A useful and convenient synthetic procedure for hydrolysis of thioglycosides

Article abstract of DOI:10.1246/cl.2002.210

Various thioglycosides 1 are smoothly hydrolyzed chemo-selectively to the corresponding 1-hydroxy sugars 2 in good yields at 0-5°C by employing (NH₄)₆Mo₇O₂₄· 4H₂O-H₂O₂ or H₂MoO₄·H₂O-H₂O₂ to promote oxidation of ammonium bromide in the presence of perchloric acid in CH₂Cl₂-H₂O solvent system. Mild conditions, good yields, no side reactions such as bromination either at the anomeric position or double bond, and even oxidation at the sulfur are some of the major advantages.

Full text of DOI:10.1246/cl.2002.210

210
Chemistry Letters 2002
A Useful and Convenient Synthetic Procedure for Hydrolysis of Thioglycosides
Ejabul Mondal, Pankaj M. Bujar Barua, Gopal Bose, and Abu T. Khanꢀ
Department of Chemistry, Indian Institute of Technology, North Guwahati, Guwahati 781039, Assam, India
(Received October 26, 2001; CL-011060)
Various thioglycosides 1 are smoothly hydrolyzed chemo-
catalyzed oxidation of ammonium bromide17a and bromination
of various organic substrates by utilizing V2O5-H2O2 to promote
oxidation of n-tetrabutylammonium bromide.17b Taking cues
from the knowledge of the reactivity of diperoxomolybdate(VI)
for oxidation of bromide,18 we have now developed an
environmentally acceptable protocol for hydrolysis of thioglyco-
sides by employing ammonium heptamolybdate tetrahydrate or
molybdic acid, hydrogen peroxide in the presence of perchloric
acid, and ammonium bromide (Scheme 1). The promoter
ammonium heptamolybdate or molybdic acid is used for the
oxidation of ammonium bromide by H2O2 in the presence of
perchloric acid and all these chemicals are environmentally
acceptable.
selectively to the corresponding 1-hydroxy sugars 2 in good
yields at 0–5 ꢁC by employing ðNH4Þ6Mo7O24Á4H2O-H2O2 or
H2MoO4ÁH2O-H2O2 to promote oxidation of ammonium bro-
mide in the presence of perchloric acid in CH2Cl2-H2O solvent
system. Mild conditions, good yields, no side reactions such as
bromination either at the anomeric position or double bond, and
even oxidation at the sulfur are some of the major advantages.
Suitably protected 1-hydroxy sugars are useful building
blocks for the preparation of various glycosyl donors, which are
extensively used for glycosylation reactions in carbohydrate
chemistry.1{5 The usual standard procedure for the preparation of
protected 1-hydroxy sugars are as follows: i) they can be
prepared, for instance 2a and 2b, from their corresponding
1,2,3,4,6-penta-O-acetyl sugars by selective hydrolysis of the
acetate group at the anomeric position using hydrazine,6 which is
highly toxic; ii) they can also be obtained by acid catalyzed
hydrolysis of benzylated methyl ꢀ-glycosides, for instance 2c7
and 2d,8 which are provided with relatively low yield; and iii)
they can be easily accessed from their respective thioglycosides
by hydrolysis.9 The preparation of 1-hydroxy sugars starting from
their corresponding thioglycosides is more convenient because of
its excellent chemical stability, which provides efficient tempor-
ary protection at the anomeric position while carrying out the
protecting group manipulations at the other positions.10 On the
other hand, thioglycosides are also valuable starting material for
oligosaccharide synthesis.11 In addition, the hydrolysis of 1-
thioglycosides leads to the corresponding hemiacetals, which
may either be converted into the better glycosyl donors such as
trichloroacetimidates12 or directly converted into the other stable
protecting groups such as thexyldimethylsilyl (TDS), so that it is
not involved in the glycosidation reactions when both acceptor
and donor sugar units are armed 1-thioglycosides.13 Hence, the
hydrolysis of thioglycosides is very often encountered in
preparing desired starting materials for oligosaccharide synthesis.
The methods are available so far for hydrolysis of thioglycosides:
i) by employing thiophilic reagents such as heavy metal salts,14
which are inherently toxic ii) using N-bromosuccinimide15 in
acetone-H2O iii) by utilizing a catalytic amount of trityl
tetrakis(pentafluorophenyl)borate in combination with a Lewis
acid catalyst and sodium periodate.16 All these existing
procedures have some drawbacks such as providing relatively
low yield,14 requiring molar excess of reagents, sometimes to be
difficult to obtain hydrolyzed product if NBS is not recrystallized
prior to use,15 also requiring more expensive reagents and
relatively harsh reaction conditions.16 Therefore, what is needed
is a methodology that is environmentally benign, mild, clean, and
yet efficient.
(NH4)6Mo7O24 4H2O H2O2
or
H2MoO4 H2O H2O2
O
O
SEt
HClO4 / NH4Br
OH
1
2
CH2Cl2 H2O, 0 5
Scheme 1.
Subsequently, various reaction conditions were sampled,
with the result that a (1 : 3 : 0:4 : 0:4 : 13) substrate/ammonium
bromide/ammonium heptamolybdate/perchloric acid/hydrogen
peroxide in dichloromethane-water solvent (2 : 1, 10 mL per
mmol of substrate) gave best results (Method A). Interestingly,
the similar hydrolysis could also be achieved by using molybdic
acid instead of ammonium heptamolybdate with the same molar
ratio of other reagents (Method B). By using the above typical
reaction protocol,19 the compound ethyl 2,3,4,6-tetra-O-acetyl-1-
thio-ꢁ-D-glucopyranoside (1a) reacted smoothly to give the
hydrolyzed product 2,3,4,6-tetra-O-acetyl-D-glucopyranose (2a)
in 82% yield. The hydrolyzed product 2a was also prepared from
the compound 1a in 87% yield by following the Method B.
Likewise, various thioglycosides 1b-1k were hydrolyzed easily to
the desired compounds 1-hydroxy sugars 2b-2k in good yields
under identical reaction conditions. The results are summarized in
the Table 1 and the hydrolyzed products are fully characterized
by 1H-NMR, 13C-NMR, specific rotation and elemental analyses.
In this procedure, direct oxidation of sulfur by hydrogen peroxide
was not possible which had already been investigated by others.20
It is noteworthy to mention that we have not noticed any
bromination at the double bond or at the anomeric position.
The formation of the hydrolyzed products from their
corresponding thioglycosides can be rationalized18 as follows.
Ammonium heptamolybdate or molybdic acid reacts with H2O2
in the presence of HClO4 to generate diperoxomolybdate(VI),
which oxidizes the bromide (BrÀ) to Brþ (which might also exist
À
as Br2 or Br3 ). Then the reactive species Brþ reacts with sulfur to
form bromosulfonium complex, which is finally hydrolyzed by
water to the corresponding 1-hyroxy sugars.
In summary, we have devised a simple and useful synthetic
protocol for hydrolysis of thioglycosides to the corresponding 1-
Very recently we have reported the useful synthetic methods
for deprotection of dithioacetals by employing V2O5-H2O2
Copyright Ó 2002 The Chemical Society of Japan

Chemistry Letters 2002
211
H. Paulsen, Angew. Chem., Int. Ed. Engl., 29, 823 (1990).
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Ann. Chem., 1961, 649. b) C. P. J. Glaudemans and H. G.
Fletcher, Jr., in ‘‘Methods in Carbohydrate Chemistry,’’ ed.
by R. L. Whistler and M. Wolfrom, Academic Press, New
York (1972), Vol. VI, pp 372–373. c) L. Kaesbeck and H.
Kessler, Liebigs Ann./Recl., 1997, 169.
Table 1. Hydrolysis of various thioglycosides using ammonium
bromide promoted by (NH4Þ6Mo7O24Á4H2O-H2O2 or
H2MoO4ÁH2O-H2O2 in the presence of perchloric acid
3
4
Entry
Substrate (1)
Time
in h
Product (2)a
Yieldb
5
6
7
OAc
O
OAc
O
3.5c
5.5d
82
87
a
AcO
AcO
AcO
AcO
SEt
OH
AcO
OAc
AcO
OAc
OAc
OAc
2.5c
75
b
c
d
e
f
O
O
AcO
SEt
AcO
OH
AcO
OBn
AcO
OBn
5.5c
4.0d
81
84
O
O
BnO
BnO
BnO
SEt
SEt
BnO
OH
BnO
OBn
BnO
OBn
BnO
BnO
8
9
a) P. W. Austin, F. E. Hardy, J. H. Buchnan, and J. Baddiley,
J. Org. Chem., 30, 1419 (1965). b) S. Koto, N. Morishima, Y.
Miyata, and S. Zen, Bull. Chem. Soc. Jpn., 49, 2639 (1976).
G.-J. Boons, in ‘‘Carbohydrate Chemistry,’’ ed. by G.-J.
Boons, Blackie Academic and Professional, London (1998)
pp 126–143 and references therein.
0.75c
85
O
O
BnO
BzO
BnO
BzO
OH
BnO
BnO
OBz
OBz
8.0c
5.0d
89
85
O
O
BzO
SEt
SEt
SEt
BzO
OH
BzO
OBn
BzO
OBn
1.5c
6.0c
82
80
O
O
AcO
BnO
AcO
BnO
10 M. Mueller, U. Huchel, A. Geyer, and R. R. Schmidt, J. Org.
Chem., 64, 6190 (1999).
OH
BnO
OBn
BnO
OBn
O
O
11 P. J. Garegg, Adv. Carb. Chem. Biochem., 52, 179 (1997).
12R. R. Schmidt, Angew. Chem., Int. Ed. Engl., 25, 212 (1986).
13 A. T. Khan and R. R. Schmidt, unpublished results.
14 For example: T. Ogawa, K. Koike, M. Numata, M. Sugimoto,
and M. Nakahara, Japanese Patent, JP8835591 (1988).
15 a) M. S. Motawis, J. Marcussan, and B. L. Moeller, J.
Carbohydr. Chem., 14, 1279 (1995). b) L. Kaesbeck, and H.
Kessler, Liebigs Ann./Recl., 1997, 169.
16 H. Uchiro, Y. Wakiyama, and T. Mukaiyama, Chem. Lett.,
1998, 567.
17 a) E. Mondal, G. Bose, P. R. Sahu, and A. T. Khan, Chem.
Lett., 2001, 1158. b) U. Bora, G. Bose, M. K. Chaudhuri, S. S.
Dhar, R. Gopinath, A. T. Khan, and B. K. Patel, Org. Lett., 2,
247 (2000).
RO
RO
BnO
BnO
g
OH
BnO
BnO
R = -COCH2OPh
R = -COCH2OPh
OAc
OAc
1.25c
6.0c
70
78
O
O
h
BnO
BnO
BnO
BnO
SEt
SEt
OH
OH
BnO
OBz
BnO
OBz
O
O
i
BnO
BnO
BnO
BnO
BnO
BnO
O
O
6.5c
7.0c
75
O
O
j
BnO
BnO
BnO
BnO
SEt
OH
OH
BnO
BnO
OAc
OAc
O
O
73
k
AcO
AcO
BnO
BnO
SEt
BnO
BnO
18 G. E. Meister and A. Butler, Inorg. Chem., 33, 3269 (1994).
19 Method A: To a stirred solution of ammonium heptamolyb-
date tetrahydrate (0.124 g, 0.1 mmol) in water (0.5 mL), were
added 30% hydrogen peroxide solution (360 ꢂL, 3.2mmol)
and perchloric acid (0.1 mmol, 9 ꢂL) at ice-bath temperature
and stirring was continued. After 20 min, ammonium bromide
(0.074 g, 0.75 mmol) was added in portion and immediately
the colour changed into deep yellow from light pale yellow.
Then, the substrate ethyl 2,3,4,6-tetra-O-acetyl-1-thio-ꢁ-D-
glucopyranoside (1a) (0.098 g, 0.25 mmol) was added by
dissolving in dichloromethane (2mL) to the above solution.
The reaction was completed within a 3.5 h as monitored by
TLC. The reaction mixture was finally extracted with CH2Cl2
(10 mL ꢂ 2) and the organic layers were dried over anhydrous
Na2SO4. The organic extract was concentrated in vacuo to
give the crude product, which was finally purified by column
chromatography on silica gel (eluent: hexane/EtOAc, 1 : 1).
The pure product 2,3,4,6-tetra-O-acetyl-D-glucopyranose
(2a) was obtained 0.071 g (82%). Method B: The compound
2a was also prepared from 1a using molybdic acid following
the identical procedure as above.
a
Products have been characterized by 1H-NMR, 13C-NMR, mass spectra, elemental
b
analyses, and specific rotation. Isolated yield. cMethod A. dMethod B.
hydroxy sugar chemoselectively by using ammonium bromide,
ammonium heptamolybdate or molybdic acid, H2O2 and
perchloric acid under very mild conditions. It is interesting to
note that neither olefinic double bond nor anomeric position was
brominated under the experimental conditions. Due to its
operational simplicity, generality, efficacy, and cost effective-
ness, this method is expected to have much wider applicability for
the hydrolysis of thioglycosides. Other thioglycosides can also be
hydrolyzed using other alkali metal bromides under similar
reaction conditions, which are under investigation.
A. T. K. acknowledges the Council of Scientific and
Industrial Research, New Delhi for financial support (Grant
No.: 01(1541)/98/EMR-II). B. M and G. B. are thankful to the
CSIR for their research fellowships. The authors are also thankful
to the Director, I. I. T. Guwahati for providing general facilities
for this work.
References and Notes
1 K. Kunz, Angew. Chem., Int. Ed. Engl., 26, 294 (1987).
2R. R. Schmidt, Pure Appl. Chem., 61, 1257 (1989).
20 G. A. Olah, S. C. Narang, and G. F. Salen, Synthesis, 1980,
657.