One-pot Glycosylation in the Synthesis of Oligosaccharides

 Carbohydrates and glycoconjugates play key roles in crucial biological processes. Efficient strategies for the synthesis of complex oligosaccharides have been developed in which most of the synthetic effort is directed towards the preparation of saccharide building blocks that can be assembled into complex structures using a minimal number of synthetic steps. In a linear glycosylation strategy, a glycosylation product is converted to either a glycosyl donor by introducing a leaving group at the anomeric position, or a glycosyl acceptor by selective deprotection on the desired hydroxy group. Eliminating these tedious processes should lead to a strategy for the rapid synthesis of oligosaccharides.

One-pot glycosylation is a simple method for sequential glycosyl-bond formation carried out in the same flask. There are two ways.

1. Utilizing the difference in reactivity influenced by glycosyl donors (1)
D. Kahne et al. reported that the glycosylation of monosaccharides 1, 2, and 3 takes place in a sequential manner with 4-methoxyphenyl sulfoxide 2 activating faster than phenyl sulfoxide 1 and C-4 alcohol 3 reacting faster than C-4 silyl ether 2. The desired cyclamycin trisaccharide 5 produced in the one-pot reaction has an anomeric phenyl sulfide, which can be used for the following formation of a glycosyl linkage. This has resulted in a dramatic saving of time and labor (less than 3 h from monosaccharides to purified trisaccharide).
In 1999, C.-H. Wong et al. examined the relative reactivity values of various 4-methylpheyl thioglycosides and developed a computer program for use as a database search tool and guide for the selection of building blocks for the one-pot assembly of a desired oligosaccharide (2).

2. Utilizing the different combinations of activating groups of glycosyl donors and their activating reagents (3)
Takahashi et al. reported that the glycosylation of glycosyl bromide 6 and thiophenyl glycoside 7 initially takes place in the presence of AgOTf that selectively activates 6, following the sequential treatment with 9 and a SPh-activating reagent. This resulted in the formation of linear trisaccharide 11. The glycosylation of 6, 8, and diol 10 provided branched trisaccharide 12 with glycosyl bromide 6 selectively activated by AgOTf and C-6 hydroxy group of 10 rather than by the less active C-3 hydroxy group and via sequential reaction with thiophenyl glycoside 8 and the C-3 hydroxy group of C-6 glycosylated 10. It is noted that the activation of thiophenyl group was achieved in the same flask where the first glycosylation using glycosyl bromide and AgOTf had been carried out.
Further studies of the relative reactivity values of other glycosyl donors will strongly help the synthesis of the oligosaccharide library.
Takashi Takahashi(Department of Applied Chemistry, Graduate School of Science and
Engineering, Tokyo Institute of Technology)
References (1) S, Raghavan, D, Kahne, J. Am. Chem. Soc. 115, 1580-1581, 1993
(2) Z, Zhang, IR, Ollmann, X-S, Ye, R, Wischnat, T, Baasov, C-H, Wong, J. Am. Chem. Soc. 121, 734-753, 1999 and references therein.
(3) H, Yamada, T, Harada, H, Miyazaki, T, Takahashi, Tetrahedron Lett. 35, 3979, 1994; H, Yamada, T, Kato, T, Takahashi, Tetrahedron Lett. 40, 4581, 1999
Mar. 15, 2000

GlycoscienceNow INDEX Return to Top Page