Regioselective anomeric deacetylation of peracetylated glycopyranoses

Article abstract of DOI:10.1071/CH03057

A simple and mild method for regioselective anomeric deacetylation of peracetylated glycopyranoses using copper(II) acetate dihydrate and methanol/water (9:1) is described.

Full text of DOI:10.1071/CH03057

CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2003, 56, 909–911
Regioselective Anomeric Deacetylation of Peracetylated Glycopyranoses
A
A
A,B
Kankan Bhaumik, Paresh D. Salgaonkar and K. G. Akamanchi
A
Department of Pharmaceutical Sciences and Technology, UICT, Matunga, Mumbai 400019, India.
Author to whom correspondence should be addressed (e-mail: kgap@rediffmail.com).
B
A simple and mild method for regioselective anomeric deacetylation of peracetylated glycopyranoses using
copper(ii) acetate dihydrate and methanol/water (9 : 1) is described.
Manuscript received: 26 February 2003.
Final version: 4 May 2003.
Introduction
deacetylation of peracetylated sugars. In our research, we
have developed a simple and relatively inexpensive method
for this goal. The reaction was performed by refluxing the
peracetylated sugar for 3–4 h with copper(ii) acetate dihy-
drate and aqueous methanol to effect a smooth, regioselective
anomeric deacetylation.
In organic synthesis, selective protection and deprotection of
polyfunctional molecules are critical problems. In carbohy-
drate chemistry these problems are more crucial owing to the
presence of multiple hydroxyl functions of very similar reac-
tivity. Fully protected sugars, having a free hydroxyl group
at the anomeric carbon atom, serve as important domains
for the synthesis of oligosaccharides and glycoconjugates,
such as glycoproteins and glycolipids, and other such
carbohydrate-based biologically active molecules. In addi-
tion, the free hydroxyl group at the anomeric carbon can be
functionalized so as to provide reactive glycosyl donors,
such as glycosyl imidates, fluorides, phosphates, xanthates,
and others.
There is a good number of reagents or catalysts reported
in the literature for the selective anomeric deacetylation
of peracetylated sugars. Some of these methods involve
Results and Discussion
[
1]
[
2]
Treatment of α-d-glucose pentaacetate, β-d-glucose penta-
acetate, α-d-galactose pentaacetate, β-d-rhamnose tetraac-
etate, β-d-xylose tetraacetate, and α-l-arabinose tetraacetate
with copper(ii) acetate dihydrate in aqueous methanol
at reflux temperature for 3–4 h afforded exclusively the
anomeric deacetylated products. The products were iso-
lated by extraction with ethyl acetate, followed by silica-gel
column purification. These results are summarized in Table 1,
entries 1–6, respectively.
[
3]
[
4]
−
direct hydrolysis using (a) a Lewis acid, mainly BF
In order to extend the scope of the developed system,
the reactions were performed on peracetylated disaccha-
rides, α/β-maltose octaacetate (entry 7) and α/β-lactose octa-
acetate(entry8). Theseoctaacetatesalsounderwentanomeric
deacetylation smoothly. The physical constants and spectral
data of all the compounds were in agreement with those
3
[5]
[6]
[7]
etherate, tin(iv) chloride, or AlX3(Cl,Br); (b) nitro-
[
8a–8c]
geneous nucleophiles, such as ammonia,
ammo-
[8d]
[9]
benzylamine, ethylene diamine,
[10]
nium carbonate,
[
11]
[12]
[13]
piperidine, hydrazine, hydrazinehydrate, hydrazine
acetate,
[14]
[15]
guanidine, or guanidinium nitrate;
(c) other
[16]
[17]
[19a]
[8a,14a]
entries 5–6,
reagent systems like KCN/KOH,
HgO/HgCl2,
or
reported in the literature (entries 1–4,
and entries 7–8
[18]
[19]
[11,19b,19c]
MgO;
or (d) enzymes.
This anomeric deacetyla-
). In all of these cases (entries 1–8),
tion can also be achieved through indirect hydrolysis by
converting the anomeric acetate to a more reactive func-
20–25% of the unreacted starting peracetylated sugar with
some amounts of a mixture of other deacetylated products
were recovered during column purification. Yields (56–67%)
obtained by our method are quite comparable to those of
[20]
[16,21]
stannyl ether, or
tionality like a glycosyl halide,
[22]
N-phenylglycopyranosylamine.
The literature procedures sometimes suffer from the cum-
bersome preparation of, for example, glycosyl halides and
the requirement of anhydrous conditions. Most of the pro-
cedures require basic conditions and excess reagents, and as
the reaction progresses the regioselectivity at C1 decreases.
The hazardous nature of mercury(ii) salts limits the use of
HgO/HgCl2, a relatively mild and neutral system.
other systems: HgO/HgCl (60–74%) and MgO (50–75%).
Although nitrogenous nucleophiles give higher yields of
2
anomeric decetylated products, the major drawback in these
systems is the higher basicity of the reaction medium.
Under the reaction conditions mentioned, the most com-
mon carbohydrate protective groups, such as O-benzyl (entry
9) and acetonide (entry 10), remain unaffected.
Considering all these facts there is an incentive for
developing mild, neutral systems for selective anomeric
Certain control experiments were performed while devel-
oping the system. In the absence of copper(ii) acetate, no
©
CSIRO 2003
10.1071/CH03057
0004-9425/03/090909

9
10
K. Bhaumik, P. D. Salgaonkar and K. G. Akamanchi
Table 1. Anomeric deacetylation of peracetylated sugars using copper(ii) acetate dihydrate and methanol/water (9 : 1)
Entry
Substrate
Product
Isolated yield [%]
Time
[h]
A
(
α : β ratio)
OAc
OAc
O
AcO
AcO
O
1
2
AcO
AcO
64 (2.3 : 1)
4.0
4.0
OAc
OAc
OAc
OH
OH
OAc
OAc
O
O
AcO
AcO
AcO
AcO
67 (1 : 1)
OAc
OAc
OAc
OAc OAc
OAc OAc
O
O
3
4
AcO
64 (1.8 : 1)
62 (1.5 : 1)
4.5
3.5
OAc
AcO
OAc
OAc
OH
H C OAc
3
H C OAc
O
3
O
AcO
AcO
AcO
AcO
OAc
OAc
OH
O
O
AcO
AcO
AcO
AcO
58 (3.5 : 1)
56 (1 : 1)
3.5
3.5
5
6
OAc
OAc OH
OAc
OAc
O
O
OAc
AcO
AcO
OAc
OAc OH
OAc
OAc
O
O
AcO
AcO
AcO
AcO
OAc
OAc
7
8
9
61 (1 : 4)
59 (1 : 1)
–
3.0
3.0
6.0
OAc
O
OAc
O
O
AcO
O
AcO
OAc
OAc
OAc
OH
OAc OAc
OAc OAc
OAc OH
O
OAc OAc
O
O
O
AcO
O
AcO
O
AcO
AcO
OAc
OAc
OAc
OAc
OBn OBn
–
–
O
BnO
OBn
OBn
O
O
O
OH
1
0
–
6.0
O
O
A
1
The α : β ratio was determined by H NMR (200 and 500 MHz) spectroscopy.
anomeric deacetylation occurred even after refluxing for
h. This study clearly indicated that the Lewis acidity of
copper(ii) acetate was prerequisite for affecting the deacety-
using anhydrous copper(ii) acetate. No significant amount
of anomeric-deacetylated product was isolated even after
refluxing for 8 h, indicating that the deacetylation may not
be occurring by trans-esterification but rather by hydrolysis.
6
lation. The reaction was carried out in anhydrous methanol

Regioselective Anomeric Deacetylation of Peracetylated Glycopyranoses
911
The role of methanol could be to act as a co-solvent to solu-
bilize the substrates that otherwise are completely insoluble
in water, even in the presence of copper(ii) acetate.
In conclusion, a new system for selective anomeric
deacetylation has been developed that is simple, mild, and
cheap.
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Experimental
[
1
All the reagents were commercially available and used as received. H
1
1
3
and C NMR spectra were recorded on 200 and 500 MHz instruments.
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[
Typical Procedure: Anomeric Deacetylation of
Penta-O-acetyl-β- -glucopyranose (Table 1, entry 2)
D
The glucose pentaacetate (0.5 g, 1.28 mmol) was dissolved in 20 mL of
methanol/water (9 : 1). Copper(ii) acetate dihydrate (0.28 g, 1.28 mmol)
was added and the mixture was refluxed for 4 h (monitored by thin layer
chromatography). The reaction mixture was cooled to room tempera-
ture then filtered, and the filtrate was distilled under reduced pressure
to remove methanol. The residue was diluted with 50 mL of water
and extracted (2 × 50 mL) with ethyl acetate. The organic phase was
dried over sodium sulfate and concentrated under reduced pressure.
The viscous residue obtained was purified by dry silica-gel column
chromatography using ethyl acetate/hexane (15 : 85) to yield a syrup
of the anomeric deacetylated product, 0.28 g (67%). δH (CDCl3) 5.44
[9] C. Ferrer Salat, P. Axerio Agneseti, Chem. Abstr. 1977, 87,
23 683k.
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[11] R. M. Rowell, M. S. Feather, Carbohydr. Res. 1967, 4, 486.
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J. Chem. 1996, 49, 293. (b) H. C. Kolb, Bioorg. Med. Chem.
Lett. 1997, 7, 2627.
[13] R. Khan, P. A. Konowicz, L. Gardossi, M. Matulova, S. Paoletti,
Tetrahedron Lett. 1994, 35, 4247.
(
4
0.5 H, d, J 4.0, Hα1), 5.26–5.22 (1 H, m, H3), 5.10–5.07 (1 H, m, H4),
.89–4.85 (1 H, m, H2), 4.73 (0.5 H, d, J 8.0, Hβ1), 4.30–4.08 (1 H,
[14] (a) G. Excoffier, D. Gagnaire, J. P. Utille, Carbohydr. Res. 1975,
39, 368. (b) T. Ren, D. Liu, Tetrahedron Lett. 1999, 40, 7621.
[15] N. Kunesch, C. Miet, J. Poisson, Tetrahedron Lett. 1987, 28,
3569.
ꢀ
m, H5), 3.90–3.75 (2 H, m, H6 and H6 ), 2.08–2.00 (12 H, s, CH3CO).
δC (CDCl3) 170.5–168.7 (CH3CO), 95.0 (C1β), 89.0 (C1α), 72.0 (C3),
7
1.7, 70.9 (C2), 69.7 (C4), 66.5 (C5), 61.7 (C6), 20.11 (CH3CO).
[16] K. Watanabe, K. Itoh, Y. Araki, Y. Ishido, Carbohydr. Res.
1
986, 154, 165.
[
[
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J. Org. Chem. 1988, 53, 4939. (b) R. Khan, L. Gropen, P.
A. Konowicz, M. Matulova, S. Paoletti, Tetrahedron Lett. 1993,
Acknowledgments
K.B. wishes to thank UGC, New Delhi, and P.D.S. wishes
to thank CSIR, New Delhi, for fellowships. We gratefully
acknowledge TIFR, Mumbai, for providing the high-field
NMR facility.
3
4, 7767. (c) L. Gardossi, R. Khan, P. A. Konowicz, L. Gropen,
B. S. Paulsen, J. Mol. Catal. B: Enzym. 1999, 6, 89.
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6
3, 587. (b) A. Georg, Helv. Chim. Acta 1932, 15, 924. (c)
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