Acylation of carbohydrates over Al2O3: Preparation of partially and fully acylated carbohydrate derivatives and acetylated glycosyl chlorides

Article abstract of DOI:10.1016/j.carres.2005.11.035

Selective and per-O-acylation of carbohydrate derivatives using acyl chlorides and Al₂O₃, a solid support reagent, is reported. This protocol does not require the addition of any base or activator. This methodology has been further extended to the selective acylation of carbohydrate diols and the one-pot preparation of acetylated glycosyl chlorides direct from free reducing sugars. The yields obtained in most of the cases are excellent.

Full text of DOI:10.1016/j.carres.2005.11.035

Carbohydrate
RESEARCH
Carbohydrate Research 341 (2006) 339–350
Acylation of carbohydrates over Al2O3: preparation of partially
and fully acylated carbohydrate derivatives and acetylated
glycosyl chloridesI
Pallavi Tiwari and Anup Kumar Misra*
Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226 001, UP, India
Received 5 October 2005; received in revised form 11 November 2005; accepted 18 November 2005
Available online 20 December 2005
Abstract—Selective and per-O-acylation of carbohydrate derivatives using acyl chlorides and Al2O3, a solid support reagent, is
reported. This protocol does not require the addition of any base or activator. This methodology has been further extended to
the selective acylation of carbohydrate diols and the one-pot preparation of acetylated glycosyl chlorides direct from free reducing
sugars. The yields obtained in most of the cases are excellent.
Ó 2005 Elsevier Ltd. All rights reserved.
Keywords: Carbohydrates; Acylation; Al2O3; Regioselectivity; Chemoselectivity
Acylation of hydroxyl groups of carbohydrates is one
of the most commonly used functional group protection
techniques in the synthesis of oligosaccharides. Per-O-
acetylated sugars are inexpensive and useful intermedi-
ates for the synthesis of naturally occurring glycosides,
oligosaccharides, and other glycoconjugates.1–7 The acet-
ylation reaction has also been employed for structural
elucidation of many natural products containing carbo-
hydrates. The most commonly used acyl protecting
groups used in the carbohydrate syntheses are acetyl,
benzoyl, chloroacetyl, and pivaloyl, which are prepared
by using acetyl chloride, acetic anhydride, benzoyl chlo-
ride, chloroacetyl chloride, pivaloyl chloride, respec-
tively, in the presence of a base.8 Acetylation of sugar
alcohols is often carried out using a large excess of acetic
anhydride with pyridine serving as the solvent and base,
despite its toxicity and unpleasant odor.9,10 Sometimes,
pyridine derivatives such as 4-(N,N-dimethylamino)pyri-
dine and 4-(pyrrolidino)pyridine are added as a cocata-
lyst to speed up the acylation.11,12 A variety of other
catalysts in combination with excess acetic anhydride
and solvent have been employed in the acetylation of car-
bohydrate derivatives, including sodium acetate,13 sulfu-
ric acid,14 perchloric acid,15 and a number of Lewis acid
catalysts such as, iodine,16 Sc(OTf)3,17 Cu(OTf)2,18
CoCl2,19 ZnCl2,20 BiOCl–SOCl2,21 LiClO4,22 FeCl3,23
BiCl3,24 and a series of heterogeneous catalysts such as,
montmorillonite K-10,25 zeolites,26 nafion-H.27 Recently,
29
a ZnCl2–sodium acetate combination28 or InCl3 with
acetic anhydride under microwave condition has been
reported for the acetylation of carbohydrates. A few
reports have also appeared on the acetylation of
carbohydrates using ionic liquids as solvents and cata-
lysts.30,31 In most cases, acetic anhydride is used in excess,
which sometimes causes troublesome workup during the
neutralization process and thereby makes the protocol
tedious. Despite the number of available methods, there
is a need to develop a fast clean reaction protocol for
the acetylation of sugars particularly over solid surfaces,
which reduces conventional workup and purification
procedures. In this context, we recently reported a fast
per-O-acetylation of carbohydrates using HClO4–SiO2
as a solid catalyst and stoichiometric quantity of acetic
anhydride to minimize workup.32 While applying this
methodology for the acetylation of carbohydrate deriva-
tives containing acid labile functional groups such as,
q CDRI Communication No. 6775.
*
Corresponding author. Tel.: +91 522262411; fax: +91 5222623405;
e-mail: akmisra69@rediffmail.com
0008-6215/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2005.11.035

340
P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
benzylidene acetals, isopropylidene acetals, and triphen-
ylmethyl (trityl) groups, it was observed that some acid
labile functional groups were cleaved during the reaction.
To overcome this unwanted side reaction, we have been
interested in developing economical methods for a gen-
eral acylation of carbohydrate derivatives, that avoids
the use of an acid or a base, such as pyridine or its deriv-
atives, in addition to a reaction protocol that would be
easy to perform for scaling up without the requirement
of workup or tedious chromatographic purifications.
Reactions on solid supports are always welcome because
of the possibility of recycling the solid support and the
exclusion of conventional workup procedures. Recently,
a few reports33–35 appeared involving the use of Al2O3 as
a solid support for the acylation of alcohols, phenols,
amine, thiols, which have excluded the addition of a base
or acid as catalyst. Prompted by this work, we envisioned
that acylation of carbohydrate derivatives containing
acid labile functional groups could be best performed
over basic Al2O3 as a solid support using a minimum
quantity of the acylating agents. Although previously
Al2O3 has been used in carbohydrate chemistry to pro-
mote transesterification of sugar alcohols with ethyl acet-
ate, the yields were poor and the reaction required long
reaction times and a large amount of Al2O3.36–38 We dis-
close here an efficient and economical method for the
selective and complete acylation of carbohydrate deriva-
tives and those with acid-susceptible functional groups
using acyl chlorides and basic Al2O3 as a solid support
in a solvent or under solvent-free conditions.
To evaluate the potential of basic Al2O3 in acetylating
carbohydrate derivatives, a series of preliminary experi-
ments were carried out using a variable quantity of acetyl
chloride and basic Al2O3 with CH3CN as the solvent
(Scheme 1). It was observed that use of 1.2 M equiv of
acetyl chloride and 2.0 equiv of basic Al2O3 per hydroxyl
group in CH3CN produced an excellent yield of per-O-
acetylated carbohydrate derivatives, even those contain-
ing acid labile functionalities. Increasing the quantity of
acetyl chloride and Al2O3 did not increase the yield or re-
duce the reaction time significantly; rather it reduced the
selectivity of the acylation between two hydroxyl groups.
With the satisfactory yields with acetyl chloride, the same
reaction was done using acetic anhydride as acetylating
agent. However, the reaction did not proceed well and
even after 48 h only ꢀ30% of the product was obtained.
The same reaction was performed without addition of
CH3CN, but the reaction time was only reduced by a
few minutes and the yield was comparable. Using the
similar molar ratio of the substrates and reagents, a series
of other acyl chlorides (chloroacetyl chloride, pivaloyl
chloride, benzoyl chloride) were allowed to react with
carbohydrate derivatives containing acid labile func-
tional groups in the presence of basic Al2O3. In every
case, excellent yields of the corresponding acylated prod-
ucts were isolated (Tables 1 and 2). It was observed that
acid chlorides react more efficiently than the correspond-
ing acid anhydride and that benzoyl chloride reacts much
more slowly than acetyl or chloroacetyl chlorides. Many
acid labile functional groups such as benzylidene acetals,
isopropylidene acetals, TBDMS ethers are stable under
these reaction conditions.
The methodology has also been applied to the selec-
tive acylation of carbohydrate derivatives. The primary
hydroxyl groups of the carbohydrate derivatives were
acylated very efficiently, while leaving the secondary hy-
droxyl groups unacylated. The slow reactivity of benzo-
yl chloride as found earlier provided the possibility of
selective benzoylation of primary alcohols in the pres-
ence of secondary alcohols. In earlier reports, selective
benzoylation of primary alcohols over secondary alco-
hols of carbohydrate derivatives has been carried out
using benzoyl chloride and pyridine at low tempera-
ture39 through the use of highly toxic benzoyl cyanide40
or through stannylidene acetal derivatives.41 In our
hands, selective acetylations of primary alcohol of car-
bohydrate derivatives were also achieved by using a lim-
ited quantity of acetyl chloride under controlled reaction
conditions. Thus, selective acetylation of primary alco-
hols of the carbohydrate diols has been achieved by
using 1.2 M equiv acetyl chloride and 2.0 M equiv basic
Al2O3 from 0 to 10 °C. In the case of pivaloylations, no
secondary alcohol protected products were observed,
even after prolonged reaction times (Table 3). It is worth
noting that among the solvents most frequently used for
acylation reactions, for example, dichloromethane,
CH3CN, dichloroethane, THF, that CH3CN was the
most effective, producing both high product yields and
cleaner reactions (Table 4).
HO
HO
HO
RO
RO
RO
After selective and complete acylation of a wide range
of partially protected carbohydrate derivatives, the
methodology was extended to the acylation of unpro-
tected reducing sugars. Thus, a series of unprotected sug-
ars were reacted with acetyl chloride (1.2 equiv per OH
group) and benzoyl chloride (1.5 equiv per OH group)
over basic Al2O3 (2.0 equiv per OH group) either in
CH3CN or under solvent-free conditions. In the case of
acetylation, complete reaction was observed in a few
hours. While the formation of the per-O-acetylated sugar
derivatives, a faster moving spot on TLC was also
RCOCl/Al2O3
CH3CN
O
O
OR
OH
OH
OR
O
Ph
O
Ph
RCOCl/Al2O3
CH3CN
O
O
O
HO
O
RO
OH
OR
OMe
OMe
R = Acetyl, chloroacetyl, pivaloyl, benzoyl
Scheme 1.

P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
341
Table 1. Per-O-acylation of carbohydrate derivatives over basic Al2O3 (2.0 equiv per OH) as a solid support at room temperature
Entry
Substrate (1)
% Yield of per-O-acylated product (time in h)
AcCla (2)
BzClb (3)
CAClb (4)
Ac2Oc
OH
98 (1.0)48
[99]d
90 (2.5)
[92]d
HO
O
a
—
30 (48.0)
20 (48.0)
—
HO
OH
OCH3
HO
HO
OH
O
b
c
95 (1.0)
[98]d
—
—
—
CH3
OH
O
OH
96 (1.0)49
[95]d
92 (2.5)
O
HO
HO
SC2H5
OH
OH
O
HO
HO
d
e
94 (0.5)50
—
—
—
—
—
OAllyl
NPhth
OH
O
98 (0.5)51
[98]d
40 (48.0)
HO
HO
SPh
NPhth
SPh
95 (0.5)52
—
—
—
Me
O
f
OH
OH
HO
HO
HO
OH
O
g
98 (1.0)18
—
—
—
—
—
SC6H4(4-CH3)
OH
HO
HO
OAc
O
h
—
88 (0.5)
SC2H5
OAc
AcCl: Acetyl chloride; BzCl: benzoyl chloride; CACl: chloroacetyl chloride; Ac2O: acetic anhydride. The numbered superscripts correspond to
literature references of the products.
a 1.2 equiv per OH.
b 1.5 equiv per OH.
c 2.0 equiv per OH.
d Yields obtained under solvent-free conditions.
noticed, whose formation increased with time. After some
experimentation, it was confirmed that the faster moving
compounds were per-O-acetylated glycopyranosyl chlo-
rides. To isolate the acetylated glycosyl chlorides, similar
acetylation reactions were carried out using an excess of
acetyl chloride (2.5 equiv per OH group) and the reaction
times were extended to allow for complete conversion of
initially formed per-O-acetylated sugars to the acetylated
sugar chlorides. Acetylated glycosyl chlorides are impor-
tant intermediates in oligosaccharide syntheses, as well
as in the generation of anomeric carbocations and radi-
cals. Although, the preparation of acetylated glycosyl
chlorides has been reported earlier, most have used
per-O-acetylated glycopyranoses as the starting materi-
als.21,24,42–47 Using the present protocol, the preparation
of acetylated glycosyl chlorides can be achieved directly
from unprotected sugars. The results of acetylation and
conversion to the glycosyl chlorides using a series of
unprotected sugars are presented in Table 5. The same
protocol was applied to the case of benzoylation of free
sugars using benzoyl chloride over basic Al2O3 and it
took significantly longer for the reaction to furnish per-
O-benzoylated sugars. Further addition of benzoyl chlo-
ride or longer reaction time did not produce benzoylated
glycosyl chlorides. It was observed that the time required
for acylation of unprotected sugars was much more than
the partially protected carbohydrate derivatives. To
extend this protocol, D-glucose was treated with acetyl

342
P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
Table 2. Per-O-acylation of carbohydrate derivatives containing acid labile functional groups over basic Al2O3 (2.0 equiv per OH) as a solid support
at room temperature
Entry
Substrate (5)
% Yield of per-O-acylated product (time in min)
AcCla (6)
BzClb (7)
CAClb (8)
Ac2Oc
O
NH
a
98 (30)
—
—
—
N
O
TBDMSO
O
HO
OH
OH
HO
HO
CH(SEt)2
b
c
96 (60)
[95]d
—
—
30 (48.0)
HO
OH
O
OH
O
O
98 (20)22
[98]d
95 (45)
90 (20)
—
O
O
Ph
O
O
O
d
e
92 (40)
95 (40)
92 (90)
90 (90)
—
—
—
—
SPh
HO
OH
Ph
O
O
O
HO
SPh
O
OH
Ph
Ph
O
f
96 (40)53
[95]d
92 (90)
—
—
—
O
OMe
HO
OH
O
O
O
g
98 (25)
98 (20)
90 (45)
20 (48.0)
SPh
HO
NPhth
HO
HO
OH
O
h
i
—
—
—
O
O
O
OH
O
O
98 (30)
98 (45)
96 (20)
30 (48.0)
O
O
Ph
O
O
O
j
—
—
88 (60)
—
—
—
—
OMe
AcO
OH
OTBDPS
O
HO
HO
k
90 (120)
SC2H5
OH
O
OH
O
OH
O
l
92 (90)
—
—
—
O
O
SPh
HO
HO
OH
AcCl: Acetyl chloride; BzCl: benzoyl chloride; CACl: chloroacetyl chloride; Ac2O: acetic anhydride. The numbered superscripts correspond to
literature references of the products.
a 1.2 equiv per OH.
b 1.5 equiv per OH.
c 2.0 equiv per OH.
d Yields obtained under solvent-free conditions.

P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
343
Table 3. Selective acylation of carbohydrate diols over basic Al2O3 (2.0 M equiv) using acyl chloridesa
Entry
Sugar diol (9)
HO
Product (10)
Time (h)
4.0
Acyl chloride (equiv)
Benzoyl chloride (1.5)
Yield (%)
HO
BnO
OH
OBz
O
O
a
92
BnO
BnO
BnO
OCH3
OCH3
HO
BzO
HO
BzO
OH
O
OAc
O
b
c
1.5
2.0
Acetyl chloride (1.2)
Acetyl chloride (1.2)
90
90
BzO
BzO
OCH3
O
OCH3
O
HO
HO
BzO
HO
HO
BzO
SPh
SPh
OBz
OBz
HO
HO
AcO
BzO
HO
AcO
O
O
d
e
4.0
4.5
Benzoyl chloride (1.5)
Benzoyl chloride (1.5)
85
92
AcO
AcO
OCH3
OCH3
BzO
HO
OBn
OBn
O
O
HO
HO
O
O
O
O
PivO
HO
HO
HO
OBn
O
OBn
O
f
8.0
Pivaloyl chloride (1.2)
Acetyl chloride (1.2)
Benzoyl chloride (1.5)
Acetyl chloride (1.2)
88
95
92
65
O
O
O
O
HO
HO
AcO
AcO
HO
AcO
O
O
g
h
i
1.0
SPh
SPh
NPhth
NPhth
HO
HO
AcO
BzO
HO
AcO
O
O
2.0
SPh
SPh
NPhth
NPhth
Ph
Ph
O
O
O
O
45 minb
O
O
OMe
OMe
HO
AcO
OH
OH
a Reaction conditions: Sugar diol (1.0 mmol), basic Al2O3 (2.0 mmol), and acyl chloride (1.2 mmol) in CH3CN (5.0 mL) was stirred at 5–10 °C.
b Reaction carried out at 0 °C; a small amount of 2-O-acetylated product (ꢀ20%) was also isolated.
Table 4. Comparison of solvents in the acetylation of carbohydrates using acetyl chloride over Al2O3 as a solid support
Entry
Substrate
Product
Solvent
Time (h)
Yield (%)
CH3CN
THF
CH2Cl2
1.0
2.5
5.0
5.0
98
95
85
90
HO
HO
HO
AcO
AcO
AcO
O
O
1
OCH3
OCH3
OH
OAc
ClCH2CH2Cl
O
O
OH
OAc
O
O
CH3CN
THF
CH2Cl2
0.5
1.5
1.0
1.0
98
92
95
95
O
O
2
O
O
O
O
ClCH2CH2Cl

344
P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
Table 5. Acylation of unprotected carbohydrates over basic Al2O3 (2.0 equiv per OH group) using acyl chloridesa
Entry
a
Sugars (11)
Products (12)
Time (h) Acyl chloride (equiv) Yield (%)b a/bc Ref.
HO
AcO
O
O
HO
AcO
1.5
5
Acetyl chloride (6.0)
97
5.9:1 18
HO
AcO
OAc
OH
OH
OH
OH
OAc
AcO
AcO
AcO
HO
O
O
HO
b
c
Acetyl chloride (12.5) 90
a
a
24
—
HO
AcO
OH
Cl
Br
AcO
AcO
AcO
HO
O
O
HO
4
Acetyl bromide
20
HO
AcO
OH
HO
BzO
BzO
BzO
O
O
HO
d
e
12
Benzoyl chloride (7.5) 92
a
54
HO
OBz
OH
OH
OBz
HO
OH
O
HO
AcO
OAc
O
1.5
4.5
Acetyl chloride (6.0)
95
6.2:1 18
AcO
OAc
OAc
HO
OH
AcO
AcO
OAc
O
HO
OH
O
HO
f
Acetyl chloride (12.5) 87
Benzoyl chloride (7.5) 92
a
24
AcO
HO
OH
OH
Cl
HO
OH
O
HO
BzO
BzO
OBz
O
g
12
3.4:1 54
OBz
HO
OBz
OH
O
OAc
O
HO
HO
HO
AcO
AcO
AcO
h
i
1.5
4.5
Acetyl chloride (6.0)
92
4:1
18
24
OH
OH
OH
OAc
OAc
O
OH
O
AcO
AcO
HO
HO
HO
Acetyl chloride (12.5) 85
Benzoyl chloride (7.5) 95
a
AcO
Cl
OBz
O
OH
O
BzO
BzO
BzO
HO
HO
HO
j
10
2.2:1 54
OBz
OH
OAc
H3C
HO
H3C
AcO
O
O
k
l
2
1
1
Acetyl chloride (6.0)
Acetyl chloride (4.8)
Acetyl chloride (4.8)
85
92
90
a
18
H2O
OH
OAc
OH
OAc
O
O
HO
AcO
AcO
HO
4.5:1 55
10:1 30
OH
OAc
OH
OH
OAc
OAc
HO
HO
AcO
O
O
AcO
m
HO
AcO
NHAc
NHAc
AcO
AcO
AcO
HO
O
O
HO
n
2.5
Acetyl chloride (10.0) 86
a
56
HO
OH
AcNH
NHAc
Cl

P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
345
Table 5 (continued)
Entry
Sugars (11)
Products (12)
Time (h) Acyl chloride (equiv) Yield (%)b a/bc Ref.
HO
HO
HO
AcO
O
O
AcO
AcO
o
1.5
2.5
Acetyl chloride (4.8)
92
1:1.3 57
OH
OH
OAc
NPhth
O
PhthN
O
AcO
AcO
AcO
HO
HO
HO
p
q
Acetyl chloride (10.0) 85
1:1
58
59
PhthN
NPhth
Cl
CO2CH3
CO2CH3
O
O
HO
HO
AcO
AcO
2
Acetyl chloride (4.8)
90
b
OH
OAc
OAc
OH
AcO
AcO
HO
HO
OAc
O
OH
O
AcO
HO
O
O
O
O
AcO
AcO
HO
HO
r
1.5
Acetyl chloride (20.0) 92
—
32
HO
HO
AcO
5H2O
AcO
O
O
O
HO
AcO
AcO
O
OH
OAc
OH
OAc
HO
HO
HO
AcO
AcO
OAc
O
O
OH
HO
AcO
HO
HO
O
AcO
AcO
O
H2O
s
1.5
Acetyl chloride (15.0) 95
—
32
O
O
O
O
O
HO
AcO
OH
OAc
O
HO
AcO
OH
OAc
a All reactions were carried out at room temperature.
b Isolated yield.
c a/b ratio was determined from the 1H NMR spectra of the inseparable mixture.
bromide in the presence of Al2O3 in an identical molar
ratio of reagents as used in the case of acetyl chloride.
As expected, acetobromoglucose was formed; however,
the isolated product was mostly the corresponding hemi-
acetal because of the instability of acetobromoglucose
compared to acetochloroglucose. In both the case of
acetylation and benzoylation, formation of per-O-acyl-
ated furanosyl glycoses was not observed, which was
confirmed from the NMR spectra of the products. From
the above-mentioned observations it is evident that
though the use of this one-pot reaction protocol that
per-O-acylated sugar derivatives and acetylated glycosyl
chlorides can be prepared efficiently directly from unpro-
tected reducing sugars by controlling the acylating agents
and reaction time.
a longer reaction time for completion; (2) require prior
preparation of the catalyst; (3) use hazardous chemicals
as an activator; or (4) cannot be used with acid labile
functional groups. From the comparison in Table 6, it
is clear that the present protocol has significant advan-
tages over previously reported methods. Although in
some cases, the yield is comparable to the earlier reports
(e.g., use of iodine or HClO4–SiO2), the most notable
advantage is that it can acylate carbohydrate derivatives
containing acid labile functional groups very efficiently
without any side reactions.
In conclusion, a simple, efficient, and economical
protocol for the acylation of carbohydrates has been
devised using Al2O3, which avoids the use of any acid
or base as an activator. This methodology has been
further extended to the selective acylation of carbo-
hydrate derivatives and also the one-pot preparation
of acetylated glycosyl chlorides directly from free sugars.
In most of the cases, yields were good to excellent. This
To further prove the efficacy of this method, a com-
parison study with previously reported methods for
acylation of carbohydrates was carried out (Table 6).
Most of the previously reported protocols either (1) take

346
P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
Table 6. Comparative study of acetylation using different reported catalysts
Substrate
Reagent (equiv)
Catalyst
Time (min)
Yield (%)
Ref.
Ac2O (5.0)
Ac2O (4.0)
Ac2O (2.2)
Ac2O (3.0)
Ac2O (2.2)
Ac2O (3.0)
AcCl (2.4)
Pyridine (excess)
I2
Cu(OTf)2
60.0
30.0
300.0
2.0
20.0
12.0 h
40.0
95
9 and 10
16
18
29a
30 (with degraded product)
90
20 (with degraded product)
10 (with degraded product)
20 (reaction not completed)
92
Ph
O
O
InCl3
O
SPh
HClO4–SiO2
Al2O3 (2.0 equiv)
Al2O3 (2.0 equiv)
32
33
HO
OH
This workb
Ac2O (2.5)
Ac2O (2.0)
Ac2O (1.1)
Ac2O (1.5)
Ac2O (1.2)
Ac2O (1.5)
AcCl (1.2)
Pyridine (excess)
I2
Cu(OTf)2
InCl3
HClO4–SiO2
Al2O3
Al2O3
45
20
300
2.0
30.0
12.0 h
20
95
9 and 10
16
18
29a
OH
O
40 (with degraded product)
80
35 (with degraded product)
No desired product isolated
30 (reaction not completed)
98
O
O
O
O
32
33
This workb
a Microwave irradiation.
b Reaction conditions: Diol (1.0 mmol), basic Al2O3 (2.0 mmol), and acyl chloride in CH3CN (5.0 mL) was stirred at room temperature.
method is operationally simple and does not require any
aqueous workup, which therefore reduces purification of
the products. Along with these features, this method
may be considered as an attractive alternative to the
existing methodologies for the acylation of carbohy-
drates particularly those containing acid-susceptible
functionalities.
ane–EtOAc 2:1), the reaction mixture was filtered
through Celite and evaporated followed by coevapora-
tion twice with toluene under reduced pressure.
Although in most of the cases, considerably pure prod-
ucts were obtained, analytical samples were prepared by
passing the reaction product through a column over
SiO2 using hexane–EtOAc as the eluant.
1.3. General procedure for complete acylation of partially
protected carbohydrate derivatives under solvent-free
conditions
1. Experimental
1.1. General
The molar ratio of substrate and reagents were exactly
as mentioned above for the complete acylation proce-
dure, except the reaction was performed without using
any solvent. After completion of the reaction, the mix-
ture was diluted with CH2Cl2 and filtered through Celite
and the filtrate was removed under reduced pressure to
furnish the product.
All reactions were monitored by thin-layer chromato-
graphy using silica gel coated TLC plates. Spots on
TLC were visualized by warming ceric sulfate (2%
CeSO4 in 2 N H2SO4) sprayed plates in hot plate at
ꢀ150 °C. Silica gel 100–200 mesh (SRL, India) was used
for column chromatography. ESI-MS mass spectra were
1
recorded on Micromass Quattro II. H and 13C NMR
was recorded on Bruker Advance DPX 200 MHz using
TMS as the internal reference. Chemical shift values are
expressed in d parts per million. Elemental analysis was
carried out on Carlo ERBA-1108 analyzer. Optical rota-
tions were measured at 25 °C on a Rudolf Autopol III
polarimeter. Commercially available grades of organic
solvents of adequate purity were used in reactions.
1.4. General procedure for selective acylation of partially
protected carbohydrate derivatives
An acid chloride (acetyl chloride (1.20 mmol), benzoyl
chloride (1.50 mmol), pivaloyl chloride (1.2 mmol))
was added to a stirred solution of carbohydrate deriva-
tive (1.0 mmol) and basic Al2O3 (204.0 mg, 2.0 mmol) in
CH3CN (5.0 mL) at 15–20 °C. After allowing the mix-
ture to stir for appropriate time (Table 3), the mixture
was filtered through Celite and the filtrate was removed
to furnish selectively acylated product.
1.2. General procedure for complete acylation of partially
protected carbohydrate derivatives
To a stirred suspension of the sugar alcohol (1.0 mmol)
and basic Al2O3 (204.0 mg, 2.0 mmol) in distilled
CH3CN (5.0 mL) was added acid chloride (1.20 mmol;
in the case of benzoyl chloride 1.5 mmol) in one portion
at rt and the reaction mixture was allowed to stir for
appropriate time as mentioned in Tables 1 and 2. After
completion of the reaction as monitored by TLC (hex-
1.5. General procedure for complete acylation of unpro-
tected reducing sugars
To a suspension of carbohydrate (1.0 mmol) and basic
Al2O3 (2.0 equiv per OH) in CH3CN (5.0 mL) was
added an acid chloride (acetyl chloride (1.2 equiv per

P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
347
OH), benzoyl chloride (1.5 equiv per OH)) in one por-
tion and the reaction mixture was allowed to stir at rt
for appropriate time (Table 5). After completion of the
reaction, the mixture was diluted with CH2Cl2 and fil-
tered through Celite. The filtrate was evaporated to fur-
nish per-O-acylated carbohydrate derivatives.
2.7 Hz, 1H), 5.28 (dd, J = 7.5, 4.2 Hz, 1H), 5.06 (m,
1H), 4.27 (dd, J = 16.8, 3.0 Hz, 1H), 4.13 (dd,
J = 17.0, 4.8 Hz, 1H), 4.07 (d, J = 4.2 Hz, 1H, H-1),
2.80–2.72 (m, 2H), 2.62–2.54 (m, 2H), 2.14, 2.09, 2.08,
2.06, 2.05 (5s, 15H, 5COCH3), 1.31 (t, J = 7.2 Hz, 3H,
CH2CH3), 1.22 (t, J = 7.2 Hz, 3H, CH2CH3); 13C
NMR (CDCl3): d 170.7, 170.5, 170.2 (2C), 169.9, 72.5,
70.4, 68.8 (2C), 61.8, 51.2, 25.9, 25.3, 21.0 (2C), 20.9
(3C), 14.8, 14.6; ESI-MS (M+Na): 519; Anal. Calcd
for C20H32O10S2: C, 48.37; H, 6.50. Found: C, 48.20;
H, 6.75.
1.6. General procedure for the one-pot preparation of
acetylated glycosyl chlorides from unprotected reducing
sugars
To a suspension of carbohydrate (1.0 mmol) and basic
Al2O3 (2.0 equiv per OH) in CH3CN (5.0 mL) was
added acetyl chloride (2.5 equiv per OH) in one portion
and the reaction mixture was allowed to stir at rt for the
appropriate time (Table 5). After completion of the
reaction, the mixture was diluted with CH2Cl2 and fil-
tered through a Celite. The filtrate was evaporated to
furnish the acylated glycosyl chloride.
1.7.4. Phenyl 2,3-di-O-acetyl-4,6-O-benzylidene-1-thio-
b-D-glucopyranoside (6d). White solid; mp 119 °C;
[a]D ꢂ2.1 (c 1.2, CHCl3); IR (Neat): 2956, 2893, 1748,
1586, 1481, 1439, 1373, 1225, 1089, 1041, 912, 744,
686. 1H NMR (CDCl3): d 7.46–7.25 (m, 10H, aromatic),
5.49 (s, 1H, PhCH), 5.33 (dd, J = 8.9, 9.1 Hz, 1H, H-2),
5.04–4.96 (dd, J = 9.8, 8.9 Hz, 1H, H-3), 4.80 (d,
J = 9.9 Hz, 1H, H-1), 4.39 (m, 1H, H-5), 3.79 (dd,
J = 10.0, 9.4 Hz, 1H, H-40), 3.71–3.56 (m, 2H, H-6ab),
2.10, 2.03 (2s, 6H, 2COCH3); ESI-MS (M+Na): 467;
Anal. Calcd for C23H24O7S: C, 62.15; H, 5.44. Found:
C, 61.94; H, 5.60.
1.7. Spectral data for new compounds
1.7.1. 5,6,7,9-Tetra-O-acetyl-4,8-anhydro-1,3-dideoxy-D-
glycero-L-gluco-nonulose (2b). White solid; mp 91–
25
92 °C; ½aꢁD +5.6 (c 1.5, CHCl3); IR (KBr): 2941, 2884,
1746, 1704, 1383, 1227, 1097, 1038, 908 cmꢂ1
;
1H
1.7.5. Phenyl 2,3-di-O-acetyl-4,6-O-benzylidene-1-thio-
b-D-galactopyranoside (6e). Oil; [a]D ꢂ19 (c 1.5, CHCl3);
IR (Neat): 2887, 1734, 1630, 1586, 1441, 1403, 1375,
1295, 1250, 1225, 1180, 1092, 1052, 999, 933, 745,
NMR: d 5.34 (br s, 1H, H-7), 5.01–4.98 (m, 2H, H-5
and H-6), 4.05–3.98 (m, 2H, H-9a,b), 3.96–3.85 (m, 2H,
H-4, H-8), 2.81–2.68 (dd, J = 16.3, 8.5 Hz, 1H, H-3a),
2.50–2.40 (dd, J = 16.4, 3.4 Hz, 1H, H-3b), 2.16, 2.15,
2.02, 2.01, 1.96 (5s, 15H, 5COCH3); 13C NMR (CDCl3):
d 204.5, 169.9 (2C), 169.7, 169.6, 74.4, 74.3, 71.9, 69.3,
67.9, 61.6, 45.6, 30.9, 20.7, 20.6 (2C), 20.5; ESI-MS
(M+Na): 411; Anal. Calcd for C17H24O10: C, 52.57;
H, 6.23. Found: C, 52.48; H, 6.30.
1
697 cmꢂ1; H NMR (CDCl3): d 7.62–7.25 (m, 10H, aro-
matic), 5.46 (s, 1H, PhCH), 5.34 (t, J = 9.8 Hz, 1H, H-2),
5.00 (dd, J = 9.9, 3.4 Hz, 1H, H-3), 4.69 (d, J = 9.7 Hz,
1H, H-1), 4.36 (m, 2H, H-4, H-6a), 4.00 (dd, J = 12.4,
1.4 Hz, 1H, H-6b), 3.59–3.56 (m, 1H, H-5), 2.08, 2.02
(2s, 6H, 2COCH3); ESI-MS (M+Na): 467; Anal. Calcd
for C23H24O7S: C, 62.15; H, 5.44. Found: C, 61.90; H,
5.65.
1.7.2. 2,3-Di-O-acetyl-5-O-tert-butyldimethylsilyl uridine
(6a). White solid; mp 83.5 °C; [a]D ꢂ2.6 (c 1.5,
CHCl3); IR (KBr): 3202, 3072, 2929, 2858, 1749, 1715,
1460, 1380, 1241, 1125, 1101, 1046, 834, 813, 778,
1.7.6. Phenyl 3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-
phthalimido-1-thio-b-D-glucopyranoside
(6g). White
1
757 cmꢂ1; H NMR (CDCl3): d 10.18 (br s, 1H, NH),
solid; mp 115 °C; [a]D +18 (c 1.2, CHCl3); IR (KBr):
7.72 (d, J = 9.0 Hz, 1H), 6.15 (d, J = 6.0 Hz, 1H), 5.62
(d, J = 9.0 Hz, 1H), 5.20–5.18 (m, 2H), 4.09 (br s, 1H),
3.85–3.73 (m, 2H), 2.04, 1.98 (2s, 6H, 2COCH3), 0.85
(s, 9H, C(CH3)3), 0.06 (s, 6H, 2CH3Si); 13C NMR
(CDCl3): d 169.3, 169.0, 163.0, 150.6, 139.0, 103.0,
85.0, 83.4, 73.1, 71.4, 63.0, 25.7 (2C), 25.4, 20.4, 20.1,
18.1, ꢂ5.8 (2C); ESI-MS (M+Na): 465; Anal. Calcd
for C19H30N2O8Si: C, 51.57; H, 6.83. Found: C, 51.31;
H, 7.02.
2934, 2829, 2367, 1715, 1595, 1366, 1228, 1105, 1030,
1
966, 719 cmꢂ1; H NMR (CDCl3): d 7.85–7.71 (m, 4H,
aromatic), 7.42–7.25 (m, 10H, aromatic), 5.84 (dd,
J = 9.5, 9.0 Hz, 1H, H-3), 5.80 (d, J = 10.6 Hz, 1H, H-
1), 5.50 (s, 1H, PhCH), 4.41 (d, J = 5.9 Hz, 1H, H-4),
4.30 (dd, J = 10.2, 10.1 Hz, 1H, H-2), 3.82–3.70 (m,
3H, H-5 and H-6ab), 1.87 (s, 3H, COCH3); 13C NMR
(CDCl3): d 17.5, 168.2, 167.6, 137.3–124.1 (aromatic),
102.1, 84.3, 79.4, 70.9, 69.0, 54.7, 20.9; ESI-MS
(M+Na): 554; Anal. Calcd for C29H25NO7S: C, 65.52;
H, 4.74. Found: C, 65.70; H, 4.96.
1.7.3. 2,3,4,5,6-Penta-O-acetyl-D-glucose diethyl dithio-
acetal (6b). White solid; mp 47 °C; [a]D +13.2 (c
1.5, CHCl3); IR (KBr): 2971, 2932, 1752, 1432, 1372,
1.7.7. 3,5,6-Tri-O-acetyl-1,2-O-isopropylidene-a-D-gluco-
furanose (6h). White solid; mp 78 °C; [a]D +23.8 (c 1.2,
CHCl3); IR (KBr): 2994, 2364, 1741, 1595, 1378, 1244,
1
1219, 1069, 1033, 967, 758 cmꢂ1; H NMR (CDCl3): d
5.76 (dd, J = 7.5, 2.7 Hz, 1H), 5.43 (dd, J = 8.1,

348
P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
1
1166, 1079, 1026 cmꢂ1; H NMR (CDCl3): d 5.93 (d,
J = 3.5 Hz, 1H), 5.35 (d, J = 2.8 Hz, 1H), 5.27–5.13
(m, 1H), 4.60 (dd, 2.2, 16.3 Hz, 1H), 4.48 (d,
J = 3.6 Hz, 1H), 4.39 (dd, J = 2.0, 14.0 Hz, 1H), 4.17–
4.03 (m, 1H), 2.06 (s, 6H, 2COCH3), 2.01 (s, 3H,
COCH3), 1.52, 1.32 (2s, 6H, C(CH3)2); ESI-MS
(M+Na): 369; Anal. Calcd for C15H22O9: C, 52.02; H,
6.40. Found: C, 51.83; H, 6.62.
7.99 (m, 2H, aromatic), 7.61–7.40 (m, 3H, aromatic),
5.91 (dd, J = 3.5, 1.7 Hz, 1H), 5.47 (br s, 1H), 4.60
(dd, J = 3.5, 1.1 Hz, 1H), 4.38–4.22 (m, 2H), 4.10–4.01
(m, 2H), 1.55, 1.42, 1.31, 1.26 (4s, 12H, C(CH3)2);
13C NMR (CDCl3): d 165.1, 133.6–128.6 (aromatic),
112.5, 109.6, 105.4, 83.8, 80.3, 76.7, 72.9, 67.6, 27.3,
27.2, 26.7, 25.6; ESI-MS (M+Na): 387; Anal. Calcd
for C19H24O7: C, 62.63; H, 6.64. Found: C, 62.40; H,
6.90.
1.7.8. Phenyl 2,6-di-O-acetyl-3,4-O-isopropylidene-b-D-
galactopyranosyl-(1!4)-2,3,6-tri-O-acetyl-1-thio-b-D-
glucopyranoside (6i). Oil; [a]D +5.4 (c 1.2, CHCl3); IR
(KBr): 2923, 2855, 2363, 1730, 1461, 1218, 769 cmꢂ1. 1H
NMR (CDCl3): d 7.52–7.20 (m, 5H, aromatic), 5.30–
5.16 (dd, J = 10.8, 8.1 Hz, 1H, H-2), 4.92 (t,
J = 9.5 Hz, 1H, H-20), 4.87–4.80 (m, 1H), 4.68 (d,
J = 9.8 Hz, 1H, H-1), 4.53 (d, J = 11.2 Hz, 1H, H-10),
4.35–4.20 (m, 3H), 4.19–4.02 (m, 3H), 3.95–3.90 (m,
1H), 3.80–3.55 (m, 2H), 2.08, 2.04 (2s, 15H, 5COCH3),
1.52, 1.31 (2s, 6H, C(CH3)2); 13C NMR (CDCl3): d
170.5, 170.4, 170.0, 169.4, 169.3, 133.2–128.4 (aromatic),
111.0, 100.6, 85.7, 78.1, 77.2, 76.2, 73.8, 73.4, 72.9, 71.2,
70.6, 63.4, 62.7, 27.7, 26.5, 21.0 (3C), 20.9 (2C); ESI-MS
(M+Na): 707; Anal. Calcd for C31H40O15S: C, 54.38; H,
5.89. Found: C, 54.03; H, 6.10.
1.7.12. Methyl 3-O-acetyl-2-O-benzoyl-4,6-O-benzylidene-
b-D-glucopyranoside (7j). Oil; [a]D ꢂ68 (c 1.2, CHCl3);
IR (Neat): 2937, 1735, 1600, 1459, 1367, 1278,
1
1100, 1020, 990, 716 cmꢂ1; H NMR (CDCl3): d 8.03–
7.99 (m, 2H, aromatic), 7.53–7.27 (m, 8H, aromatic),
5.60 (t, J = 9.4 Hz, 1H, H-2), 5.51 (s, 1H, PhCH),
5.20 (dd, J = 7.8, 9.4 Hz, 1H, H-3), 4.58 (d,
J = 7.8 Hz, 1H, H-1), 4.44–4.36 (dd, J = 4.6, 10.3 Hz,
1H, H-4), 3.84 (t, J = 9.4 Hz, 2H, H-6ab), 3.63 (dd,
J = 4.8, 9.3 Hz, 1H, H-5), 3.53 (s, 3H, CH3), 1.97 (s,
3H, COCH3); 13C NMR (CDCl3): d 169.9, 166.0,
137.2, 133.6, 130.3 (2C), 129.9, 129.4, 128.8 (2C), 128.6
(2C), 126.5 (2C), 102.8, 101.8, 79.2, 72.7, 72.4, 69.0,
66.9, 57.6, 21.1; ESI-MS (M+Na): 451; Anal. Calcd
for C23H24O8: C, 64.48; H, 5.65. Found: C, 64.15; H,
5.82.
1.7.9. Phenyl 2,3-di-O-benzoyl-4,6-O-benzylidene-1-thio-
b-D-glucopyranoside (6j). White solid; mp 211 °C; [a]D
ꢂ43 (c 1.2, CHCl3); IR (KBr): 2930, 1729, 1598, 1453,
1.7.13. Ethyl 2,3,4-tri-O-benzoyl-6-O-tert-butyldiphenyl-
silyl-1-thio-b-D-glucopyranoside (7k). White solid; mp
117 °C; [a]D +18.6 (c 1.5, CHCl3); IR (KBr): 2372,
1352, 1270, 1094, 1025, 995, 706 cmꢂ1
;
1H NMR
(CDCl3): d 7.95–7.89 (m, 4H, aromatic), 7.49–7.25 (m,
16H, aromatic), 5.75 (t, J = 9.3 Hz, 1H, H-2), 5.48 (s,
1H, PhCH), 5.41 (t, J = 9.3 Hz, 1H, H-3), 4.99 (d,
J = 9.9 Hz, 1H, H-1), 4.42 (dd, J = 9.9, 4.5 Hz, 1H, H-
4), 3.88–3.74 (m, 2H, H-6ab), 3.73–3.67 (m, 1H, H-5);
13C NMR (CDCl3): d 165.3, 164.9, 136.7–126.2 (aro-
matic), 101.5, 86.9, 78.6, 73.3, 71.0, 70.9, 68.5; ESI-MS
(M+Na): 591; Anal. Calcd for C33H28O7S: C, 69.70;
H, 4.96. Found: C, 69.45; H, 5.22.
1722, 1596, 1352, 706 cmꢂ1 1H NMR: d 7.97 (d,
;
J = 7.5 Hz, 2H), 7.90–7.84 (m, 4H), 7.74–7.72 (m, 2H),
7.60 (d, J = 7.2 Hz, 2H), 7.56–7.49 (m, 2H), 7.45–7.29
(m, 11H), 7.22–7.18 (m, 2H), 5.84 (dd, J = 9.3, 9.6 Hz,
1H, H-2), 5.70 (dd, J = 9.6, 9.9 Hz, 1H, H-3), 5.57 (t,
J = 9.6 Hz, 1H, H-4), 4.81–4.78 (d, J = 9.9 Hz, 1H, H-
1), 3.87–3.84 (m, 3H, H-5, H-6ab), 2.91–2.76 (dq, 2H,
CH2CH3), 1.34 (t, J = 7.5 Hz, 3H, CH2CH3), 1.08 (s,
9H, C(CH3)3); ESI-MS (M+Na): 797; Anal. Calcd for
C45H46O8SSi: C, 69.74; H, 5.98. Found: C, 69.93; H,
6.25.
1.7.10. Methyl 2,3-di-O-benzoyl-4,6-O-benzylidene-b-D-
glucopyranoside (6k). White solid; mp 187 °C; [a]D
ꢂ10.8 (c 1.2, CHCl3); IR (KBr): 3021, 2929, 2365,
1.7.14. 3-O-Chloroacetyl-1,2:5,6-di-O-isopropylidene-a-D-
glucofuranose (8i). Yellow oil; [a]D ꢂ78.6 (c 1.2, CHCl3);
IR (Neat): 2990, 2930, 1754, 1378, 1256, 1218, 1162, 1077,
1
1715, 1571, 1218, 769, 672 cmꢂ1; H NMR (CDCl3): d
8.12–7.30 (m, 15H, aromatic), 5.47 (s, 1H, PhCH),
5.32 (t, J = 9.3 Hz, 1H, H-2), 4.95 (t, J = 8.0 Hz, 1H,
H-3), 4.48 (d, J = 7.8 Hz, 1H, H-1), 4.36 (dd, J = 10.4,
5.6 Hz, 1H, H-4), 3.77–3.63 (m, 2H, H-6ab), 3.55–3.53
(m, 1H, H-5), 3.49 (s, 3H, CH3); ESI-MS (M+Na):
513; Anal. Calcd for C28H26O8: C, 68.56; H, 5.34.
Found: C, 68.78; H, 5.50.
; d 5.84
1025, 847, 759 cmꢂ1 1H NMR (CDCl3):
(d, J = 3.6 Hz, 1H), 5.28 (d, J = 1.5 Hz, 1H), 4.48
(d, J = 3.6 Hz, 1H), 4.17 (m, 2H), 4.11–4.04 (m, 3H),
3.96 (m, 1H), 1.50, 1.39 (2s, 6H, C(CH3)2), 1.29 (s, 6H,
C(CH3)2); ESI-MS (M+Na): 359; Anal. Calcd
for C14H21ClO7: C, 49.93; H, 6.29. Found: C, 49.75; H,
6.55.
1.7.11. 3-O-Benzoyl-1,2:5,6-di-O-isopropylidene-a-D-gluco-
furanose (7i). White solid; mp 66 °C; [a]D ꢂ60 (c 1.2,
CHCl3); IR (KBr): 2926, 2365, 1724, 1657, 1584, 1437,
1.7.15. Methyl 6-O-benzoyl-2,3-di-O-benzyl-a-D-galacto-
pyranoside (10a). Oil; [a]D +306 (c 1.2, CHCl3); IR
(Neat): 3449, 3018, 2926, 2371, 1720, 1454, 1275, 1218,
1
1352, 1219, 771, 676 cmꢂ1; H NMR (CDCl3): d 8.08–

P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
349
1
1101, 1049, 766, 711 cmꢂ1; H NMR (CDCl3): d 8.06–
1.7.19. 6-O-Benzoyl-3-O-benzyl-1,2-O-isopropylidene-a-
D-glucofuranose (10e). Oil; [a]D +55 (c 1.2, CHCl3);
IR (Neat): 3449, 2925, 2854, 2370, 1721, 1276, 1219,
7.96 (m, 2H, aromatic), 7.54–7.24 (m, 13H, aromatic),
4.81 (dd, J = 11.6, 2.9 Hz, 2H, PhCH2), 4.72 (br s, 1H,
H-1), 4.68–4.62 (dd, J = 1.6, 12.0 Hz, 2H, PhCH2),
4.57–4.46 (m, 2H, H-6ab), 4.00–3.97 (m, 2H, H-2, H-
3), 3.86–3.85 (m, 2H, H-4, OH), 3.46–3.44 (m, 1H, H-
5), 3.36 (s, 3H, OCH3); 13C NMR (CDCl3): d 166.3,
138.7–128.2 (aromatic), 98.8, 77.7, 76.2, 73.8, 73.4,
68.2, 67.9, 64.3, 55.7; ESI-MS (M+Na): 501; Anal.
Calcd for C28H30O7: C, 70.28; H, 6.32. Found: C,
70.03; H, 6.55.
1075, 771 cmꢂ1 1H NMR (CDCl3): d 8.07–8.03 (m,
;
2H, aromatic), 7.56–7.26 (m, 8H, aromatic), 5.97 (br s,
1H, H-1), 4.77–4.55 (m, 5H), 4.48–4.39 (m, 1H), 4.35–
4.24 (m, 2H), 4.20–4.15 (m, 1H), 1.48, 1.32 (2s, 6H,
C(CH3)2); 13C NMR (CDCl3): d 166.9, 137.2, 127.8,
111.7, 105.2, 82.2, 81.6, 79.6, 72.3, 68.0, 67.3, 26.9,
26.4; ESI-MS (M+Na): 437; Anal. Calcd for
C23H26O7: C, 66.65; H, 6.32. Found: C, 66.43; H, 6.55.
1.7.16. Methyl 6-O-acetyl-2,3-di-O-benzoyl-a-D-gluco-
pyranoside (10b). Oil; [a]D +232 (c 1.2, CHCl3); IR
(Neat): 3428, 3021, 2373, 1724, 1217, 1033, 764,
1.7.20. 3-O-Benzyl-1,2-O-isopropylidene-6-O-trimethyl-
acetyl-a-D-glucofuranose (10f). Oil; [a]D ꢂ49 (c 1.2,
CHCl3); IR (Neat): 3470, 2926, 2855, 1722, 1458,
1
670 cmꢂ1; H NMR (CDCl3): d 8.02–7.96 (m, 4H, aro-
1377, 1287, 1218, 1166, 1078, 1027, 763 cmꢂ1 1H
;
matic), 7.55–7.33 (m, 6H, aromatic), 5.74 (t, J = 8.5,
9.6 Hz, 1H, H-2), 5.25 (dd, J = 10.1, 2.5 Hz, 1H, H-3),
5.13 (br s, 1H, H-1), 4.45 (dq, J = 12.1, 3.7 Hz, 2H,
H-6ab), 4.01–3.96 (m, 1H, H-5), 3.80 (t, J = 9.6,
9.1 Hz, 1H, H-4), 3.43 (s, 3H, OCH3), 2.15 (s, 3H,
COCH3); ESI-MS (M+Na): 467; Anal. Calcd for
C23H24O9 (444): C, 62.16; H, 5.44. Found: C, 62.37;
H, 5.68.
NMR (CDCl3): d 7.36–7.25 (m, 5H, aromatic), 5.87–
5.86 (d, J = 3.3 Hz, 1H, H-1), 4.71–4.57 (AB q,
J = 12.0, 11.7 Hz, 2H, PhCH2), 4.54 (d, J = 3.6 Hz,
1H), 4.37 (d, J = 9.9 Hz, 1H), 4.16 (dd, J = 16.2,
4.8 Hz, 2H), 4.09–4.05 (m, 2H); 13C NMR (CDCl3): d
178.9, 137.4–127.8 (aromatic), 111.6, 105.2, 105.0,
82.3, 81.7, 79.4, 72.3, 67.8, 66.6, 27.2 (3C), 26.9, 26.4;
ESI-MS (M+Na): 417; Anal. Calcd for C23H26O7: C,
63.94; H, 7.67. Found: C, 63.70; H, 7.90.
1.7.17. Phenyl 6-O-acetyl-2,3-di-O-benzoyl-1-thio-b-D-
glucopyranoside (10c). Oil; [a]D +93.4 (c 1.2, CHCl3);
IR (Neat): 3427, 3020, 2926, 2855, 2374, 1722, 1656,
1.7.21. Phenyl 3,6-di-O-acetyl-2-deoxy-2-phthalimido-1-
thio-b-D-glucopyranoside (10g). Oil; [a]D +14 (c 1.2,
CHCl3); IR (Neat): 3434, 2922, 2854, 2369, 1720,
1
1525, 1460, 1218, 771, 671 cmꢂ1; H NMR (CDCl3): d
1
7.97–7.90 (m, 4H, aromatic), 7.53–7.48 (m, 4H, aro-
matic), 7.39–7.25 (m, 7H, aromatic), 5.48 (dd, J = 9.0,
8.4 Hz, 1H, H-2), 5.40 (dd, J = 9.6, 9.3 Hz, 1H, H-3),
4.95 (d, J = 9.6 Hz, 1H, H-1), 4.51–4.39 (m, 2H, H-
6ab), 3.84–3.77 (m, 2H, H-4, OH), 3.48–3.47 (m, 1H,
H-5), 2.10 (s, 3H, COCH3); 13C NMR (CDCl3): d
171.3, 167.3, 165.3, 133.5–128.2 (aromatic), 86.0, 78.2,
77.8, 70.1, 69.4, 63.2, 20.8; ESI-MS (M+Na): 545; Anal.
Calcd for C28H26O8S: C, 64.36; H, 5.01. Found: C,
64.12; H, 5.25.
1380, 1222, 1082, 1034, 769 cmꢂ1; H NMR (CDCl3):
d 7.84–7.47 (m, 4H, aromatic), 7.41–7.24 (m, 5H, aro-
matic), 5.73–5.69 (d, J = 10.5 Hz, 1H, H-1), 5.63 (dd,
J = 9.6, 9.3 Hz, 1H, H-3), 4.47–4.37 (m, 2H, H-6ab),
4.21 (dd, J = 10.5, 10.2 Hz, 1H, H-4), 3.77–3.73 (m,
1H, H-5), 3.57 (dd, J = 9.6, 9.3 Hz, 1H, H-2), 2.12,
1.89 (2s, 6H, 2COCH3); ESI-MS (M+Na): 508; Anal.
Calcd for C24H23NO8S: C, 59.35; H, 4.77. Found: C,
59.58; H, 5.00.
1.7.22. Phenyl 3-O-acetyl-6-O-benzoyl-2-deoxy-2-phthal-
imido-1-thio-b-D-glucopyranoside (10h). Oil; [a]D +7.8
(c 1.2, CHCl3); IR (Neat): 3475, 3020, 2926, 1777,
1.7.18. Methyl 2,3-di-O-acetyl-6-O-benzoyl-a-D-gluco-
pyranoside (10d). Oil; [a]D +110 (c 1.2, CHCl3); IR
(Neat): 3486, 3022, 2371, 1724, 1449, 1373, 1277, 1218,
1
1719, 1385, 1276, 1219, 1082, 1042, 766, 717 cmꢂ1; H
1
1054, 762, 714, 669 cmꢂ1; H NMR (CDCl3): d 8.07–
NMR (CDCl3): d 8.05–8.02 (m, 2H, aromatic), 7.83–
7.78 (m, 2H, aromatic), 7.70–7.45 (m, 3H, aromatic),
7.45–7.40 (m, 4H, aromatic), 7.19–7.07 (m, 3H, aro-
matic), 5.86 (d, J = 10.5 Hz, 1H, H-1), 5.73 (dd,
J = 9.6, 9.3 Hz, 1H, H-3), 4.720 (d, J = 11.4 Hz, 1H,
H-6a), 4.59 (d, J = 12.0 Hz, 1H, H-6b), 4.25 (dd,
J = 10.5, 10.2 Hz, 1H, H-4), 3.97–3.95 (m, 1H, H-5),
3.66 (t, J = 9.3 Hz, 1H, H-2), 1.86 (s, 3H, COCH3);
13C NMR (CDCl3): d 171.5, 168.2, 167.3, 166.8,
134.7–123.9 (aromatic), 83.0, 78.5, 74.6, 69.9, 64.2,
54.1, 20.9; ESI-MS (M+Na): 570; Anal. Calcd for
C29H25NO8S: C, 63.61; H, 4.60. Found: C, 63.38; H,
4.85.
8.03 (m, 2H, aromatic), 7.61–7.40 (m, 3H, aromatic),
5.34 (dd, J = 9.6, 9.4 Hz, 1H, H-2), 4.92–4.90 (d,
J = 3.4 Hz, 1H, H-1), 4.88–4.81 (dd, J = 10.0, 3.5 Hz,
1H, H-3), 4.76–4.68 (dd, J = 12.1, 4.3 Hz, 1H, H-6a),
4.56–4.49 (dd, J = 12.0, 1.7 Hz, 1H, H-6b), 3.97–3.92
(m, 1H, H-5), 3.62 (dd, J = 9.4, 9.3 Hz, 1H, H-4), 3.40
(s, 3H, OCH3), 31.6 (br s, 1H, OH), 2.08 (s, 6H,
2COCH3); 13C NMR (CDCl3): d 171.5, 170.5, 167.0,
133.5–128.8 (aromatic), 97.2, 73.2, 71.2, 70.2, 69.7,
63.8, 55.5, 21.2, 21.0; ESI-MS (M+Na): 405; Anal.
Calcd for C18H22O9: C, 56.54; H, 5.80. Found: C,
56.30; H, 6.01.

350
P. Tiwari, A. K. Misra / Carbohydrate Research 341 (2006) 339–350
28. Limousin, C.; Cleophax, J.; Prtit, A.; Loupy, A.; Lukacs,
Acknowledgments
G. J. Carbohydr. Chem. 1997, 16, 327–342.
29. Das, S. K.; Reddy, K. A.; Krovvidi, V. L. N. R.;
Mukkanti, K. Carbohydr. Res. 2005, 340, 1387–1392.
30. Murugesan, S.; Karst, N.; Islam, T.; Wiencek, J. M.;
Linhardt, R. J. Synlett 2003, 1283–1286.
31. Forsyth, S. A.; Macfarlane, D. R.; Thomson, R. J.; von
Itzstein, M. Chem. Commun. 2002, 714–715.
32. Misra, A. K.; Tiwari, P.; Madhusudan, S. K. Carbohydr.
Res. 2005, 340, 325–329.
Instrumentation facilities from SAIF, CDRI are grate-
fully acknowledged. P.T. thanks CSIR, New Delhi, for
providing a Senior Research fellowship. This project
was funded by the Department of Science and Techno-
logy (DST), New Delhi (SR/FTP/CSA-10/2002), India.
33. Yadav, V. K.; Ganesh Babu, K. J. Org. Chem. 2004, 69,
577–580.
References
34. Yadav, V. K.; Ganesh Babu, K.; Mittal, M. Tetrahedron
2001, 57, 7047–7051.
35. Paul, S.; Nanda, P.; Gupta, R.; Loupy, A. Tetrahedron
Lett. 2002, 43, 4261–4265.
36. Posner, G. H.; Okada, S. S.; Babiak, K. A.; Miura, K.;
Rose, R. K. Synthesis 1981, 789–790.
1. Garegg, P. J. Acc. Chem. Res. 1992, 25, 575–580.
2. Ritchie, G. E.; Moffatt, B. E.; Sim, R. B.; Morgan, B. P.;
Dwek, R. A.; Rudd, P. M. Chem. Rev. 2002, 102, 305–320.
3. Bertozzi, C. R.; Kiessling, L. L. Science 2001, 291, 2357–
2364.
37. Posner, G. H.; Oda, M. Tetrahedron Lett. 1981, 22, 5003–
5006.
38. Rana, S. S.; Barlow, J. J.; Matta, K. L. Tetrahedron Lett.
1981, 22, 5007–5010.
4. Dwek, R. A. Chem. Rev. 1996, 96, 683–720.
5. Toshima, K.; Tatsuta, K. Chem. Rev. 1993, 93, 1503–1531.
6. Nicolaou, K. C.; Mitchell, H. J. Angew. Chem., Int. Ed.
2001, 40, 1576–1624.
39. Malysheva, N. N.; Kochetkov, N. K. Carbohydr. Res.
1982, 105, 173–179.
40. Abbas, S. A.; Haines, A. H. Carbohydr. Res. 1975, 39,
358–363.
41. Ogawa, T.; Matsui, M. Carbohydr. Res. 1977, 56, C1–C6.
42. Korytnyk, W.; Mills, J. A. J. Chem. Soc. 1959, 636–649.
43. Chittenden, G. J. F. Carbohydr. Res. 1993, 242, 297–301.
44. Egan, L. P.; Squires, T. G.; Vercellotti, J. R. Carbohydr.
Res. 1970, 14, 263–266.
7. Davis, B. G. Chem. Rev. 2002, 102, 579–601.
8. Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; Wiley: New York, 1999.
9. Hudson, C. S.; Dale, J. K. J. Am. Chem. Soc. 1915, 37,
1264–1270.
10. Yu, B.; Xie, J.; Deng, S.; Hui, Y. J. Am. Chem. Soc. 1999,
121, 12196–12197.
11. Hofle, G.; Steglich, W.; Vorbruggen, H. Angew. Chem.,
Int. Ed. Engl. 1978, 17, 569–583.
45. Ernst, B.; Winkler, T. Tetrahedron Lett. 1989, 30, 3081–
3084.
46. Cicchillo, R. M.; Norris, P. Carbohydr. Res. 2000, 328,
431–434.
47. Kovac, P.; Edgar, K. J. J. Org. Chem. 1992, 57, 2455–
2467.
48. Horton, D.; Lauterbach, J. H. Carbohydr. Res. 1975, 43,
9–33.
49. Vic, G.; Hasting, J. J.; Howarth, O. W.; Crout, D. H. G.
Tetrahedron: Asymmetry 1996, 7, 709–720.
50. Kiso, M.; Anderson, L. Carbohydr. Res. 1985, 136, 309–
324.
51. Choudhury, U. S. Tetrahedron 1996, 52, 12775–12785.
52. Komba, S.; Shiro, I.; Hideharu, K.; Kiso, M.; Haegawa,
A. Bioorg. Med. Chem. 1996, 4, 1833–1848.
53. Roeen, A.; Padron, J. I.; Vazquez, J. T. J. Org. Chem.
2003, 68, 4615–4630.
12. Scriven, E. F. V. Chem. Soc. Rev. 1983, 12, 129–161.
13. Wolfrom, M. L.; Thompson, A. Methods Carbohydr.
Chem. 1963, 2, 211–215.
14. Hyatt, J. A.; Tindall, G. W. Heterocycles 1993, 35, 227–
234.
15. Binch, H.; Stangier, K.; Thiem, J. Carbohydr. Res. 1998,
306, 409–419.
16. Kartha, K. P. R.; Field, R. A. Tetrahedron 1997, 53,
11753–11766.
17. Lee, J.-C.; Tai, C.-A.; Hung, S.-C. Tetrahedron Lett. 2002,
43, 851–865.
18. Tai, A.-A.; Kulkarni, S. S.; Hung, S.-C. J. Org. Chem.
2003, 68, 8719–8722.
19. Ahmad, S.; Iqbal, J. J. Chem. Soc., Chem. Commun. 1987,
114–115.
20. Vogel, A. I. Vogel’s Textbook of Practical Organic
Chemistry, 5th ed.; Wiley: New York, 1989; pp 644–651.
21. Ghosh, R.; Chakraborty, A.; Maiti, S. Tetrahedron Lett.
2004, 45, 9631–9634.
54. DÕAccorso, N. B.; Thiel, I. M. E.; Schuller, M. Carbohydr.
Res. 1983, 124, 177–184.
55. Durette, P. L.; Horton, D. J. Org. Chem. 1971, 36, 2658–
2669.
22. Lu, K.-C.; Hsieh, S.-Y.; Patkar, L. N.; Chen, C.-T.; Lin,
C.-C. Tetrahedron 2004, 60, 8967–8973.
56. Nashed, M. A.; Slife, C. W.; Kiso, M.; Anderson, L.
Carbohydr. Res. 1980, 82, 237–252.
23. Dasgupta, F.; Singh, P. P.; Srivastava, H. C. Carbohydr.
Res. 1980, 80, 346–349.
57. Lemieux, R. U.; Takeda, T.; Chung, B. Y. In Synthetic
Methods for Carbohydrates; El Khadem, H. S., Ed.; ACS
Symposium Series; American Chemical Society, 1976; Vol.
39, pp 90–115.
58. Jansson, K.; Noori, G.; Magnusson, G. J. Org. Chem.
1990, 55, 3181–3185.
24. Montero, J.-L.; Winum, J.-Y.; Leydet, A.; Kamal, M.;
Pavia, A. A.; Roque, J.-P. Carbohydr. Res. 1997, 297, 175–
180.
25. Bhaskar, P. M.; Loganathan, D. Tetrahedron Lett. 1998,
39, 2215–2218.
26. Bhaskar, P. M.; Loganathan, D. Synlett 1999, 129–131.
27. Kumareswaran, R.; Pachamuthu, K.; Vankar, Y. D.
Synlett 2000, 1652–1654.
59. Teague, R. S. Adv. Carbohydr. Chem. Biochem. 1954, 9,
185–246.