 13C NMR (125 MHz, CDCl3): d=138.3 (C), 137.5 (C), 129.3–
126.3 (10CH, Bn), 101.7 (CH), 97.0 (CH), 83.5 (CH), 75.7 (CH), 75.3
(CH2), 72.2 (CH), 69.3 (CH2), 63.2 (2CH), 48.2 (CH), 33.0 (CH2), 32.5
(C), 29.6 (CH2), 27.9 (3CH3), 22.0 (CH2), 21.6 (CH2); elemental analysis
calcd (%) for C30H39O5N3: C 69.07, H 7.53, N 8.05; found: C 68.84, H
7.39, N 7.84.
B) From trichloroacetimidate 44, prepared as the pure b isomer, follow-
ing the same experimental procedure described above to yield 46a
(11 mg, 13%) and 46b (34 mg, 42%).
Compound 46a: [a]D
=
+85.0 (c=0.4, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.40–7.20 (m, 15H, 3Bn), 5.00 (d, 1H, J=3.6 Hz, H1’), 4.89–
4.46 (3 AB syst, 6H), 4.05 (dd, 1H, J=10.3, 9.0 Hz, H3’), 3.91–3.85 (m,
2H, H5’ and H1), 3.76 (dd, 1H, J=11.0, 3.6 Hz, H6’a), 3.71 (t, 1H, J=
9.0 Hz, H4’), 3.63 (dd, 1H, J=10.6, 2.0 Hz, H6’b), 3.22 (dd, 1H, J=10.2,
3.6 Hz, H2’), 2.00 (m, 1H), 1.90 (m, 1H), 1.60–1.30 (m, 6H), 1.00 (m,
1H), 0.80 (s, 9H, 3CH3); 13C NMR (125 MHz, CDCl3): d=138.4 (C),
138.3 (C), 138.2 (C), 128.8–128.1 (15CH, Bn), 96.3 (CH), 79.9 (CH), 78.9
(CH), 75.5 (CH2), 75.4 (CH2), 73.9 (CH2), 71.8 (CH), 71.1 (CH), 68.7
(CH2), 63.6 (CH), 48.3 (CH), 32.9 (CH2), 32.4 (CH2), 30.0 (C), 27.8
(3CH3), 22.1 (CH2), 21.7 (CH2); elemental analysis calcd (%) for
C37H47O5N3: C 72.40, H 7.71, N 6.84; found: C 72.48, H 7.73, N 6.70.
Compound 48b: [a]D
=
ꢀ80.6 (c=0.7, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.50–7.20 (m, 10H, 2Bn), 5.50 (s, 1H, CHPh), 4.85 (AB syst,
2H), 4.40 (d, 1H, J=7.9 Hz, H1’), 4.32 (dd, 1H, J=10.3, 4.9 Hz, H6’b),
4.00 (brs, 1H, H1), 3.78 (t, 1H, J=10.3 Hz, H6’a), 3.69 (t, 1H, J=8.7 Hz,
H4’), 3.48 (t, 1H, J=8.7 Hz, H3’), 3.42 (dd, 1H, J=8.7, 7.9 Hz, H2’), 3.45
(m, 1H, H5’), 2.00 (m, 2H), 1.50 (m, 2H), 1.47–1.33 (m, 4H), 1.00 (m,
1H) and 0.80 (s, 9H, 3CH3); 13C NMR (125 MHz, CDCl3): d=138.4 (C),
137.5 (C), 129.3–126.3 (6CH), 101.6 (CH), 100.7 (CH), 81.9 (CH), 79.3
(CH), 75.2 (CH2), 73.6 (CH), 69.0 (CH2), 67.3 (CH), 66.5 (CH), 48.2
(CH), 32.6 (CH2), 30.0 (C), 29.9 (CH2), 27.8 (3CH3), 21.8 (CH2), 21.5
(CH2); elemental analysis calcd (%) for C30H39O5N3: C 69.07, H 7.53, N
8.05; found: C 69.17, H 7.67, N 8.13.
Compound 46b: [a]D
=
ꢀ13.8 (c=1.3, CHCl3); 1H NMR (500 MHz,
CDCl3): d=7.40–7.20 (m, 15H, 3Bn), 4.89–4.52 (3 AB syst, 6H), 4.31 (d,
1H, J=7.7 Hz, H1’), 4.02 (brs, 1H, H1), 3.69 (dd, 1H, J=11.0, 2.0 Hz,
H6’b), 3.64 (dd, 1H, J=11.0, 4.7 Hz, H6’a), 3.58 (t, 1H, J=9.2 Hz, H4’),
3.43–3.35 (m, 3H, H2’, H3’, H5’), 2.02 (brs, 2H), 1.58–1.32 (m, 6H), 1.00
(m, 1H), 0.85 (s, 9H, 3CH3); 13C NMR (125 MHz, CDCl3): d=138.5
(2C), 138.3 (C), 128.8–127.9 (15CH, Bn), 100.2 (CH), 83.5 (CH), 78.2
(CH), 75.8 (CH2), 75.4 (CH2), 75.3 (CH), 73.8 (CH2), 73.2 (CH), 69.1
(CH2), 67.3 (CH), 48.3 (CH), 32.9 (CH2), 32.6 (C), 30.0 (CH2), 27.8
(3CH3), 21.8 (CH2), 21.6 (CH2); elemental analysis calcd (%) for
C37H47O5N3: C 72.40, H 7.71, N 6.84; found: C 72.38, H 7.61, N 6.72.
Acknowledgement
trans-4-tert-Butylcyclohexyl-2-azido-2-deoxy-3-O-benzyl-4,6-benzylidene-
a-d-glucopyranoside (47a) and trans-4-tert-butylcyclohexyl-2-azido-2-
deoxy-3-O-benzyl-4,6-O-benzylidene-b-d-glucopyranoside (47b): The
compounds were prepared from 14 (81 mg, 0.153 mmol) and trans-4-tert-
butylcyclohexanol (20 mg, 0.13 mmol) 42 as described for the preparation
of 16a and 16b, adding (0.1 equiv, 130 mL of a solution 0.1m) of TMSOTf
at ꢀ258C in CH2Cl2 (2 mL) and stirring the reaction mixture for 1 h at
We thank the Direcciꢂn General de Investigaciꢂn for financial support
(Grant BQU 2002-03734) and the Ministry of Science and Technology
for a Ramꢂn y Cajal contract (to M.B.C.).
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Received: July 20, 2004
Published online: December 9, 2004
938
ꢄ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2005, 11, 928 – 938