Mild and efficient hydrolysis of thioglycosides to glycosyl hemiacetals using N-iodosaccharin

Article abstract of DOI:10.1055/s-2007-977412

A convenient methodology has been developed for the mild hydrolysis of thioglycosides to the corresponding hemiacetals using N-iodosaccharin without any requirement of co-activator. Most of the functional groups used for the protecting group manipulation of carbohydrates remain unaffected under the reaction conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-977412

LETTER
1207
Mild and Efficient Hydrolysis of Thioglycosides to Glycosyl Hemiacetals Using
N-Iodosaccharin1
Hydrolysis of
i
T
hiogl
n
G
t
lycosy
u
l
H
emiacetals
U
sin
K
g
N
-Iodosaccharinumar Mandal, Anup Kumar Misra*
Medicinal and Process Chemistry Division, Central Drug Research Institute, Chattar Manzil Palace, Lucknow 226001, UP, India
Fax +91(522)2223938; E-mail: akmisra69@rediffmail.com
Received 29 August 2006
a more potent iodinating agent than NIS and it should
Abstract: A convenient methodology has been developed for the
activate thioglycosides without the requirement of any
strong acid as co-activator. Taking cues from the literature
reports, we have reasoned that NISac could independently
mild hydrolysis of thioglycosides to the corresponding hemiacetals
using N-iodosaccharin without any requirement of co-activator.
Most of the functional groups used for the protecting group
manipulation of carbohydrates remain unaffected under the reaction activate thioglycosides in a moist reaction condition
conditions.
resulting in the formation of hemiacetals. Avoiding the
addition of acidic co-activator could make this method
equally effective for hydrolyzing thioglycosides having
both acid-labile as well as base-labile protecting groups.
N-Iodosaccharin can be easily prepared25 in the laboratory
and it is very much cost-effective in comparison to analo-
gous N-iodosuccinimide (NIS).
Key words: carbohydrate, hydrolysis, thioglycoside, hemiacetals,
N-iodosaccharin
Suitably functionalized glycosyl hemiacetals are useful
intermediates for the preparation of various glycosyl
donors used in the synthesis of oligosaccharides.2–4 They
can be converted into more reactive glycosyl donors such
as glycosyl fluorides,5 trichloroacetimidates6 and as such
can be used in dehydrative glycosylation reactions.7 They
have also been applied in Wittig or Horner–Emmons or
related reactions for chiral synthesis of various natural
products.8,9 Glycosyl hemiacetals can be prepared from
(a) peracetylated sugars using hazardous hydrazine salts10
OR
OR
O
NISac
O
RO
RO
RO
RO
SR1
OH
RO
MeCN–H2O (10:1), r.t.
RO
R
1 = Et, Ph, Tol
Scheme 1
or organic bases like benzyl amine11 or under acidic con- In an initial set of experiments, ethyl 2,3,4,6-tetra-O-
ditions;12 (b) acid hydrolysis of alkyl glycosides;13 or (c) acetyl-1-thio-b-D-glucopyranoside was treated with 1.5
hydrolysis of thioglycosides. Among them, hydrolysis of equivalents of NISac in wet acetonitrile (MeCN–H2O =
thioglycosides is more useful as it provides the prepara- 10:1) at room temperature (Scheme 1). To our satisfac-
tion of glycosyl hemiacetals having diverse functional- tion, a clean formation of glycosyl hemiacetal was
ities under mild reaction conditions. As expected, a achieved in almost quantitative yield in only five minutes.
number of reports appeared in the literature for this Reducing the quantity of NISac resulted in incomplete
purpose, including the use of toxic heavy metal salts,14 N- hydrolysis of thioglycoside even after 24 hours. Similar
bromosuccinimide (NBS)15 or N-iodosuccinimide (NIS) reaction conditions were then applied to hydrolyze a
alone16 or in the presence of an acid,17–19 borate salts/n- diverse set of thioglycosides containing base-labile and
Bu4NIO4/HClO4,20 V2O5/H2O2/NH4Br,21 (NH4)6Mo7O24/ acid-labile functional groups, which is presented in
H2O2HClO4/NH4Br,22 and chloramine-T.23 However, Table 1. In Table 1, there are a number of points that need
many of these methods suffer from limitations, such as to be highlighted. All reactions were complete in 5–30
use of expensive reagents, incompatibility with acidic minutes. The reaction condition is compatible with the
functional groups, relatively low yield and sometime acid-labile functional groups (benzylidene, isopropyl-
harsh reaction conditions. In search of a generalized reac- idene, silyl ether, 4-methoxybenzylidene) as well as base-
tion condition for the hydrolysis of thioglycosides having labile groups (acetyl, benzoyl, chloroacetyl). Interglyco-
acid-labile and base-labile functional groups, we have sidic linkage remains unaffected under the reaction condi-
tested the efficacy of N-iodosaccharin (NISac) for this tion. The rate of activation depends on the alkyl or aryl
purpose. Recently, NISac has been used in the glycosyla- part linked to the sulfur atom; thus the SPh group takes a
tion reaction using armed glycosyl donors24 and iodina- longer time to hydrolyze than the SEt or STol glycosides.
tion of alkenes25 and conversion of alcohols to iodides.26 The rate of hydrolysis for the acyl-protected thio-
As discussed earlier,24 due to the lower pKa value of NISac glycosides is slightly slower than the alkyl-protected
(pKa 1.30) than its analogous NIS (pKa 9.62), it should be counterpart, which may be explained by considering the
‘armed-disarmed’ concept. In most of the cases, an ano-
meric mixture of glycosyl hemiacetals was formed and the
SYNLETT 2007, No. 8, pp 1207–1210
Advanced online publication: 03.04.2007
DOI: 10.1055/s-2007-977412; Art ID: D25606ST
© Georg Thieme Verlag Stuttgart · New York
1
6.
0
5.
2
0
0
7
ratio was determined from the 1H NMR of the crude prod-
ucts. A series of solvents has been tested for the reaction

1208
P. K. Mandal, A. K. Misra
LETTER
and MeCN–H2O (10:1) mixture has been found to be the glycosides without requirement of any co-activator. Most
best option in comparison to other commonly used sol- of the functional groups used for the protecting group ma-
vents like dichloromethane and THF. In contrast to the nipulation of carbohydrate were found unaffected under
earlier report,24 no trace of formation of glycosyl saccha- the reaction condition. It is important to mention that N-
rine derivatives was observed. The formation of the iodosaccharine (NISac) is very cheap in comparison to its
product could be explained by considering the formation closest analogue, N-iodosuccinimide (NIS). Straightfor-
of sulfonium ion generated by NISac activation of ward operation, low-cost activator, very short reaction
thioglycoside followed by hydrolysis.
time, and simple purification of products are the key fea-
tures of this generalized protocol, which makes it an
attractive alternative to the existing literature procedures.
In summary, a relative shortcoming of the hydrolysis of
thioglycosides has been overcome by devising a general-
ized, mild reaction protocol for the hydrolysis of thio-
Table 1 Hydrolysis of Thioglycosides Using N-Iodosaccharin (NISac) at Room Temperature27
Entry
1
Thioglycosides 1a
Products 2a
Time (min)
5
Yield (%)
95
a/b
Ref.
21
OAc
OAc
O
3:1
O
AcO
AcO
AcO
AcO
SEt
OH
AcO
AcO
OAc
OAc
O
2
3
4
20
5
92
95
92
3.5:1
3:1
21
21
21
O
AcO
AcO
AcO
AcO
SPh
STol
AcO
AcO
OH
OH
OAc
O
OAc
O
AcO
AcO
AcO
AcO
AcO
AcO
OAc
OAc
AcO
AcO
AcO
O
5
2.5:1
O
STol
AcO
AcO
AcO
OH
AcO
AcO
AcO
OAc
O
AcO
AcO
AcO
OAc
O
5
20
90
1:0
21
OH
SPh
OBz
OBz
BzO
BzO
BzO
BzO
6
7
8
9
5
3
3
5
92
88
85
95
3:1
21
23
21
21
O
O
SEt
BzO
BzO
OH
OBn
O
OBn
O
2:1
BnO
BnO
BnO
SEt
BnO
BnO
BnO
OH
OH
OBn
OBn
CAO
CAO
CAO
CAO
3:1
O
O
SEt
OBn
OBn
OTBDPS
O
OTBDPS
O
2.5:1
BzO
BzO
BzO
BzO
SEt
OH
OBz
OBz
SEt
OH
Me
O
10
5
92
4:1
12
Me
O
AcO
AcO
AcO
AcO
OAc
OAc
SPh
OH
Me
BnO
Ph
O
11
12
3
90
90
5:1
1:1
21
21
Me
O
OBn
OBn
OBn
OBn
BnO
Ph
O
O
BzO
O
O
BzO
O
O
30
SPh
BzO
BzO
OH
Synlett 2007, No. 8, 1207–1210 © Thieme Stuttgart · New York

LETTER
Thioglycosides to Glycosyl Hemiacetals Using N-Iodosaccharin
1209
Table 1 Hydrolysis of Thioglycosides Using N-Iodosaccharin (NISac) at Room Temperature27 (continued)
Entry
13
Thioglycosides 1a
Products 2a
Time (min)
20
Yield (%)
90
a/b
Ref.
Ph
O
Ph
O
O
O
O
O
AcO
1:2
–
OH
SPh
NPhth
AcO
NPhth
PhOMe
PhOMe
O
O
O
O
14
15
20
5
85
92
2:1
3:1
23
O
O
SPh
SEt
BnO
BnO
BnO
OH
OH
BnO
Me
AcO
O
O
Me
AcO
O
23
O
O
O
SPh
OH
O
O
OBz
OBz
16
17
18
10
5
82
80
95
5:1
2:1
2:1
21
21
21
OBz
OBz
OBz
OBz
OBz
OBz
OBn
OBn
AllO
AllO
O
O
STol
MBnO
MBnO
OH
OBn
OBn
OAc
O
OAc
AcO
AcO
AcO
AcO
OAc
O
OAc
O
O
5
O
O
STol
STol
AcO
AcO
AcO
AcO
AcO
AcO
OH
OH
OAc
OAc
O
O
AcO
AcO
AcO
AcO
19
20
5
95
2:1
–
21
–
OAc
O
OAc
O
AcO
AcO
O
O
AcO
AcO
AcO
AcO
OAc
AcO
AcO
OAc
AcO
AcO
20
80b
CH(SEt)2
OAc
CHO
OAc
AcO
AcO
a Tol = tolyl; CA = chloroacetyl; Phth = phthalimido; MBn = 4-Methoxybenzyl.
b NISac (2.5 equiv) was used.
(8) Hanessian, S. In Total Synthesis of Natural Products: The
Chiron Approach; Baldwin, J. E., Ed.; Pergamon: Oxford,
1983.
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1975, 39, 368.
Acknowledgment
Instrumentation facilities from SAIF, CDRI are gratefully acknow-
ledged. P.K.M. thanks CSIR, New Delhi for providing Junior Rese-
arch Fellowship. This project was partly funded by the Department
of Science and Technology (DST), New Delhi, India.
(11) Conchie, J.; Levvy, G. A. Meth. Carbohydr. Chem. 1963, 2,
345.
(12) Tiwari, P.; Misra, A. K. Tetrahedron Lett. 2006, 47, 3573.
(13) Koto, S.; Morishima, N.; Miyata, Y.; Zen, S. Bull. Chem.
Soc. Jpn. 1976, 49, 2639.
(14) Ogawa, T.; Koike, K.; Numata, M.; Sugimoto, M.;
Nakahara, M. Jpn. Patent, JP 8835591, 1988.
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Chem. 1995, 14, 1279.
References and Notes
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1043.
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Takao, K.; Kobayashi, S. Tetrahedron 1997, 53, 10993.
(17) Duynstee, H. I.; de Koning, M. C.; Ovaa, H.; van der Marel,
G. A.; van Boom, J. H. Eur. J. Org. Chem. 1999, 2623.
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H. S.; van der Marel, G. A. Carbohydr. Res. 2006, 341,
1723.
(5) Caputo, R.; Kunz, H.; Mastroianni, D.; Palumbo, G.;
Pedatella, S.; Solla, F. Eur. J. Org. Chem. 1999, 3147.
(6) Schmidt, R. R.; Jung, K.-H. In Preparative Carbohydrate
Chemistry; Hanessian, S., Ed.; Marcel Dekker: New York,
1996, 283–312.
(7) (a) Nguyen, H. M.; Poole, J. L.; Gin, D. Y. Angew. Chem.
Int. Ed. 2001, 40, 414. (b) Garcia, B. A.; Gin, D. Y. Org.
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(19) Dasgupta, S.; Roy, B.; Mukhopadhyay, B. Carbohydr. Res.
2006, 341, 2708.
Synlett 2007, No. 8, 1207–1210 © Thieme Stuttgart · New York

1210
P. K. Mandal, A. K. Misra
LETTER
to furnish the pure glycosyl hemiacetal as an anomeric
mixture. Products of all known compounds gave acceptable
1H NMR and 13C NMR spectra that matched the data
reported in the cited references.28
(20) Uchiro, H.; Wakiyama, Y.; Mukaiyama, T. Chem. Lett.
1998, 567.
(21) Bujar Barua, P. M.; Sahu, P. R.; Mondal, E.; Bose, G.; Khan,
A. T. Synlett 2002, 81.
(22) Mondal, E.; Bujar Barua, P. M.; Bose, G.; Khan, A. T.
Chem. Lett. 2002, 210.
(23) Misra, A. K.; Agnihotri, G. Carbohydr. Res. 2004, 339, 885.
(24) (a) Aloui, M.; Fairbanks, A. J. Synlett 2001, 797. (b) Aloui,
M.; Fairbanks, A. J. Chem. Commun. 2001, 1406.
(25) Dolenc, D. Synlett 2000, 544.
(28) Spectral data of selected compounds:
3-O-Acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-D-
glucopyranose (Table 1, Entry 13): 1H NMR (300 MHz,
CDCl3): d = 7.33–7.91 (m, 9 H, aromatic protons), 5.85 (t,
J = 9.0 Hz, 1 H, H-3), 5.69 (d, J = 8.1 Hz, 1 H, H-1), 5.58 (s,
1 H, PhCH), 4.48 (dd, J = 4.5, 10.2 Hz, 1 H, H-4), 4.35–4.40
(m, 1 H, H-2), 3.70–3.83 (m, 3 H, H-5, H-6a, H-6b), 1.88 (s,
3 H, OCOMe). ESI-MS: m/z calcd for C23H21NO8: 439;
found: 462 [M + Na]+.
2,3,4,5,6-Penta-O-acetyl-D-galactose (Table 1, Entry 20):
1H NMR (300 MHz, CDCl3): d = 2.04–2.12 (5 × s, 15 H),
3.91 (dd, 1 H), 4.26 (dd, 1 H), 5.26 (d, J = 2.0 Hz, 1 H), 5.36
(m, 1 H), 5.49 (d, J = 8.0 Hz, 1 H), 5.62 (d, J = 8.0 Hz, 1 H),
9.45 (br s, 1 H). ESI-MS: m/z calcd for C16H22O11: 390;
found: 413 [M + Na]+.
(26) Firouzabadi, H.; Iranpoor, N.; Ebrahimzadeh, F.
Tetrahedron Lett. 2006, 47, 1771.
(27) Typical Experimental Procedure: To a solution of
thioglycoside (1.0 mmol) in MeCN–H2O (10:1; 5 mL) was
added N-iodosaccharin (1.5 mmol) at r.t. and the reaction
mixture was allowed to stir for the time mentioned in
Table 1. After completion of the reaction, the reaction
mixture was concentrated under reduced pressure. The crude
mass was purified over SiO2 using hexane–EtOAc as eluent
Synlett 2007, No. 8, 1207–1210 © Thieme Stuttgart · New York

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