Glycosyl 6-nitro-2-benzothiazoate. A highly efficient donor for β-stereoselective glycosylation

Article abstract of DOI:10.1246/cl.2003.340

Highly β-stereoselective glycosylations of glycosyl acceptors having a primary hydroxyl group by using a novel glycosyl donor, α-glycosyl 6-nitro-2-benzothiazoate (3), proceeded smoothly in the presence of a catalytic amount of trifluoromethanesulfonic ac

Full text of DOI:10.1246/cl.2003.340

340
Chemistry Letters Vol.32, No.4 (2003)
Glycosyl 6-Nitro-2-benzothiazoate. A Highly Efficient Donor for
ꢀ-Stereoselective Glycosylation
Teruaki Mukaiyama,y;yy Takashi Hashihayata,y;yy and Hiroki Mandaiy;yy
yCenter for Basic Research, The Kitasato Institute (TCI), 6-15-5 Toshima, Kita-ku, Tokyo 114-0003
yyThe Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
(Received January 8, 2003; CL-030026)
Highly ꢀ-stereoselective glycosylations of glycosyl accep-
was noted that a glycosyl donor having nonsubstituted benzo-
thiazole was too labile and was partly hydrolyzed during the
work-up procedure. This result indicated that it was the nitro
group, an electron-withdrawing substituent, that contributed to
the increase in stability of 3.
tors having a primary hydroxyl group by using a novel glycosyl
donor, ꢁ-glycosyl 6-nitro-2-benzothiazoate (3), proceeded
smoothly in the presence of a catalytic amount of trifluorometh-
anesulfonic acid (TfOH) in CH2Cl2 at À78 ꢀC to afford the
corresponding glycosides in high yields. The donor 3 gave ꢀ-
saccharides more dominantly compared with those using other ꢁ-
glycosyl donors such as thioform- and trichloroacet-imidates or
fluoride under the same conditions.
Table 1. Glycosylation using various donors using TfOH as a
catalyst
BnO
O
BnO
BnO
BnO
BnO
BnO
BnO
O
TfOH (5 mol%)
MS 5A (3 g/mmol)
R
To develop a new method for stereoselective glycosylation is
one of the most important and fundamental topics in carbohydrate
chemistry.1 Various combinations of glycosyl donors and
activators have been studied during past two decades, which
were successfully applied to the syntheses of various saccharides.
Recently, glycosyl p-trifluoromethylbenzylthio-p-trifluorome-
thylphenyl formimidate was newly reported from our
laboratory.2{4 The above donor, purified easily by recrystalliza-
tion, led catalytic and highly stereoselective glycosylation to
proceed quite smoothly to give either ꢁ- or ꢀ-saccharides in high
yields by choosing suitable solvents and counter anions of the
catalysts. Continuously, development of a newer donor having a
characteristically similar leaving group, glycosyl 6-nitro-2-
benzothiazoate (3), was planned. Since a readily available
glycosyl benzothiazoate contains a moiety [–O–C(=NR1)–SR2]
which is activated easily by Lewis or protic acids, 3 was expected
to behave as a useful donor in the glycosylation. In this
communication, we would like to report on an efficient ꢀ-
stereoselective glycosylation5 with the glycopyranosyl donor 3
using trifluoromethanesulfonic acid (TfOH) catalyst.1{4;6
Donor (1.1 equiv.)
BnO
O
O
HO
CH2Cl2
O
BnO
BnO
BnO
BnO
+
1.0 h
BnO
OMe
BnO
OMe
5
Acceptor 4 (1.0 equiv.)
a
Entry
Donor (R)
Temp. / °C
Yield /% (α/β )
N
O
97 (31/69)
91 (4/96)
1
2
0
S
NO
2
3
6
−78
NH
99 (56/44)
98 (8/92)
0
3
4
O
CCl
3
−78
NPh-pCF
5b
6b
3
98 (66/34)
97 (43/57)
0
O
SBn-pCF
3
−78
7
96 (57/43 )
7
8
0
F
8
−78
Not detected
aThe
bThese results were previously reported in reference 3.
α/β ratios were determined by HPLC analysis.
BnO
1) 2-Chloro-6-nitrobenzo-
O
BnO
thiazole (2), LHMDS
THF/DMF = 9/1, 0 °C
92% (α/β =88/12)
BnO
BnO
BnO
BnO
O
BnO
O
N
It was generally known that the reactivities and stereoselec-
tivies of glycosylations using conventional donors were influ-
enced considerably by the properties of donors, catalysts and
solvents. In the first place, glycosylation of a glycosyl acceptor 4
with 3 in the presence of 5 mol% of TfOH in CH2Cl2, nonpolar
solvent, was tried under the conditions previously reported3
(Table 1). The glycosylation proceeded smoothly to afford the
corresponding disaccharides 5 in high yield with ꢀ-stereoselec-
tivity (Entry 1, ꢁ=ꢀ ¼ 31=69) at 0 ꢀC. Interestingly, the ꢀ-
stereoselectivity of the present glycosylation was higher com-
pared with that of using a donor 7 which afforded the disaccharide
in moderate ꢁ-stereoselectivity (ꢁ=ꢀ ¼ 66=34) under the same
conditions (Entry 5) shown in our previous report.3 Though the
similar moieties [–O–C(=NR1)–SR2] were involved in the above
two donors, 3 and 7, it was noteworthy that the above two
BnO
OH
S
2) Column purification
1
3
77% (based on 1, α-isomer)
NO
2
Scheme 1. Synthesis of the glycosyl benzothiazoate.
2,3,4,6-Tetra-O-benzyl-ꢁ-D-glucopyranosyl 6-nitro-2-ben-
zothiazoate(3) was easily prepared by a direct condensation
reaction between anomeric hydroxyl group of 2,3,4,6-tetra-O-
benzyl-D-glucopyranoside(1)
and
2-chloro-6-
nitrobenzothiazole(2).7 The reaction smoothly proceeded at
0 ꢀC to give a mixture of glycosyl 6-nitro-2-benzothiazoates in
92% chemical yield (ꢁ=ꢀ ¼ 88=12). Each isomer of ꢁ- or ꢀ-one
was separated and purified by silica gel chromatography and ꢁ-3
was obtained in 77% and ꢀ-one in 7% based on 1 (Scheme 1). It
Copyright ꢀ 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.4 (2003)
341
glycosylations afforded the saccharides with reversed stereose-
lectivities (Entries 1 and 5). The donor 3 also gave the saccharides
in a more highly ꢀ-stereoselective manner than ꢁ-glycosyl
trichloroacetimidate8 (6) did at 0 ꢀC (Entries 1 and 3). The ꢁ-
glycosyl fluoride (8), a less reactive donor compared with the
above imidate donors, reacted with acceptor 4 to afford the
glycosides in moderate ꢁ-stereoselectivity (Entry 7). These
results evidently showed that the glycosylation reaction of ꢁ-3
gave ꢀ-anomer more predominantly than those using 6, 7 and 8
under the above mentioned conditions. On the other hand, the
highest ꢀ-stereoselectivity (ꢁ=ꢀ ¼ 4=96) was also performed
(Entry 2) when the donor 3 was allowed to react at À78 ꢀC.
thio-ꢀ-D-glucopyranoside (10), ethyl 3-O-acetyl-O-4-benzyl-2-
deoxy-2-phthalimido-1-thio-ꢀ-D-glucopyranoside (11) or 2,3,4-
tri-O-benzyl-ꢀ-D-glucopyranosyl fluoride (12) as acceptors gave
good results also without giving any damage to thio- or fluoro-
linkage, respectively (Entries 2, 3 and 4).
The typical experimental procedure is as follows: to a stirred
suspension of MS 5A (150 mg), 3 (39.5 mg, 0.055 mmol) and 4
(23.2 mg, 0.050 mmol) in CH2Cl2 (1.25 mL) was added TfOH
(0.38 mg, 2.5 mmol) in toluene (0.05 mL) at À78 ꢀC. After the
reaction mixture was stirred for 1 h at the same temperature, it was
quenched by adding saturated NaHCO3. The mixture was filtered
through Celite and extracted with CH2Cl2. The organic layer was
washed with brine, and dried over Na2SO4. After being filtered
and evaporated, the resulting residue was purified by preparative
TLC (silica gel) to give the desired product 5 (44.9 mg, 91%,
ꢁ=ꢀ ¼ 4=96).
Table 2. Glycosylation of various acceptors
Donor 3 (1.1 equiv.)
TfOH (5 mol%)
MS 5A (3 g/mmol)
BnO
+
O
BnO
O
The donor 3 enabled the glycosylation to achieve higher ꢀ-
stereoselectivity in CH2Cl2 than donors 6, 7 or 8 when a catalytic
amount of TfOH was used. These results imply that glycosyl
benzothiazoate has a potent feature of constructing the stereo-
selective ꢀ-saccharide linkage without using the neighboring
effect of O-2-acyl protecting group. Further application of this
glycosyl benzothiazoate donor to other sugars, such as ꢀ-
mannoside and ꢀ-2-deoxy-glycoside,1 is now in progress.
It should be noted, on the other hand, that the highly ꢁ-
stereoselective glycosylation of 4 with 3 at 0 ꢀC can be
successfully carried out to afford 5 in high yield (88%,
ꢁ=ꢀ ¼ 88=12) using a properly selected combination of catalyst
and solvent9 (20 mol% of HClO4 in tBuOMe).
BnO
O
HO
CH2Cl2
BnO
O
X
X
Acceptor (1.0 equiv.)
disaccharide
−78 °C, 1.0 h
a
Acceptor
Entry
1
Yield /% (α/β)
Product
BnO
HO
O
80 (27/73)b, c
98 (9/91)
13
BnO
BnO
OMe
9
HO
BzO
O
2
3
4
SEt
14
15
BzO
BzO
O
10
HO
BnO
90 (9/91)
SEt
AcO
NPhth
11
This study was supported in part by the Grant of the 21st
Century COE Program from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan.
HO
BnO
O
89 (7/93)d
16
F
BnO
BnO
12
aThe
bThe reaction was carried out for 4 h.
c13 was obtained in 56% yield (
= 50/50) when 6 was used instead of 3.
dThe
ratio was determined by isolated yields of both isomers.
α /β ratios were determined by HPLC analysis.
References and Notes
1
Reviews: K. Toshima and K. Tatsuta, Chem. Rev., 93, 1503
(1993); K. Suzuki and T. Nagasawa, J. Synth. Org. Chem.
Jpn., 50, 378 (1992).
α/β
α /β
2
3
T. Mukaiyama, H. Chiba, and S. Funasaka, Chem. Lett., 2002,
392.
H. Chiba, S. Funasaka, K. Kiyota, and T. Mukaiyama, Chem.
Lett., 2002, 746.
BnO
BnO
BnO
O
O
O
BnO
BnO
O
BnO
O
BnO
BnO
O
BzO
BzO
BnO
BnO
BnO
SEt
OMe
BzO
13
14
4
5
H. Chiba and T. Mukaiyama, Chem. Lett., 32, 172 (2003).
It was reported that benzyl-protected glycosyl phosphites
were effective donors for ꢀ-stereoselective glycosylations. S.
Hashimoto, K. Umeo, A. Sano, N. Watanabe, M. Nakajima,
and S. Ikegami, Tetrahedron Lett., 36, 2251 (1995).
BnO
BnO
BnO
BnO
BnO
BnO
O
O
O
O
O
O
BnO
BnO
BnO
BnO
BnO
SEt
F
AcO
NPhth
BnO
15
16
Next, in order to extend the scope of the present reaction, ꢀ-
stereoselective glycosylation of various glycosyl acceptors 9
containing a hindered secondary hydroxyl group, thioglycoside
10, 11 and glycosyl fluoride 12 with 3 were tried (Table 2). In all
cases that used glycosyl acceptors having primary hydroxyl
group, the desired disaccharides were obtained in high yields with
high ꢀ-stereoselectivities; however, a moderate ꢀ-stereoselec-
tivity was observed (ꢁ=ꢀ ¼ 27=73) (Entry 1) in the case of
glycosylation using 9. The donor 3, ꢁ-glycosyl 6-nitro-2-
benzothiazoate, gave the ꢀ-saccharide more dominantly com-
pared with ꢁ-glycosyl trichloroacetimidate 6 even when the
hindered acceptor 9 was used (56%, ꢁ=ꢀ ¼ 50=50). Furthermore,
chemoselective glycosylations using ethyl 2,3,4-tri-O-benzoyl-1-
6T. Mukaiyama, H. Jona, and K. Takeuchi, Chem. Lett., 2000,
696.
7
2-Chloro-6-nitrobenzothiazole (2) was prepared by the nitra-
tion (conc. HNO3 and conc. H2SO4) of 2-chlorobenzothiazole
according to the literature method. K. Akasaka, A. Kajiwara,
S. Nagato, Y. Iimura, I. Yoshida, A. Sasaki, M. Mizuno, A.
Kubota, T. Kagaya, and M. Komatsu, W. O. Patent 9308179
(1993).
8
9
Review: R. R. Schmidt and W. Kinzy, Adv. Carbohydr.
Chem. Biochem., 50, 21 (1994).
H. Jona, H. Mandai, W. Chavasiri, K. Takeuchi, and T.
Mukaiyama, Bull. Chem. Soc. Jpn., 75, 291 (2002), and
related references are also herein.