Chemical synthesis of β-(1,3)-glucan oligosaccharide and its application

Abstract

β-(1,3)-Glucan has been used as an anti-cancer drug owing to its immunostimulatory effects. However, the mechanism of the biological activity has yet to be elucidated. Moreover, β-(1,3)-glucans used for the mechanistic studies are heterogeneous mixtures extracted from natural sources. Therefore, structure-defined β-(1,3)-glucans are required to simplify the effect caused by β-(1,3)-glucans in the study of the biological activity, and this requirement prompts the study of chemical synthesis of β-(1,3)-glucans. The glycosylation for formation of the β-(1,3)-linkage is difficult because the reactivity of the 3-hydroxy group is suppressed due to considerable steric hindrance from the protecting group at the 4-position in glucose. Moreover, introduction of protecting groups that can be deprotected selectively on the 3-position as well as the 6-position is required to synthesize β-(1,3)-glucans with a branch at the 6-position, and the synthetic method should be optimized by considering the influence of the combined protective groups on the glycosylation. Recently, β-(1,3)-glucan oligosaccharide synthesis using a 4,6-O-benzylidenated glycosyl donor and acceptor has been studied strenuously, and the reactivity of the acceptor and the stereoselectivity of β-(1,3)-glycosylation were substantially improved. Consequently, linear β-(1,3)-glucan of up to 16 saccharides could be synthesized. There have been reports of a few promising examples of multiple introductions of branch residues to the linear backbone of β-(1,3)-glucan. Moreover, some applied studies using synthetic β-(1,3)-glucan oligosaccharides have already been conducted.