Unprecedented transformation of thioglycosides to their corresponding 1-O-acetates in the presence of HClO4-SiO2

Article abstract of DOI:10.1080/07328300600860153

An unprecedented conversion of thioalkyl/aryl glycoside to the corresponding 1-O-acetates has been described using acetic anhydride and HClO₄-SiO₂ at rt. Although this transformation does not play an important role in the oligosaccha

Full text of DOI:10.1080/07328300600860153

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Unprecedented Transformation of
Thioglycosides to Their Corresponding
1‐O‐Acetates in the Presence of HClO4‐SiO2
Geetanjali Agnihotri a , Pallavi Tiwari a & Anup Kumar Misra a
a Medicinal and Process Chemistry Division , Central Drug Research
Institute , Lucknow, UP, India
Published online: 22 Sep 2006.
To cite this article: Geetanjali Agnihotri , Pallavi Tiwari & Anup Kumar Misra (2006) Unprecedented
Transformation of Thioglycosides to Their Corresponding 1‐O‐Acetates in the Presence of HClO4‐SiO2 , Journal
of Carbohydrate Chemistry, 25:6, 491-498, DOI: 10.1080/07328300600860153
To link to this article: http://dx.doi.org/10.1080/07328300600860153
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Journal of Carbohydrate Chemistry, 25:491–498, 2006
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300600860153
Unprecedented
Transformation
of Thioglycosides to
Their Corresponding
1-O-Acetates in the
Presence of HClO4-SiO2
§
Geetanjali Agnihotri, Pallavi Tiwari, and Anup Kumar Misra
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow,
UP, India
An unprecedented conversion of thioalkyl/aryl glycoside to the corresponding 1-O-
acetates has been described using acetic anhydride and HClO4-SiO2 at rt. Although
this transformation does not play an important role in the oligosaccharide synthesis
in comparison to its reverse transformation, this gives useful information in selecting
the reaction condition for the synthesis of oligosaccharides. The yields were excellent
in all cases.
Keywords Carbohydrate, Thioglycosides, Acetates, One-pot, HClO4-SiO2
INTRODUCTION
The role of carbohydrates in several biological processes is now well established.
Although carbohydrates are naturally abundant, the limited supply of complex
carbohydrates forced us to synthesize them chemically. A plethora of glycosyla-
tion techniques is now available in the literature using a wide range of glycosyl
donors used in the glycosylation reactions.[1] Among several glycoside donors
Received March 23, 2006; accepted June 5, 2006.
§C.D.R.I. communication no. 6979.
Authors contributed equally to this work.
Address correspondence to Anup Kumar Misra, Medicinal and Process Chemistry
Division, Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226001,
UP, India. E-mail: akmisra69@rediffmail.com
491

G. Agnihotri et al.
492
used in the oligosaccharide syntheses, thioglycosides are widely used because of
their high degree of stability to many reaction conditions.[2] As in the case of
thioglycosides, glycosyl-1-O-acetates[3] have also been used in several oligosac-
charide syntheses. Besides their use as glycosyl donors under Lewis acid
promoted glycosylation,[3] they find applications in the preparation of glycosyl
halides.[4] Conventional method for the preparation of these compounds
consists of a two-step reaction sequence, which includes removal of a temporary
anomeric protecting group[5] (methyl, benzyl, allyl, trimethylsilylethyl,
thioalkyl, thioaryl, etc.) followed by acetylation of the anomeric hydroxyl
group. Although thioglycosides have widely been used as glycosyl donors for
the successful outcome of several complex oligosaccharides, there are few
reports on the unusual behavior of thioglycosides, which results in intermole-
cular aglycon transfer instead of formation of any glycosylated products.[6]
Recently we spent a considerable effort toward the development of more
environmentally friendly catalysts for several important organic transform-
ations.[7] During our study on the acetylation of carbohydrate derivatives
using acetic anhydride and HClO4 adsorbed on SiO2 (HClO4-SiO2),[7a] we
observed that in the case of thioglycosides, a clean substitution of anomeric
thioalkyl or thioaryl group by an acetate group was taking place with time.
In several circumstances, use of thioglycosides in the glycosylation reactions
did not produce the expected glycosides in our hands although both donor
and acceptor have been consumed during the reaction conditions. In order to
add information about some unusual behaviors of thioglycosides, we sought
to explore the use of HClO4-SiO2 for the direct conversion of thioglycosides to
the corresponding 1-O-acetylated carbohydrate derivatives. We herein
disclose our finding on the direct conversion of thioglycoside to the glycosyl
anomeric acetates using HClO4-SiO2 without using any solvent.
RESULTS AND DISCUSSION
As a model system, ethyl 2,3,4,6-tetra-O-acetyl-1-thio-b-D-glucopyranoside
was treated with acetic anhydride (1 mL/mmol of substrate) in the presence
of HClO4-SiO2 (50 mg/mmol of the substrate) at rt. An exothermic reaction
started immediately and a quantitative yield of D-glucosepentaacetate was
obtained in 20 min. After a series of experimentation, it was observed that
use of 25 mg of HClO4-SiO2 (0.012 mmol of HClO4) per mmol of thioglycoside
in acetic anhydride (1 mL/mmol) at rt could result a clean formation of
Scheme 1

Unprecedented Transformation of Thioglycosides
493
glycosyl 1-O-acetate in excellent yield (Sch. 1). In order to establish the reaction
protocol, a series of differentially protected mono- and disaccharides have been
treated under this reaction condition and the results are presented in Table 1.
The reaction condition is equally effective for the replacement of thioaryl
groups. It is noteworthy that 1,2-cis thioglycosides (entries 3 and 13, Table 1)
also resulted in anomeric acetates in a similar fashion as it occured in the
case of 1,2-trans thioglycosides. Interglycoside linkages remain unaffected
under the reaction condition. Pure product can be obtained by removal of the
catalyst through filtration and evaporation of the solvent.
In summary, we are disclosing an unprecedented transformation of thiogly-
cosides to their corresponding glycosyl 1-O-acetates using HClO4-SiO2 very
rapidly. Although this transformation is less important to the oligosaccharide
synthesis as the glycosyl acetate is a less reactive donor than its thioglycoside
counterpart, this could justify the failure of many glycosylation reactions using
thioglycosides as donors. Above all, the reaction is very fast and proceeds well
without requirement of any added solvent. This transformation will be con-
sidered to explain the unusual behavior of thioglycosides in the synthetic
carbohydrate chemistry.
EXPERIMENTAL
General methods: General methods are the same as used previously.[5d]
Preparation of HClO4-SiO2: HClO4 (1.8 g, 12.5 mmol, as a 70% aq solution)
was added to a suspension of SiO2 (230–400 mesh, 23.7 g) in Et2O (70.0 mL).
The mixture was concentrated and the residue was heated at 1008C for 72 h
under vacuum to furnish HClO4-SiO2 (0.5 mmol/g) as a free-flowing powder.
Caution!: Although no explosions were reported under these conditions,
extreme care has to be exercised for large-scale reactions.
Typical experimental procedure is as follows: To a solution of thioglyco-
sides (1.0 mmol) in acetic anhydride (1.0 mL) was added HClO4-SiO2 (25 mg)
and the reaction mixture was stirred at rt for an appropriate time (Table 1).
After completion of the reaction (TLC), the reaction mixture was filtered
through a celite bed and diluted with CH2Cl2.The organic layer was washed
with satd. aq. NaHCO3 and water, and evaporated under reduced pressure to
furnish crude glycosyl 1-O-acetates, which were further purified over SiO2
using hexane-EtOAc (1 : 1) as eluent.
1,2-Di-O-acetyl-3,4,6-tri-O-benzoyl-a-D-glucopyranose (entry 14, Table 1):
Yellow oil; 1H NMR (300 MHz, CDCl3): d 8.04–7.90 (m, 6H, aromatic protons),
7.58–7.33 (m, 9H, aromatic protons), 6.46 (d, J ¼ 3.3 Hz, 1H, H-1), 6.01–5.95
(dd, J ¼ 10.2 and 9.9 Hz, 1H, H-3), 5.73–5.66 (dd, J ¼ 9.9 and 3.6 Hz, 1H,

G. Agnihotri et al.
494
Table 1: Direct conversion of thioglycosides to corresponding glycosyl 1-O-
acetates using acetic anhydride and HClO4-SiO2.
Entry
Substrates
Time (min) Yield (%) a/b
Ref
1
20
30
30
98
96
95
4:1
6:1
a
[8]
2
3
[8]
[8]
4
5
6
7
8
30
20
30
30
15
96
96
95
95
95
5:1
6:1
6:1
5:1
6:1
[8]
[8]
[8]
[8]
[8]
9
20
20
92
96
a
[8]
[9]
10
1:4
(continued)

Unprecedented Transformation of Thioglycosides
495
Table 1: Continued.
Entry
Substrates
Time (min) Yield (%) a/b
Ref
11
30
98
1:4
[9]
12
15
92
a
[8]
13
14
25
20
90
90
a
a
[8]
[8]
15
16
17
18
10
15
10
30
90
95
90
96
8:1
a
[10]
—
a
—
5:1
[11]
19
20
30
30
95
96
4:1
4:1
[12]
[13]
Products of all known compounds gave acceptable 1H NMR spectra that matched data
reported in the literature.

G. Agnihotri et al.
496
H-2), 5.41–5.36 (dd, J ¼ 9.9 and 9.6 Hz, 1H, H-4), 4.65 (d, J ¼ 11.4 Hz, 1H,
H-6a), 4.49–4.38 (m, 2H, H-6b and H-5), 2.27, 1.95 (2 s, 6H, 2 COCH3). 13C
NMR (50 MHz, CDCl3): d 169.6, 168.7, 166.0, 165.8, 165.2, 133.7–128.7
(aromatic carbons), 89.7, 70.7, 70.5, 69.8, 69.3, 62.8, 21.8, 20.7; IR (neat):
2961, 1756, 1724, 1648, 1599, 1451, 1376, 1271, 1231, 1097, 1067, 1026,
710 cm21; [a]D25 þ107.48 (c 1.0, CHCl3); ESI-MS: 599 [M þ Na]; Anal. calcd.
for C31H28O11 (576): C, 64.58; H, 4.90; found C, 64.35 H, 5.12.
1,2-Di-O-acetyl-3,4,6-tri-O-benzyl-a-D-glucopyranose (entry 15, Table 1):
Yellow oil; 1H NMR (300 MHz, CDCl3): d 7.32–7.14 (m, 15 H, aromatic
protons), 6.29 (d, J ¼ 3.6 Hz, 1H, H-1), 5.07–5.02 (dd, J ¼ 9.3 and 3.6 Hz,
1H, H-2), 4.85–4.78 (m, 6H, PhCH2), 4.01–3.95 (dd, J ¼ 9.6 and 9.3 Hz, 1H,
H-3), 3.83–3.80 (m, 1H, H-4), 3.78–3.53 (m, 3H, H-5, H-6ab), 2.10, 2.07 (2 s,
6H, 2COCH3). 13C NMR (50 MHz, CDCl3): d 169.6, 169.3, 138.7–127.8
(aromatic carbons), 90.3, 80.3, 77.6, 77.5, 76.2, 75.6, 75.3, 72.5, 68.4, 21.2,
21.0; IR (neat): 2923, 2341, 1751, 1596, 1355, 1228, 1062, 754 cm21; [a]D25
þ164.18 (c 1.0, CHCl3); ESI-MS: 557 [M þ Na]; Anal. calcd. for C31H34O8
(534): C, 69.65; H, 6.41; found C, 69.40; H, 6.60.
ACKNOWLEDGEMENTS
Instrumentation facilities from SAIF, CDRI are gratefully acknowledged. G.A.
and P.T. thank CSIR, New Delhi, for providing Senior Research Fellowships.
This project was partly funded by Department of Science and Technology
(DST), New Delhi (SR/FTP/CSA-10/2002), India.
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