便利的醣質反應策略製備含b-苷露醣之寡醣體及芳香族立體選擇醣質反應與其應用性

Abstract

本論文主要分為兩大部份:

1. 本論文第一部份係運用逆加成程序進行一有效力orthogonal □-苷露醣質反應。此一新的醣質化反應合成程序，運用已研發有效力之階段式合成策略，以快速生合成出N-linked glycproteins醣蛋白之核心三醣體Man-□(1,4)-GlcNAc-□(1,4)-GlcNAc與沙門氏菌細胞囊膜之單位三醣體Man-□(1,4)-Rha-□(1,3)-Gal。

2. 第二部份運用一簡便的三氯乙醯氨絡化物乙醯化基醣予體進行實用且有效力的控制□-立體選擇性aromatic醣質反應。此合成方法特別對三氯乙醯氨絡化物L-岩藻醣予體與2-azido-2-deoxy-D-半乳醣予體更有效獲得主要□-立體選擇性產物，此一合成方法的通用性已加以論證: (1)已生合成獲得立體專一性化合物4-methylumbelliferyl □-T-antigen加以論證、(2)有效率的合成出L-岩藻醣基質小分子庫、(3)使用L-岩藻醣基質分子庫研究解釋L-岩藻醣酶的反應機構。

First part of this thesis reports an effective orthogonal □-mannosylation method by adopting an optimized inverse-addition procedure. This new glycosylation procedure enables the development of an efficient sequential strategy for expedited synthesis of trisaccharide core of N-linked glycoproteins, Man-□(1,4)-GlcNAc-□(1,4)-GlcNAc and trisaccharide unit of bacterial capsule in Salmonella bacteria, Man-□(1,4)-Rha-□(1,3)-Gal. The second part describes a practical and efficient □-selective aromatic glycosylation by employing easily available per-O-acetyl glycopyranosyl imidate donors. The method is particularly effective for L-fucopyranosyl and 2-azido-2-deoxy-D-galatosaminyl donors, with which exclusive □-selectivity was achieved. Synthetic utilities of this method was demonstrated in (1) stereoselective synthesis of biological relevant 4-methylumbelliferyl □-T-antigen; (2) efficient synthesis of small libraries of aryl □-L-fucopyranosides; and (3) use of fucopyranoside libraries for elucidation of reaction mechanisms of human L-fucosidase.