Selective removal of anomeric O-acetate groups in carbohydrates using HClO4-SiO2

Article abstract of DOI:10.1016/j.tetlet.2006.03.050

A convenient methodology has been developed for the selective removal of the anomeric acyl group of carbohydrate derivatives using HClO₄-SiO₂ under acidic reaction conditions. Anomeric benzoyl groups can also be removed selectively following similar reaction conditions. The yields were excellent in all cases.

Full text of DOI:10.1016/j.tetlet.2006.03.050

Tetrahedron Letters 47 (2006) 3573–3576
Selective removal of anomeric O-acetate groups
I
in carbohydrates using HClO4–SiO2
Pallavi Tiwari and Anup Kumar Misra*
Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattar Manzil Palace,
Lucknow 226 001, UP, India
Received 23 January 2006; revised 27 February 2006; accepted 9 March 2006
Abstract—A convenient methodology has been developed for the selective removal of the anomeric acyl group of carbohydrate
derivatives using HClO4–SiO2 under acidic reaction conditions. Anomeric benzoyl groups can also be removed selectively following
similar reaction conditions. The yields were excellent in all cases.
Ó 2006 Elsevier Ltd. All rights reserved.
Suitably protected 1-hydroxy sugars or glycosyl hemi-
acetals are useful synthetic intermediates for the prepa-
ration of several glycosyl donors such as glycosyl
trichloroacetimidates,1 glycosyl fluorides2 and iodides3
and glycosylation reactions towards the preparation of
several bioactive molecules.4 Glycosyl hemiacetals have
successfully been used in dehydrative glycosylations
for the synthesis of several complex oligosaccharides.5
In general, protected glycosyl hemiacetals can be pre-
pared by (a) deacetylation of glycosyl-1-O-acetates;6
(b) acid hydrolysis of alkyl glycosides;7 (c) hydrolysis
of thioglycosides,8 etc. Conventional methods for ano-
meric O-deacetylation of per-O-acetylated carbohydrate
derivatives suffer from several shortcomings, which
include, the use of highly toxic reagents, for example,
hydrazine acetate,6a and heavy metal salts, for example,
bis(tributyltin)oxide,6b tributyltin methoxide6c and mer-
curic chloride/mercuric oxide.6d Although there are a
number of environmentally benign reagents (e.g., benz-
ylamine,6e sodium methoxide,6f ammonium salts,6g,h
piperidine,6i Al2O3,6j MgO,6k etc.) available for this
transformation, most require longer reaction times lead-
ing to non selective de-O-acetylation and time-consum-
ing purification steps. Therefore, the development of a
metal-free, less-toxic reaction protocol, avoiding
purification steps, would extend the scope of this
transformation.
Recently, we have applied considerable effort towards
the development of more environmentally benign cata-
lysts for several important organic transformations.9
During our study on the Helferich glycosylation of
per-O-acetylated sugars using HClO4 adsorbed on
SiO2,9b we observed that clean removal of the anomeric
acetate group was taking place in each case instead of
glycosylation. Taking cue from this observation, we ex-
plored the use of HClO4–SiO2 for the anomeric deacet-
ylation of 1-O-acetylated carbohydrate derivatives. We
herein disclose our findings on the anomeric de-O-acet-
ylation of carbohydrates under acidic reaction condi-
tions using HClO4–SiO2 (Scheme 1).
As a model system, per-O-acetylated b-D-glucose was
treated with HClO4–SiO2 varying the quantity of cata-
lyst and reaction solvent at 70 °C. It was observed that
use of 25 mg of HClO4–SiO2 (0.012 mmol of HClO4)
per mmol of per-O-acetylated b-D-glucose in acetonitrile
at 70 °C resulted in clean formation of the hemiacetal in
excellent yield without affecting other functional groups
present in the substrate. In order to establish the reaction
protocol, a series of protected mono- and disaccharides
Keywords: Carbohydrate; Deacetylation; Acetates; HClO4–SiO2;
Hemiacetals.
(OR)n
(OR)n
O
HClO4-SiO2
O
q CDRI Communication No. 6929.
OH
CH3CN, 70 oC, 1-2 h
OAc
*
Corresponding author. Tel.: +91 522 2612411 18; fax: +91 522
2623938; e-mail: akmisra69@rediffmail.com
Scheme 1.
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.050

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P. Tiwari, A. K. Misra / Tetrahedron Letters 47 (2006) 3573–3576
Table 1. Anomeric de-O-acylation of carbohydrate derivatives using
Table 1 (continued)
HClO4–SiO2
Entry
15
Substrates
Time Yield a/b
(h)
(%)
O
O
OAc
OAc
OH
Me
O
1.0
92
1:0
Entry
1
Substrates
Time
(h)
Yield
(%)
a/b
AcO
OAc
OAc
OAc
O
AcO
AcO
16
17
1.0
1.0
90
90
5:3
5:2
O
1.5
1.5
1.5
92
90
95
2:1
OAc
A
cO
OAc
OAc
AcO
OAc
OAc
OAc
O
O
OAc
AcO
AcO
AcO
2
3
2:1
5:2
OAc
AcO
OAc
OAc
O
OAc
O
AcO
AcO
AcO
OAc
18
19
2.0
2.0
92
95
2:1
2:1
O
AcO
O
AcO
OAc
AcO
OAc
OAc
OAc
AcO
AcO
OAc
OAc
O
A
cO
OAc
O
O
O
AcO
OAc
AcO
4
1.5
1.0
1.5
1.5
1.5
1.5
2.5
92
92
90
90
95
80
90
2:1
1:0
1:2
2:1
1:1
2:1
5:2
OAc
AcO
AcO
OAc
OAc
O
AcO
OAc
AcO
20
2.0
90
5:2
O
Ac
AcO
AcO
AcO
AcO
O
O
O
5
OAc
AcO
OAc
OAc
CAO: chloroacetyl group. All known compounds gave acceptable
1H NMR spectra, which matched the data reported in the literature.
OAc
O
AcO
6
OAc
AcO
NPhth
were subjected to the deacetylation conditions and
the results are presented in Table 1. The reaction was
equally effective for the removal of both a- and b-ace-
tates. Anomeric benzoyl groups could also be removed
in excellent yield using similar reaction conditions. Inter-
glycoside linkages remained unaffected. Pure products
could be obtained by removal of the catalyst by simple
filtration and evaporation of the solvent. In order to jus-
tify the role of moisture present in the solvent in the ano-
meric deacylation, a parallel reaction was performed
using distilled CH3CN in place of commercial CH3CN.
In both cases the yields of the product and reaction
times were almost similar indicating that the presence
of moisture in the solvent did not have any effect on
the reaction time and yield. No reaction or only very
low yields of the product were obtained using other com-
mon apolar solvents, for example, CH2Cl2, CHCl3,
THF, etc. A typical experimental procedure is as follows:
To a solution of 1-O-acetyl carbohydrate derivative
(1.0 mmol) in CH3CN (5 mL) was added HClO4–SiO2
(25 mg) and the reaction mixture was stirred at 70 °C
for the appropriate time as mentioned in Table 1. After
completion of the reaction (TLC), the reaction mixture
was filtered through a Celite bed and washed with
CH2Cl2 and the filtrate evaporated under reduced pres-
sure to furnish the pure glycosyl hemiacetal. Although,
the crude product was sufficiently pure, analytical sam-
ples were prepared by passing the crude reaction product
through a short column of SiO2. Caution: Although no
explosions were reported under these conditions, ex-
treme care has to be exercised for large-scale reactions
using HClO4–SiO2. The generation of the catalyst should
O
T
BDPS
O
AcO
AcO
7
OAc
OAc
OBz
O
BzO
BzO
8
OAc
OAc
OBz
OBn
O
BnO
BnO
9
OBn
BzO
BzO
OBz
O
10
BzO
OBz
OBz
O
OBz
11
12
2.5
1.5
85
85
1:0
5:2
OBz
OBz
OBz
CAO
CAO
O
Ac
O
OAc
OAc
OAc
OAc
Me
AcO
Me
O
13
14
1.0
1.0
90
82
1:1
2:1
OAc
OAc
OBn
O
OBn
be performed with special care and in
environment.
a safe
BnO

P. Tiwari, A. K. Misra / Tetrahedron Letters 47 (2006) 3573–3576
3575
OH
O
AcO
OAc
O
AcO
AcO
AcO
AcO
AcO
AcO
OAc
O
OAc
O
SPh
AcO
a,b
O
AcO
OAc
AcO
AcO
o
OAc
OC(NH)CCl3
O
HClO4-SiO2, CH2Cl2, MS-4A,
0 oC, 1 h, 85%
OAc
OAc
SPh
OAc
Scheme 2. Reagents and conditions: (a) HClO4–SiO2, CH3CN, 70 °C, 2 h, 95%; (b) CCl3CN, K2CO3, CH2Cl2, 80%.
Sambaiah, T.; Fanwick, P. E.; Cushman, M. Synthesis
2001, 1450–1452; (e) Conchie, J.; Levvy, G. A. Methods
Carbohydr. Chem. 1963, 2, 345–347; (f) Itoh, K.; Taka-
mura, H.; Watanbe, K.; Araki, Y.; Ishido, Y. Carbohydr.
Res. 1986, 156, 241–246; (g) Blazejewski, J.-C.; Dorme, R.;
Wakselman, C. Synthesis 1985, 1121–1122; (h) Mikamo,
M. Carbohydr. Res. 1989, 191, 150–153; (i) Rowell, R. M.;
Feather, M. S. Carbohydr. Res. 1967, 4, 486–491; (j)
Schneider, G.; Weisz-Vincze, I.; Vass, A.; Kovacs, K.
Tetrahedron Lett. 1972, 32, 3349–3352; (k) Herzig, J.;
Nudelman, A. Carbohydr. Res. 1986, 153, 162–167.
7. Koto, S.; Morishima, N.; Miyata, Y.; Zen, S. Bull. Chem.
Soc. Jpn. 1976, 49, 2639–2640.
In order to verify the synthetic utility of our method in
comparison to other reported protocols, peracetylated
galactose was transformed into its hemiacetal, which
was then converted to the trichloroacetimidate deriva-
tive using trichloroacetonitrile and K2CO3. The peracet-
ylated galactosyltrichloroacetimidate thus obtained was
further used in the glycosylation reaction using HClO4–
SiO2 as the glycosylation activator10 to prepare a novel
disaccharide thioglycoside, which can be used as a disac-
charide donor for the preparation of several oligosac-
charides (Scheme 2).11
8. (a) Xie, J.; Molina, A.; Czernecki, S. J. Carbohydr. Chem.
1999, 18, 481–498; (b) Barua, P. M. B.; Sahu, P. R.;
Mondal, E.; Bose, G.; Khan, A. T. Synlett 2002, 81–84; (c)
Uchiro, H.; Wakiyama, Y.; Mukaiyama, T. Chem. Lett.
1998, 567–568; (d) Misra, A. K.; Agnihotri, G. Carbohydr.
Res. 2004, 339, 885–890.
9. (a) Misra, A. K.; Tiwari, P.; Agnihotri, G. Synthesis 2005,
2, 260–266; (b) Misra, A. K.; Tiwari, P.; Madhusudan, S.
K. Carbohydr. Res. 2005, 340, 325–329; (c) Tiwari, P.;
Agnihotri, G.; Misra, A. K. Carbohydr. Res. 2005, 340,
749–752; (d) Kumar, R.; Tiwari, P.; Maulik, P. R.; Misra,
A. K. J. Mol. Catal. A: Chem. 2006, 247, 27–30.
In summary, we have introduced a new method for the
selective anomeric deacetylation or debenzoylation of
carbohydrate derivatives under acidic reaction condi-
tions. As the reaction does not require any toxic
reagents and chromatographic purification, this envi-
ronmentally benign reaction protocol should find appli-
cation in synthetic organic chemistry.
Acknowledgements
10. (a) Mukhopadhyaya, B.; Maurer, S. V.; Rudolph, N.; van
Well, R.; Russell, D.; Field, R. A. J. Org. Chem. 2005, 70,
9059–9062; (b) Du, Y.; Wei, G.; Cheng, S.; Hua, Y.;
Linhardt, R. J. Tetrahedron Lett. 2006, 47, 307–310.
11. 1,2,3,4,6-Penta-O-acetyl-b-D-galactose (585 mg, 1.5 mmol)
and HClO4–SiO2 (35 mg) were mixed in CH3CN (5 mL)
and stirred at 70 °C for 1.5 h. The reaction mixture was
filtered through Celite, rinsed with CH2Cl2 and concen-
trated. To a mixture of the crude product (496 mg,
1.42 mmol) and CCl3CN (570 lL, 5.68 mmol) in CH2Cl2
(5 mL) was added anhydrous K2CO3 (1.0 g) and the
reaction mixture was stirred at room temperature for 3 h.
After completion (TLC), the reaction mixture was filtered,
rinsed with CH2Cl2, concentrated and passed through a
short pad of SiO2 to give per-O-acetylated galactosyl
trichloroacetimidate (560 mg). To a mixture of per-O-
acetylated galactosyl trichloroacetimidate (560 mg,
1.1 mmol) and phenyl 2,3,4-tri-O-acetyl-1-thio-b-D-gluco-
pyranoside (398 mg, 1.0 mmol) in CH2Cl2 (5 mL) was
Instrumentation facilities from SAIF, CDRI are grate-
fully acknowledged. P.T. thanks CSIR, New Delhi, for
providing a Senior Research Fellowship. This project
was partly funded by the Department of Science and
Technology (DST), New Delhi (SR/FTP/CSA-10/2002),
India.
References and notes
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Milat, M.-L.; Sinay, P. J. Am. Chem. Soc. 1977, 99, 6762–
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6763; (b) Schmidt, R. R.; Jung, K.-H. In Preparative
Carbohydrate Chemistry; Hanessian, S., Ed.; Marcel
Dekker: New York, 1996; pp 283–312.
2. Caputo, R.; Kunz, H.; Mastroianni, D.; Palumbo, G.;
Pedatella, S.; Solla, F. Eur. J. Org. Chem. 1999, 3147–
3150.
3. Yokoyama, M. Carbohydr. Res. 2000, 327, 5–14.
4. (a) Schmidt, R. R.; Klotz, W. Synlett 1991, 168–170; (b)
Schmidt, R. R. Angew. Chem., Int. Ed. Engl. 1986, 25,
212–235.
5. (a) Garcia, B. A.; Poole, J. L.; Gin, D. Y. J. Am. Chem.
Soc. 1997, 119, 7597–7598; (b) Garcia, B. A.; Gin, D. Y. J.
Am. Chem. Soc. 2000, 122, 4269–4279; (c) Garcia, B. A.;
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M.; Poole, J. L.; Gin, D. Y. Angew. Chem., Int. Ed. 2001,
40, 414–417.
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Res. 1975, 39, 368–373; (b) Watanbe, K.; Itoh, K.; Araki,
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˚
added powdered MS-4 A (500 mg) and the reaction
mixture was stirred under Ar for 30 min at 0 °C. To the
cooled reaction mixture was added HClO4–SiO2 (30 mg)
and the reaction mixture was stirred at 0 °C for 1 h. After
completion of the reaction (TLC), the reaction mixture
was filtered through a Celite bed and washed with CH2Cl2.
The organic layer was washed with satd aq NaHCO3
and water, dried (Na2SO4) and concentrated. Column
chromatography of the crude product over SiO2 using
hexane–EtOAc (3:1) furnished phenyl (2,3,4,6-tetra-O-
acetyl-b-D-galacto-pyranosyl)-(1!6)-2,3,4-tri-O-acetyl-1-
thio-b-D-glucopyranoside (618 mg, 85%). 1H NMR
(CDCl3, 300 MHz): d 7.48–7.32 (m, 5H, aromatic pro-
tons), 5.39–5.33 (dd, J = 9.5 and 2.4 Hz, 1H), 5.28 (d,
J = 7.9 Hz, 1H), 5.21–5.17 (m, 1H), 5.15–5.02 (m, 1H),

3576
P. Tiwari, A. K. Misra / Tetrahedron Letters 47 (2006) 3573–3576
5.00–4.80 (m, 3H), 4.73–4.65 (t, J = 8.7 Hz each, 1H),
(75 MHz, CDCl3): d 171.2, 170.6, 170.4, 170.0, 169.4 (2C),
168.9, 132.9–128.1 (aromatic carbons), 100.9, 85.4, 77.3,
76.6, 76.0, 73.7, 70.6, 69.0, 68.5, 68.3, 61.1, 60.7, 20.6 (2C),
20.5 (2C), 20.3 (2C), 20.0.
4.54–4.48 (dd, J = 8.8 Hz, 8.8 Hz, 1H), 4.17–4.06 (m, 2H),
3.89–3.82 (m, 1H), 3.74–3.67 (m, 2H), 2.10, 2.08, 2.07,
2.06, 2.03, 1.98, 1.96 (7s, 21H, 7COCH3); 13C NMR