The trityl tetrakis(pentafluorophenyl)borate catalyzed stereoselective glycosylation using new glycosyldonor, 3,4,6-Tri-O-benzyl-2-O-p-toluoyl-β-D-glucopyranosyl phenylcarbonate

Article abstract of DOI:10.1246/cl.2000.122

The trityl tetrakis(pentafluorophenyl)borate [TrB(C₆F₅)₄] catalyzed stereoselective synthesis of various disaccharides was successfully carried out by treating a new 2-O-acyl-protected glycosyl donor, 3,4,6-tri-O-benzyl-2-O-p-toluoyl-β-D-glucopyranosyl phenylcarbonate, with several glycosyl acceptors, thioglycosides, affording the corresponding disaccharides in high yields.

Full text of DOI:10.1246/cl.2000.122

122
Chemistry Letters 2000
The Trityl Tetrakis(pentafluorophenyl)borate Catalyzed Stereoselective Glycosylation Using
New Glycosyldonor, 3,4,6-Tri-O-benzyl-2-O-p-toluoyl-β-D-glucopyranosyl Phenylcarbonate
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 18,1999;CL-990894)
required careful examinations since this thioglycoside is not so
reactive as a glycosyl donor. It was observed that the use of
pivalonitrile as solvent was essential to the promotion of the
reaction and that the reaction did not take place under the reac-
tion temperature below 0 °C while the above reaction smooth-
ly proceeded at room temperature when both donors and
acceptors were monosaccharides (Scheme 1. below). As
shown in Scheme 2, the one-pot sequential reactions under the
The trityl tetrakis(pentafluorophenyl)borate [TrB(C6F5)4]
catalyzed stereoselective synthesis of various disaccharides
was successfully carried out by treating a new 2-O-acyl-pro-
tected glycosyl donor, 3,4,6-tri-O-benzyl-2-O-p-toluoyl-β-D-
glucopyranosyl phenylcarbonate, with several glycosyl accep-
tors, thioglycosides, affording the corresponding disaccharides
in high yields.
Development of a convenient method for preparation of
complex oligosaccharides is still a significant challenging topic
in the field of synthetic organic chemistry. After 1990’s, a
considerable progress has been made in the one-pot sequential
glycosylation reaction to achieve the rapid synthesis of
oligosaccharides.1 In our previous paper,2 a one-pot synthesis
of trisaccharides by the combination of two types of
TrB(C6F5)4–catalyzed glycosylation reactions to form trisac-
charide composed of three glucoses, Glcβ1-6Glcβ1-6Glc, was
reported. In continuation to the above experiment, further
study on several glycosylation reactions aiming to the one-pot
synthesis of more complex saccharide chains was tried herein.
In recent years, preparation of oligosaccharides containing
a variety of 2-amino-2-deoxy sugars3 attracted great attention
to understanding the biological activities of the glycoproteins,
glycolipids, and other glycoconjugates. In order to accomplish
the one-pot sequential synthesis of trisaccharides containing 2-
amino-2-deoxy sugar as a component, the prepararion of disac-
charides composed of 2-N-phthaloyl protected thioglycoside
was studied first.
above mentioned conditions, however, gave the desired trisac-
charide in poor yield, unexpectedly. By identifying by-prod-
ucts, it was further revealed that the glycosidic bond of the di-
saccharide 2 was cleaved by TrB(C6F5)4 during the second
glycosylation step. Consequently, further improvement of the
two coupling reactions was studied thoroughly to complete the
desired one-pot trisaccharide formation. In this communica-
tion, we would like to report detailed conditions of glycosyla-
tion using glycosyl phenylcarbonates, which is the first step of
the one-pot sequential glycosylation.
The tuning of the protecting groups of glycosyl phenyl-
carbonate was examined in order to enhance the stability of
glycosidic bond. When 2,3,4,6-tetra-O-benzoyl glucosyl
phenylcarbonate was used in the TrB(C6F5)4–catalyzed glyco-
sylation reaction, the reactivity of the donor decreased dramat-
ically compared to that of p-chlorobenzyl protected glycosyl
phenylcarbonate (Table 1). Actually, no reaction took place
under low temperatures ranging from -40 ˚C ~ 0 ˚C when gly-
cosylation of 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl
phenylcarbonate with methyl 2,3,4-tri-O-benzoyl-α-D-glu-
copyranoside (3) was tried in the presence of 30 mol% of
TrB(C6F5)4. The reaction began very slowly at 0 °C and final-
In the first place, optimizations of reaction conditions of
the above two glycosylation steps were investigated to under-
stand the effects of protecting groups of glycosyl donor and of
activators (Scheme 1). p-Chlorobenzyl protected glycosyl
phenylcarbonate reacted with 2-N-phthaloyl protected thiogly-
coside (1) in mixed solvent containing pivalonitrile in the pres-
ence of 10 mol% of TrB(C6F5)4 to afford the desired disaccha-
ride (2) in 88% yield with high stereoselectivity (α/β=4/96).
On the other hand, application of TrB(C6F5)4–NaIO4 system4
for the activation of 2-N-phthaloyl protected thioglycoside cor-
responding to the second step of the one-pot glycosylation
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
123
ly, it proceeded smoothly at room temperature and afforded the
corresponding disaccharide in 80% yield. On the other hand,
the desired disaccharide was not formed in the case of glycosy-
lation using an inactive glycosyl acceptor, ethyl 3-O-acetyl-6-
O-benzyl- 2-N-phthaloyl-2-deoxy-1-thio-β-D-glucopyranoside
(4) since the cleavage of the anomeric ethylthio group took
place prior to the coupling reaction (Table 1. Entry 3).
tive glycosylation because of its high reactivity and its high
stereoselectivity.
Further study on the application of this glycosylation
method to a one-pot sequential glycosylation will be reported
in the paper to follow.
The typical experimental procedure 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 a solution (pivalonitrile:dichloromethane=2:1, 0.8 ml) of
5 (41.3 mg, 0.06 mmol) and 1 (24.3 mg, 0.05 mmol) at -20 °C.
After the reaction mixture was stirred for 6 h at -20 °C, 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 brine (5 ml) and the organic
layer was dried over Na2SO4. After filtration and evaporation,
the resulting residue was purified by preparative TLC (silica
gel) to give the desired product (47.0 mg, 91%).
In order to accomplish a successful preparative method for
various oligosaccharides, enhancement of reactivities of glyco-
syl donors is always required. S. V. Ley reported5 the precise
data on the reactivity of rhamnose and mannose derivatives
and revealed that the 3-, 4-, and 6-benzoyl protecting groups
showed significant deactivation compared with benzyl protect-
ed ones. They concluded that, except for the neighboring C-2
substituent, proximity of electron withdrowing protecting
groups to the ring oxygen was more influential compared with
their distance from the anomeric position. Then, it was
planned to prepare a modified glycosyl donor in which only C-
2 hydroxy group was protected by benzoyl (Bz) group and
other hydroxy groups were protected by benzyl (Bn) group.6
As summarized in Table 2, reactivity of the modified glycosyl
donor was dramatically improved compared with that of per-
benzoylated one. The new glycoyl donor, 3,4,6-tri-O-benzyl-
2-O-p-toluoyl-β-D-glucosyl phenylcarbonate7 (5), reacted
smoothly with 3 in the presence of a catalytic amount of
TrB(C6F5)4 at -15 ˚C to afford the corresponding disaccharide
stereoselectively in high yield (Entry 1). 2-N-Phthaloyl pro-
tected or 2-O-benzoyl protected ethyl thioglycosides having 6-
OH group reacted with 5 at -20 °C to yield the desired prod-
ucts in high yields. However, the glycosylation using an inac-
tive acceptor (4) did not give a satisfactory result since the
cleavage of the anomeric ethylthio group took place prior to
the coupling reaction (Table 2. Entry 5). It had already been
known in our laboratory that the use of pivalonitrile as solvent
quite smoothly promoted replacement of the leaving group
with an acceptor and also the cleavage of glycosidic linkage.8
Then, the reaction was next examined in dichloromethane
alone and much improvement was observed concerning chemi-
cal yield though the reaction time became longer (Entry 3, 7).
Thus, catalytic and stereoselective syntheses of various
disaccharides by using a 2-O-acyl-protected glycosyl donor,
3,4,6-tri-O-benzyl-2-O-p-toluoyl-β-D-glucosyl phenylcarbon-
ate, was successfully developed. It is noted that 2-O-acyl-pro-
tected glycosyl donor was suitable for the catalytic stereoselec-
The present research is partially supported by Grant-in-
Aids for Scientific Research from Ministry of Education,
Science, Sports and Culture.
References and Notes
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7
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The donor 5 was prepared from 3,4,6-tri-O-benzyl glucose9
according to the following equation. 2-O-Benzoyl and 2-O-p-
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a) p-Toluoyl chloride, DMAP / pyridine / 0 °C ~ rt / 89%, b)
CH3(CH2)11SH, BF3•OEt2 / CH2Cl2 / 0 °C ~ rt / 78%, c) 30 mol%
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8
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