Stereoselective glycosylation of thioglycosides promoted by respective combinations of N-Iodo-or N-Bromosuccinimide and trityl tetrakis(pentafluorophenyl)borate. Application to one-pot sequential synthesis of trisaccharide

Article abstract of DOI:10.1246/cl.2000.124

New highly effective promoter system for the glycosylation of thioglycoside, the combined use of stoichiometric amount of either N-iodosuccinimide or N-bromosuccinimide and a catalytic amount of TrB(C₆F₅)₄, was developed and was successfully applied to the one-pot sequential synthesis of trisaccharides. In the first glycosylation step, 3,4,6-tri-O-benzyl-2-O-p-toluoyl-β-D-glucopyranosyl phenylcarbonate was treated with thioglycosides in the presence of a catalytic amount of TrB(C₆F₅)₄ alone, and the following glycosylation with methyl α-D-glycosides was carried out by further addition of either N-iodosuccinimide or N-bromosuccinimide to the initially resulted reaction mixture to afford the corresponding trisaccharides in one-pot manner.

Full text of DOI:10.1246/cl.2000.124

124
Chemistry Letters 2000
Stereoselective Glycosylation of Thioglycosides Promoted by Respective Combinations of
N-Iodo- or N-Bromosuccinimide and Trityl Tetrakis(pentafluorophenyl)borate.
Application to One-Pot Sequential Synthesis of Trisaccharide
Kazuya Takeuchi, Takayuki Tamura, and Teruaki Mukaiyama
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received October 20, 1999;CL-990897)
New highly effective promoter system for the glycosyla-
tion of thioglycoside, the combined use of stoichiometric
amount of either N-iodosuccinimide or N-bromosuccinimide
and a catalytic amount of TrB(C6F5)4, was developed and was
successfully applied to the one-pot sequential synthesis of
trisaccharides. In the first glycosylation step, 3,4,6-tri-O-ben-
zyl-2-O-p-toluoyl-β-D-glucopyranosyl phenylcarbonate was
treated with thioglycosides in the presence of a catalytic
amount of TrB(C6F5)4 alone, and the following glycosylation
with methyl α-D-glycosides was carried out by further addition
of either N-iodosuccinimide or N-bromosuccinimide to the ini-
tially resulted reaction mixture to afford the corresponding
trisaccharides in one-pot manner.
Developments in new strategies and tactics of oligosaccha-
ride synthesis are of growing importance and many examples
are reported; for example, armed–disarmed, two-stage activa-
tion, active–latent, orthogonal, one-pot multistep and solid-
phase glycosylation reactions and so on.1 A one-pot sequential
glycosylation method2 is among the most promising strategies
for the synthesis of polysaccharides because of its simplicity in
preparing saccharide blocks.
high yield as was shown in the preceding paper.4 Then the
second glycosylation was carried out by adding NaIO4 and gly-
cosyl acceptor to the reaction mixture. However, the desired
trisaccharide was obtained in only 21% yield since cleavege of
the initially formed glycosidic bond occurred during the sec-
ond glycosylation step at room temperature. In order to over-
come these problems, the development of more effective
method for glycosylation of thioglycosides was studied and the
combined use of N-iodosuccinimide (NIS) and TrB(C6F5)4
gave satisfactory results. The NIS–triflic acid system5 was
well known to activate thioglycosides effectively. After that,
several Lewis acids such as Et3SiOTf or AgOTf were used6
together with NIS as promoters. It was assumed that I+-
In our previous paper,3 a one-pot synthesis of trisaccharides
by the combination of two types of TrB(C6F5)4–catalyzed glyco-
sylation reactions to form trisaccharide composed of three glu-
coses, Glcβ1-6Glcβ1-6Glc, was reported. In the preceding com-
munication,4 detailed conditions for glycosylation reaction using
glycosyl phenylcarbonate were presented and now we would like
to report the improved one-pot sequential glycosylation reactions
of forming various trisaccharides including those containing 2-
amino-2-deoxy sugar by promotion of TrB(C6F5)4 catalyst.
-
B(C6F5)4 , highly thiophilic iodonium cation, was generated in
situ by combined use of NIS and TrB(C6F5)4. In the present
experiment, it was shown that the glycosylation proceeded
very rapidly even at -15 °C by using a combination of NIS and
TrB(C6F5)4 to give the desired glycoside in high yield as
shown in Table 1 (Entry 1,3,5,7). In addition, it was observed
that the above reaction was also promoted by using N-bromo-
succinimide (NBS), a cheaper and stabler compound than NIS.
Actually, the NBS-TrB(C6F5)4 system turned out quite effec-
tive to afford several disaccharides in good to high yields as
shown in Table 1 (Entry 2,4,6,8).7
Finally, the improved one-pot sequential glycosylation
was tried based on the above experiments. In the first step, 1
was treated with ethyl thioglycosides (2, 7, 8) in the presence
of a catalytic amount of TrB(C6F5)4 alone, and almost com-
plete consumption of thioglycosides was confirmed by TLC
In the first place, the one-pot sequential glycosylation was
attempted according to the reactions shown in Scheme 1. 2-O-
p-Toluoyl protected glucosyl phenylcarbonate (1) reacted with
thioglycoside (2) to afford the corresponding disaccharide in
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
125
Thus, an improved one-pot sequential glycosylation reac-
tion was successfully carried out by using a catalytic amount of
TrB(C6F5)4 and a variety of trisaccharides including those contain-
ing 2-amino-2-deoxy sugars were stereoselectively synthesized.8
The typical experimental procedure of the one-pot sequen-
tial glycosylation is as follows: to a stirred suspension of trityl
tetrakis(pentafluorophenyl)borate (4.6 mg, 0.005 mmol) and
Drierite (250 mg) in a mixed solvent (pivalonitrile:
dichloromethane=2:1, 0.45 ml) was successively added the
solution (pivalonitrile:dichloromethane=2:1, 0.8 ml) of 1 (41.3
mg, 0.06 mmol) and 2 (24.3 mg, 0.05 mmol) at -20 °C. After
the reaction mixture was stirred for 6 h at -20 °C, 5 (42.5 mg,
0.075 mmol) in dichloromethane (0.75 ml) and NIS (16.9 mg,
0.075 mmol) were successively added at -20 °C. The reaction
mixture was stirred for additional 1 h at -20 °C and then it was
quenched by adding saturated aqueous NaHCO3 (10 ml). The
mixture was filtered through Celite and extracted with
dichloromethane (3 times, each of 20 ml). The combined
organic layer was washed with 10% aqueous Na2S2O3 (5 ml),
water (5 ml) and brine (5 ml). Then, the organic layer was
dried over Na2SO4. After filtration and evaporation, the result-
ing residue was purified by preparative TLC (silica gel) to give
the desired product 10 (61.5 mg, 83%).
Further study on preparation of naturally occurring
oligosaccharides by this glycosylation method is now in
progress.
The present research is partially supported by Grant-in-
Aids for Scientific Research from Ministry of Education,
Science, Sports and Culture.
References and Notes
1
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2
S. Raghavan and D. Kahne, J. Am. Chem. Soc., 115, 1580 (1993);
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Hinzen, S. J. Ince, P. Langer, S. V. Ley, and S. L. Warriner,
Synlett, 1998, 440; S. V. Ley and H. W. M. Priepke, Angew.
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3
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monitoring. Next, the second glycosylations of thus formed
disaccharides with several methyl α-glucosides (5, 6, 9)
afforded the corresponding trisaccharides in good to high
yields by further addition of 150 mol% of NIS to the reaction
mixture. In a similar manner, the desired trisaccharides were
also obtained when the same amount of NBS instead of NIS
was used in the above experiments (Table 2. Entry 4,5,6). In
the case of using glucosides having a C-3 or C-4 hydroxy
group as acceptors, the yields of trisaccharides decreased and
the 1-hydroxy disaccharides were isolated after quenching.
When 5.0 eq. of glycosyl acceptor (C) was used in the above
experiments, total yields of trisaccharides were much
improved. (Table 2. Entry 2,3,5,6,8,9,11).
6
7
P. Konradsson, U. E. Udodong, and B. Fraser-Reid, Tetrahedron
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The use of NBS for the activation of thioglycoside has been
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Chem. Soc., 105, 2430 (1983); M. Sasaki, K. Tachibana, and H.
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Kusumoto, Tetrahedron, 51, 4293 (1995).
1
8
The structures of trisaccharides (10~17) are supported by H and
13C NMR (500 MHz) and FAB-MS spectrum. Selected NMR
data of 13: 1H NMR (500 MHz, CDCl3) 4.68 (d, 1H, H-1", J1", 2"
=
7.94 Hz), 4.70 (d, 1H, H-1', J1',2' = 7.94 Hz), 5.00 (d, 1H, H-1, J1,2
= 3.36 Hz); 13C NMR (500 MHz, CDCl3) 96.5 (C-1), 101.1 (C-1'),
101.1 (C-1").