group, cleavage of the acyl-protecting group of the resulting
monoglucoside, and introduction of the second sugar. On
the other hand, the direct introduction of the 2-O-glycosylated
glucosyl donors can change the synthetic route to a conver-
gent one. However, this method has often provided a mixture
of anomeric isomers [Figure 1, (2)]8 because there is no
positive factor enhancing the â-selectivity such as neighbor-
ing group participation. Therefore, the development of a
method for the highly â-selective and direct introduction of
a 2-O-glycosylated glucosyl moiety would facilitate the
synthesis of the 2-O-glycosylated â-O-glucosides.
We recently reported that the restricted twist-boat con-
formation of a glucosyl donor could provide a highly
â-selective glucosidation without the need for traditional
control methods such as through the participation of neigh-
boring groups, solvent effects, or properties of the leaving
groups that produce SN2-like displacements [Figure 2, (3)].9
by 1, and the 2-O-triisopropylsilyl (TIPS) group hinders the
approach of a glucosyl acceptor from the R-face to afford
the corresponding â-O-glucoside. Such ring restrictions have
also resulted from the introduction of bulky trialkylsilyl
groups into the 3-O and 4-O positions.10 In light of these
combined observations, it occurred to us that the silyl group
on the 2-O position could potentially be replaced by sugars
[Figure 2, (4)]. We herein report that disaccharide donors,
that is, ethyl 2-O-(2,3,4-tris-O-tert-butyldimethylsilyl-â-D-
xylopyranosyl)-3,4,6-tris-O-tert-butyldimethylsilyl-1-thio-â-
D-glucopyranoside (2), ethyl 2-O-(2,3,4-tris-O-tert-butyldi-
methylsilyl-R-L-rhamnopyranosyl)-3,4,6-tris-O-tert-butyldi-
methylsilyl-1-thio-â-D-glucopyranoside (3), and ethyl 2-O-
(2,3,4,6-tetrakis-O-tert-butyldimethylsilyl-â-D-glucopyrano-
syl)-3,4,6-tris-O-tert-butyldimethylsilyl-1-thio-â-D-glucopy-
ranoside (4), displayed a preference for highly â-selective
glycosidation. This is a new method for the highly â-selective
and direct formation of 2-O-glycosylated glucosides that is
based upon conferment of a twist boat conformation in the
sugar acceptor undergoing glycosylation.
The disaccharides 2-4 were stereoselectively synthesized
by the respective glycosylation of a thioglucoside 511 with
trichloroacetimidates 6-8, followed by deprotection and
introduction of TBS groups (Scheme 1). Thus, BF3‚Et2O-
catalyzed xylosylation of 5 with 612 in CH2Cl2 afforded
disaccharide 9 â-selectively. The acetyl groups in 9 were
first removed to provide the hexaol 10, to which the TBS
groups were introduced by heating the mixture of 10,
(5) Recently reported glycosides of steroids containing A: (a) Hayes,
P. Y.; Hasylla Jahidin, A.; Lehmann, R.; Penman, K.; Kitching, W.; De
Voss, J. J. Tetrahedron Lett. 2006, 47, 6965-6969. (b) Ono, M.; Nishimura,
K.; Suzuki, K.; Fukushima, T.; Igoshi, K.; Yoshimitsu, H.; Ikeda, T.; Nohara,
T. Chem. Pharm. Bull. 2006, 54, 230-233. (c) Zhou, X.; He, X.; Wang,
G.; Gao, H.; Zhou, G.; Ye, W.; Yao, X. J. Nat. Prod. 2006, 69, 1158-
1163. (d) Fujiwara, Y.; Takaki, A.; Uehara, Y.; Ikeda, T.; Okawa, M.;
Yamaguchi, K.; Ono, M.; Yoshimitsu, H.; Nohara, T. Tetrahedron 2004,
60, 4915-4920.
(6) Kinghorn, A. D.; Kim, N.-C. DiscoVering new natural sweeteners,
Optimising Sweet Taste in Foods; Woodhead and CRC: Cambridge and
Boca Raton, 2006; pp 292-306.
(7) Stepwise constructions of glycosides containing A: (a) Hou, S.; Zou,
C.; Zhou, L.; Lei, P.; Yu, D. Chem. Lett. 2005, 34, 1220-1221. (b) Sun,
J.; Han, X.; Yu, B. Synlett 2005, 437-440. (c) Brito-Arias, M.; Pereda-
Miranda, R.; Heathcock, C. H. J. Org. Chem. 2004, 69, 4567-4570. (d)
Du, Y.; Wei, G.; Linhardt, R. J. J. Org. Chem. 2004, 69, 2206-2209. (e)
Suhr, R.; Pfefferkorn, P.; Weingarten, S.; Thiem. J. Org. Biomol. Chem.
2003, 1, 4373-4379. (f) Nicolaou, K. C.; Michell, H. J.; Jain, N. F.;
Winssinger, N.; Hughes, R.; Bando, T. Angew. Chem., Int. Ed. 1999, 38,
240-244.
(8) Recently reported direct introduction of di- and greater saccharides:
(a) Kim, Y.-J.; Wang, P.; Navarro-Villalobos, M.; Rohde, B. D.; Derryberry,
J.; Gin, D. Y. J. Am. Chem. Soc. 2006, 128, 11906-11915. (b) Hou, S.;
Xu, P.; Zhou, L.; Yu, D.; Lei, P. Bioorg. Med. Chem. Lett. 2006, 16, 2454-
2458. (c) Peng, W.; Li, Y.; Zhu, C.; Han, X.; Yu, B. Carbohydr. Res. 2005,
340, 1682-1688. (d) Zou, C.; Hou, S.; Shi, Y.; Lei, P.; Liang, X. Carbohydr.
Res. 2003, 338, 721-727. (e) Cheng, M. S.; Wang, Q. L.; Tian, Q.; Song,
H. Y.; Liu, Y. X.; Li, Q.; Xu, X.; Miao, H. D.; Yao, X. S.; Yang, Z. J.
Org. Chem. 2003, 68, 3658-3662. (f) Ikeda, T.; Miyashita, H.; Kajimoto,
T.; Nohara, T. Tetrahedron Lett. 2001, 42, 2353-2356. (g) Ikeda, T.;
Kajimoto, T.; Kinjo, J.; Nakayama, K.; Nohara, T. Tetrahedron Lett. 1998,
39, 3513-3516.
Figure 2. Reported â-glucosidation based on the restricted twist-
boat conformation (3), the concept of this paper (4), and disaccha-
ride donors that displayed the â-selective direct glycosidations. PG
) protecting group.
The introduction of bulky trialkylsilyl protecting groups
restricts the conformation of the pyranose ring as illustrated
(4) Recently reported glycosides of terpenoids containing A: (a) Dou,
D.; Li, W.; Guo, N.; Fu, R.; Pei, Y.; Koike, K.; Nikaido, T. Chem. Pharm.
Bull. 2006, 54, 751-753. (b) Cheng, G.; Zhang, Y.; Zhang, X.; Tang, H.;
Cao, W.; Gao, D.; Wang, X. Bioorg. Med. Chem. Lett. 2006, 16, 4575-
4580. (c) Min, B.; Oh, S.; Ahn, K.; Kim. J.; Lee. J.; Kim, D.; Kim, E.;
Lee, H. Planta Med. 2004, 70, 1210-1215. (d) Haddad, M.; Miyamoto,
T.; Lacaille-Dubois, M. HelV. Chim. Acta 2004, 87, 1228-1238. (e)
Suksamrarn, S.; Wongkrajang, K.; Kirtikara, K.; Suksamrarn, A. Planta
Med. 2003, 69, 877-879.
(9) Okada, Y.; Mukae, T.; Okajima, K.; Taira, M.; Fujita, M.; Yamada,
H. Org. Lett. 2007, in press.
(10) (a) Yamada, H.; Tanigakiuchi, K.; Nagao, K.; Okajima, K.; Mukae,
T. Tetrahedron Lett. 2004, 45, 5615-5618. (b) Yamada, H.; Nakatani, M.;
Ikeda, T.; Marumoto, Y. Tetrahedron Lett. 1999, 40, 5573-5576.
(11) Liu, M.-Z.; Fan, H.-N.; Guo, Z.-W.; Hui, Y.-Z. J. Carbohydr. Chem.
1996, 15, 1139-1145.
(12) Mori, M.; Ito, Y.; Ogawa, T. Carbohydr. Res. 1990, 195, 199-
204.
2756
Org. Lett., Vol. 9, No. 15, 2007