Highly α-stereoselective one-pot sequential glycosylation using glucosyl thioformimidate derivatives

Article abstract of DOI:10.1246/cl.2003.172

Several trisaccharides were prepared by efficient highly α-stereoselective one-pot sequential glycosylation using glucosyl p-trifluoromethylbenzylthio-p-trifluoromethylphenyl formimidates (abbreviated to: glucosyl thioformimidates) in the presence of a ca

Full text of DOI:10.1246/cl.2003.172

172
Chemistry Letters Vol.32, No.2 (2003)
Highly ꢀ-Stereoselective One-pot Sequential Glycosylation Using Glucosyl Thioformimidate
Derivatives
Hiroyuki Chiba and Teruaki Mukaiyamaꢀ
The Kitasato Institute, Center for Basic Research, TCI, 6-15-5 Toshima, Kita-ku, Tokyo 114-0003
(Received October 28, 2002; CL-020911)
Table 1. Highly a-stereoselective glycosylation using both ‘armed’ and
‘disarmed’ glycosyl thioformimidates
Several trisaccharides were prepared by efficient highly ꢀ-
stereoselective one-pot sequential glycosylation using glucosyl
p-trifluoromethylbenzylthio-p-trifluoromethylphenyl formimi-
dates (abbreviated to: glucosyl thioformimidates) in the presence
of a catalytic amount of TfOH. Factors that controlled the high ꢀ-
stereoselectivity were determined by characteristic properties of
thioformimidate groups contained both in glucosyl donor and
acceptor.
OH
O
R3O
OBn
O
OBn
O
R3O
R3O
OR2
(1.0 equiv)
BnO
BnO
BnO
BnO
O
BnO
OR1
BnO
R3O
R3O
O
TfOH (10 mol%)
MS 4A (3 g/mmol)
R3O
α-donor
(1.1 equiv)
OR2
tBuOMe, -78 °C, 1 h
Yield / % (α / β)a
R1
R2
R3
Entry
Development of new strategies for oligosaccharide
synthesis1 is of growing importance and many examples of
preparing various saccharides have been reported: namely,
glycosylations based on strategies such as armed-disarmed,2
latent-active,3 one-pot,4 orthogonal,5 solid-phase,6 two-stage
activation7 and so on were carried out. A one-pot sequential
glycosylation method is among the most promising strategies
because of its efficiency in preparing saccharide-building blocks
with alleviated laborious purification processes. Therefore,
chemical methods for one-pot syntheses of oligosaccharides
have currently been shown by many research groups.8
N-p-CF Ph
S-p-CF Bn
N-p-CF Ph
S-p-CF Bn
3
3
112
2
93 (95 / 5)
Bz
Bz
Bz
Bz
Bn
Bn
3
3
N-p-CF Ph
S-p-CF Bn
NH
CCl
3
3
70 (89 / 11)
3
N-p-CF Ph
S-p-CF Bn
NH
CCl
N-p-CF Ph
S-p-CF Bn
NH
CCl
3
98 (89 / 11)
89 (75 / 25)
97 (55 / 45)
99 (25 / 75)
Me
Me
Me
Me
3
4
3
3
3
5
6
3
3
Several one-pot sequential glycosylation reactions for the
synthesis of liner trisaccharide by utilizing armed-disarmed or
orthogonal strategies were reported from our laboratory.9 Further,
total synthesis of branched hepta-ꢁ-saccharide having phyto-
alexin-elicitor activity was then achieved by using a combination
of glucosyl fluorides and thioglycosides.10 All the ꢁ-linkages of
the saccharide were controlled by the assistance of neighboring
effect of 2-O-benzoyl protecting group. On the other hand,
catalytic and highly ꢀ-stereoselective one-pot sequential glyco-
sylation that satisfies requirements for the efficient synthesis of
complex oligosaccharide has not yet been reported. In this
communication, we would like to report on an efficient catalytic
and extremely high ꢀ-stereoselective one-pot sequential glyco-
sylation by using glucosyl thioformimidates.11;12
It was shown in our previous report12 that the catalytic and
highly 1,2-cis or 1,2-trans stereoselective and chemoselective
glycosylation between armed and disarmed glucosyl thioformi-
midates was effectively achieved at ꢁ78 ꢂC in t-BuOMe or EtCN
by using a catalytic amount of TfOH and MS 4A. It is interesting
to note that the glycoside was formed in good yield with
extremely high 1,2-cis stereoselectivity when t-BuOMe was used
as a solvent under kinetic conditions at ꢁ78 ꢂC. Then, stereo-
selective glycosylations were tried under the same condition by
using glucosyl trichloroacetimidate,13 a donor, with several
acceptors (Table 1). In every case, high 1,2-cis stereoselectivity
was achieved when glucosyl thioformimidate was used as a donor
(entries 1vs2, 3vs 4, 5vs6). In addition, it was alsoshown that the
stereoselectivity of glycosylation was dependent on the nature of
an acceptor, that is, its substituents at anomeric position and its
aThe α / β ratios were determined by HPLC analysis.
protecting groups at C-2, 3, 4 positions (entries 1vs 3 vs 5, 2 vs 4
vs 6). A similar tendency was also observed when ꢁ-isomer14 was
used as a donor (Table 2). It was considered that this high 1,2-cis
stereoselectivity using glucosyl thioformimidate as a donor
turned up by the effect of in situ anomerization,15 that is, the
rate of anomerization of glucosyl thioformimidate from ꢀ-isomer
to ꢁ-one seemed to be faster compared with that of conventional
glucosyl trichloroacetimidate. Thus, the reaction seemed to have
proceeded byits ꢁ-isomer which existed inrapid equilibrium with
more stable ꢀ-isomer. Further, highly ꢀ-stereoselective glyco-
sylation was also observed when disarmed glucosyl thioformi-
midate was used as an acceptor, which was probably because the
above bulky leaving group prevented the acceptor to approach the
donor from ꢁ-side.
Next, one-pot sequential glycosylation was tried (Scheme 1).
In the first step, the armed-disarmed chemoselective glycosyla-
tion between 1 and 2 was performed in the presence of 10 mol% of
TfOH and MS 5A in t-BuOMe at ꢁ78 ꢂC. After 1 was completely
consumed, which was monitored by TLC, the second glycosyla-
tion was carried out to yield the trisaccharide 4a16 in high yield by
successive addition of glucosyl acceptor 3a at ꢁ78 ꢂC and a
gradual raise in its temperature up to 0 ꢂC. Formation of ꢁ-linkage
in the second glycosylation was controlled by the assistance of
neighboring effect of 2-O-benzoyl protecting group of the
disaccharide donor. When glucosyl fluoride 3b was used as an
acceptor, the desired trisaccharide 4b was also obtained in good
yield without giving any damage to a reducing end of the
Copyright Ó 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.2 (2003)
173
Table 2. Highly a-stereoselective glycosylation using both ‘armed’ and
‘disarmed’ glycosyl thioformimidates
OBz
O
OH
O
HO
BzO
BnO
BnO
OBn
O
BzO
OH
1
BnO
O
NR
2
BnO
BnO
OMe
R3O
R3O
O
OBn
O
OBn
O
BnO
1
SR
5 (1.0 equiv)
O
NR
2
3a (1.4 equiv)
-30 °C to 0 °C
R3O
OR2
BnO
BnO
BnO
OR1
O
BnO
SR
(1.0 equiv)
BnO
BnO
R3O
R3O
TfOH (10 mol%)
MS 5A (3 g/mmol)
CH2Cl2, -78 °C to -30 °C
O
R1 = p-CF3Ph
R2 = p-CF3Bn
1 (1.3 equiv)
TfOH (10 mol%)
MS 4A (3 g/mmol)
R3O
β-donor
(1.1 equiv)
OR2
tBuOMe, -78 °C, 1 h
Highly α Stereoselective
OBn
O
Yield / % (α / β)a
R1
R2
R3
Entry
BnO
BnO
OBz
O
N-p-CF Ph
N-p-CF Ph
BnO
3
3
O
74 (92 / 8)
Bz
Bz
Bz
Bz
Bn
Bn
1
2
y. 92%
O
S-p-CF Bn
S-p-CF Bn
BzO
3
3
αβ / ββ = 86 / 14
BzO
BnO
BnO
N-p-CF Ph
NH
CCl
3
3
O
65 (88 / 12)
S-p-CF Bn
3
BnO
N-p-CF Ph
OMe
3
95 (90 / 10)
97 (78 / 22)
98 (86 / 14)
99 (60 / 40)
Me
Me
Me
Me
3
4
S-p-CF Bn
3
Scheme 2. Catalyticone-pot trisaccharide (Glca1-4Glcb1-6Glc) synthesis
using both ‘armed’ and ‘disarmed’ glycosyl thioformimidates.
NH
CCl
3
TfOH (0.48 mg, 3.2 mmmol)at ꢁ78 ꢂC. After the reaction mixture
was stirred for 1h, 3a (17.7 mg, 0.038 mmol) was successively
added at ꢁ78 ꢂC and the temperature was gradually raised up to
0 ꢂC. Then, reaction mixture was quenched by adding saturated
aqueous NaHCO3 at 0 ꢂC. The mixture was filtered through the
pad of celite, and aqueous layer was extracted with CH2Cl2. The
combined organic layer was washed with brine, and dried over
Na2SO4. After filtration and evaporation, the resulted residue was
purified by preparative TLC (hexane/EtOAc 3:1) to give the
desired trisaccharide 4a (39.0 mg, 91%, ꢀꢁ=ꢁꢁ = 96:4).
N-p-CF Ph
3
5
6
S-p-CF Bn
3
NH
CCl
3
aThe α / β ratios were determined by HPLC analysis.
OH
O
OH
O
BzO
BnO
BnO
OBn
O
BzO
3
BzO
1
BnO
R
O
NR
2
BnO
BnO
3a R3 = OMe (α)
3b R3 = F (β)
(1.3 equiv)
BnO
1
SR
2 (1.0 equiv)
O
NR
2
SR
The present research is partially supported by Grant-in-Aids
for Scientific Research from Ministry of Education, Culture,
Sports, Science, and Technology.
TfOH (10 mol%)
R1 = p-CF3Ph
R2 = p-CF3Bn
1 (1.1 equiv)
MS 5A (3 g/mmol)
tBuOMe, -78 °C, 1 h
-78 °C to 0 °C
References and Notes
1G.-J. Boons, in ‘‘Carbohydrate Chemistry,’’ ed. by G.-J. Boons, Blackie
Academic & Professional, London (1998), p 175.
OBn
O
Highly α Stereoselective
BnO
BnO
4a R3 = OMe (α)
BnO
O
2
D. R. Mootoo, P. Konradsson, U. Udodong, and B. Fraser-Reid, J. Am.
Chem. Soc., 110, 5583 (1988).
O
BzO
BzO
y. 91% , αβ / ββ = 96 / 4
4b R3 = F (β)
O
3
R. Roy, F. O. Andersson, and M. Letellier, Tetrahedron Lett., 33, 6053
(1992); G. J. Boons and S. Isles, Tetrahedron Lett., 35, 3593 (1994).
S. Raghavan and D. Kahne, J. Am. Chem. Soc., 115, 1580 (1993).
O. Kanie, Y. Ito, and T. Ogawa, J. Am. Chem. Soc., 116, 12073 (1994).
Review: P. H. Seeberger and W.-C. Haase, Chem. Rev., 100, 4349 (2000).
K. C. Nicolaou, T. J. Caulfield, and R. D. Groneberg, Pure Appl. Chem., 63,
555 (1991).
BzO
BnO
O
4
5
6
7
BnO
y. 76%, αβ / ββ = 95 / 5
3
BnO
R
Scheme 1. Catalyticone-pottrisaccharide(Glca1-6Glcb1-6Glc) synthesis
using both ‘armed’ and ‘disarmed’ glycosyl thioformimidates.
8
9
Review: K. M. Koeller and C.-H. Wong, Chem. Rev., 100, 4465 (2000).
Review: T. Mukaiyama and H. Jona, Proc. Jpn. Acad., 78, 73 (2002).
acceptor. In the case of using glucosyl acceptor 517 having
secondary alcohol at C-4 position, one-pot sequential glycosyla-
tion also proceeded by a similar procedure in CH2Cl2 to afford the
trisaccharide in good yield with high ꢀ-stereoselectivity (Scheme
2).
10 T. Mukaiyama, K. Ikegai, T. Hashihayata, K. Kiyota, and H. Jona, Chem.
Lett., 2002, 730.
11 T. Mukaiyama, H. Chiba, and S. Funasaka, Chem. Lett., 2002, 392.
12 H. Chiba, S. Funasaka, K. Kiyota, and T. Mukaiyama, Chem. Lett., 2002,
746.
Thus, simple and efficient highly ꢀ-stereoselective one-pot
sequential glycosylations were achieved by using glucosyl thio-
formimidates in the presence of a catalytic amount of TfOH. The
factors controlling high ꢀ-stereoselectivity were determined by
the characteristic properties of thioformimidate groups contained
both in glucosyl donor and acceptor. Therefore, it is noted that the
glucosyl thioformimidates are useful both as a donor and an
acceptor for the synthesis of ꢀ-linked oligosaccharide.
The typical experimental procedure of one-pot sequential
glycosylation is as follows: to a stirred suspension of MS 5A
(88 mg), 1 (29.1mg, 0.032 mmol) and 2 (25.0 mg, 0.029 mmol) in
t-BuOMe (2.0 mL) was added a toluene solution (ca. 0.1mL) of
13 R. R. Schmidt and W. Kinzy, Adv. Carbohydr. Chem. Biochem., 50, 21
(1994).
14 NMR data of glucosyl thioformimidate (ꢁ-isomer): 1H NMR (270 MHz,
CDCl3) d 6.08 (d, 1H, J ¼ 7:4 Hz, H-1), 13C NMR (67.8 MHz, CDCl3) d
96.9 (C-1), (ꢀ-isomer): 1H NMR (270 MHz, CDCl3) d 6.71 (brs, 1H, H-1),
13C NMR (67.8 MHz, CDCl3) d 93.7 (C-1).
15 R. U. Lemieux, K. B. Hendriks, R. V. Stick, and K. James, J. Am. Chem. Soc.,
97, 4056 (1975).
16 The structures of trisaccharides are determined by 1H and 13C NMR.
Selected NMR data of 4a (major isomer: Glcꢀ1-6Glcꢁ1-6Glc): 1H NMR
(500 MHz, CDCl3) d 4.45 (d, 1H, J ¼ 3:7 Hz, H-1), 4.72 (d, 1H, J ¼ 3:4 Hz,
H-100), 4.76 (d, 1H, J ¼ 7:9 Hz, H-10), 13C NMR (125 MHz, CDCl3) d 97.3
(C-100), 97.9 (C-1), 100.8 (C-10).
17 Glucosyl acceptor 5 was prepared in 91% yield by migration of 4-benzoyl
group of glucosyl acceptor 212 using TBAF (1.1 equiv) in THF at 0 ꢂC.