LETTER
Solid-Phase Synthesis of a Phytoalexin Elicitor-Active Tetraglucosyl Glucitol
913
We have demonstrated that the solid-phase synthesis of
pentasaccharide 1 can be achieved on ArgoPore resin
linked through with a benzoate linker. Although the reac-
tivity of the glycosylation at the 1,3-linkage is not as high
as one having 1,6-linkage, the block-type synthesis using
ethyl 3-O-TBS-thioglucosides A3 and B2 on solid-phase
should provide a potentially useful method for the library
synthesis of phytoalexin elicitors for rice, consisting of -
D-Glc-(1 6) branched, -D-Glc-(1 3) linked deriva-
tives.
BnO
BnO
O
W
P
O
O
BnO
6
OMBz
BnO
Table 1
O
O
BnO
O
9a
OBn
XO
3
3
OY
OY
W = COC6H4O(CH2)3CONH
14 X = Fmoc, P = ArgoPore
15 X = TBS, P = ArgoPore
16 X = H, P = ArgoPore
a
repeated twice
b, A3
BnO
P
O
OMBz
W
BnO
BnO
BnO
O
O
Acknowledgement
O
O
BnO
O
O
BnO
BnO
XO
OBn
O
This study was supported by Special Coordination Funds for Pro-
moting Science and Technology from the Ministry of Education,
Culture, Sports, Science and Technology, Japan to whom we are de-
eply indebted.
OBz
OBz
OBz
17 X = TBS, P = ArgoPore
18 X = H, P = ArgoPore
a
b, A3 repeated twice
References
BnO
R
O
BnO
BnO
BnO
(1) Yamaguchi, T.; Yamada, A.; Hong, N.; Ogawa, T.; Ishii, T.;
Shibuya, N. The Plant Cell 2000, 12, 817.
O
O
OZ
BnO
BnO
(2) Taylor, C. M. In Combinatorial Chemistry; Wilson, S. R.;
Czarnik, A. W., Eds.; John Wiley and Sons, Inc.: New York,
1997, 207.
O
O
BnO
O
O
BnO
O
BnO
OBn
O
O
XO
OY
OY
OY
OY
(3) (a) Yamada, H.; Harada, T.; Takahashi, T. J. Am. Chem. Soc.
1994, 116, 7919. (b) Nicolaou, K. C.; Winssinger, N.;
Pastor, J.; DeRoose, F. J. Am. Chem. Soc. 1997, 119, 449.
(c) Nicolaou, K. C.; Watanabe, N.; Li, J.; Pastor, J.;
Winssinger, N. Angew. Chem. Int. Ed. 1998, 37, 1559.
(d) Geurtsen, R.; Côté, F.; Hahn, M. G.; Boons, G.-J. J. Org.
Chem. 1999, 64, 7828. (e) Plante, O. J.; Palmacci, E. R.;
Seeberger, P. H. Science (Washington D.C.) 2001, 291,
1523. (f) Yamada, H.; Takimoto, H.; Ikeda, T.; Tsukamoto,
H.; Harada, T.; Takahashi, T. Synlett 2001, 1751.
(4) (a) Du, Y.; Zhang, M.; Kong, F. Org. Lett. 2000, 2, 3797.
(b) Yang, G.; Kong, F. Synlett 2000, 1423.
19 X = TBS, Y = Bz, Z = MBz, R = W-ArgoPore
20 X = H, Y = Bz, Z = MBz, R = W-ArgoPore
21 X = Y = Z = R = H (10% overall yield from 9a)
a
c
d, e
1
Scheme 5 a) HF pyridine, THF (95%); b) NIS/TfOH, MS4A,
CH2Cl2; c) 4 N aq NaOH, dioxane–MeOH; d) Pd(OH)2, H2, MeOH–
H2O; e) NaBH4, MeOH–H2O (80%, 2 steps).
(5) Amaya, T.; Tanaka, H.; Yamaguchi, T.; Shibuya, N.;
Takahashi, T. Tetrahedron Lett. 2001, 42, 9191.
group exhibited an armed effect as a glycosyl donor to
provide trisaccharide 15 in 80% conversion.11,19
(6) In Solid Support Oligosaccharide Synthesis and
Combinatorial Carbohydrate Libraries; Seeberger, P. H.,
Ed.; John Wiley and Sons, Inc.: New York, 2001.
(7) Recent reports utilizing an ester linker in solid-phase
glycosylation: (a) Zhu, T.; Boons, G.-J. Angew. Chem. Int.
Ed. 1998, 37, 1898. (b) Egusa, K.; Fukase, K.; Nakai, Y.;
Kusumoto, S. Synlett 2000, 27. (c) Roussel, F.; Knerr, L.;
Grathwohl, M.; Schmidt, R. R. Org. Lett. 2000, 2, 3043.
(8) Deng, S.; Yu, B.; Hui, Y.; Yu, H.; Han, X. Carbohydr. Res.
1999, 317, 53.
The solid-phase synthesis of pentasaccharide 1 was car-
ried out as follows (Scheme 5). Removal of the TBS
group of the polymer-supported trisaccharide 15 with
HF pyridine afforded glycosyl acceptor 16 (>95%). Re-
peated glycosylation of polymer-supported 16 with the
glycosyl donor A3 in the presence of NIS–TfOH provided
tetrasaccharide 17, from which the silyl group was re-
moved by HF pyridine to afford 18. The monosaccharide
A3 was loaded onto 18 by glycosylation utilizing the NIS–
TfOH method, twice, furnishing pentasaccharide 19. Re-
moval of the silyl group of 19 with HF pyridine provided
20. Finally, cleavage from the resin and consecutive de-
benzoylation was performed (4 N aq NaOH, dioxane–
MeOH) to provide the pentasaccharide 21 in 10% overall
yield after silica gel column chromatography and gel per-
meation chromatography (7 steps from 9a, average 72%).
(9) Ek, M.; Garegg, P. J.; Hultberg, H.; Oscarson, S. J.
Carbohydr. Chem. 1983, 2, 305.
(10) Preparation of 2-O-benzoyl derivative instead of 2-O-(4-
methyl)benzoyl one was reported. See: (a) Garegg, P. J.;
Hällgren, C. J. Carbohydr. Chem. 1992, 11, 425.
(b) Ekelöf, K.; Oscarson, S. J. Org. Chem. 1996, 61, 7711.
(11) (a) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-
Reid, B. J. Am. Chem. Soc. 1988, 110, 5583. (b) Fraser-
Reid, B.; Udodong, U.; Wu, Z.; Ottosson, H.; Merritt, J. R.;
Rao, C. S.; Roberts, C.; Madsen, R. Synlett 1992, 927.
(12) Compound 7 was prepared from 2 by deprotection of TBS
(see ref. 3b) and glycosidation of the corresponding 3,6-
hydroxy free phenyl thioglucoside with excess benzyl
alcohol (NIS-TfOH, CH2Cl2, MS 4 Å, 0 °C, 52%).
(13) Commercially available from Argonaut Technologies, San
1
The H and 13C NMR and TOF-mass spectra data are in
accordance with the structure of 21.21 Deprotection of 21
in the presence of Pd(OH)2 under a hydrogen atmosphere,
followed by reduction with NaBH4 afforded the desired 1
in 80% yield, whose spectral data are identical with those
of the synthetic one previously reported.5
Synlett 2002, No. 6, 911–914 ISSN 0936-5214 © Thieme Stuttgart · New York