Gb3 與 isoGb3 衍生物之合成及製備 AB3C 型多功能醣規則樹枝狀分子

Abstract

本論文分為兩大部分：

1. Gb3 和isoGb3 三醣分子在生物學上為很重要的寡醣(oligosaccharides)。本論文以二號位置不具鄰助基效應(neighboring group participation effect) 的乳醣給體(D-lactosyl donor) 先與 6-chlorohexanol 受體進行利用溶劑效應(solvent effect)進行低濃度 β- 選擇性醣化反應(low concentration 1,2-trans β-selective glycosylation)，獲得附有 β-linked spacer 的乳醣衍生物(β-lactoside)。由於 β-linked spacer 的乳醣衍生物(β-lactoside)已擁有一個羥基(hydroxyl function)，因此可作為乳醣受體(lactosyl acceptor)與具 DTBS 官能基的半乳醣給體(D-galactosyl donor)進行 α-選擇性的醣化反應(glycosylation)，接着再經過一般常見的去保護反應即可得到 Gb3 和isoGb3 的三醣衍生物。

2. 醣規則樹枝狀分子(glycodendrimers)在研究碳水化合物與蛋白 質間的作用(carbohydrate-protein interaction)上被科學家廣泛的應用。論文研究主題為以非保護的甘露醣質共軛物(D-mannoside conjugates)作為末端部位、以半乳醣衍生物(D-galactoside derivative)作為分支點(branching side)利用點擊化學(Click chemistry)來製備AB3C 型多重功能(multi-functional) 的醣規則樹枝狀分子(glycodendrimers)，並期許能夠有高效率、高產率、簡易分析的優點。

This thesis is divided into two parts:

1. The first part describes the development of a highly efficient preparation of Gb3 and isoGb3 trisaccharide derivatives, both trisaccharides have found important biological functions that attract the attention of scientists. In our schemes, the target trisaccharides are directly produced by three basic components, i.e. linker, lactosyl and galactosyl building blocks. Bifunctional D-thiolactosides without C-2 participating group are employed to make β-linked O-lactosyl building blocks through the low concentration 1,2-trans β-glycosylation of 6-chlorohexanol. As the prepared β-linked O-lactosyl building blocks contain hydroxyl function so that they can be used as D-lactosyl acceptors, which are coupled with the α-directing di-(tert-butyl) silylidene (DTBS) protected thiogalactoside to furnish protected Gb3 and isoGb3 trisaccharide derivatives. After routine deprotection, desired Gb3 and isoGb3 derivatives are obtained in excellent stereoselectivity.

2. Different types of glycodendrimers are employed as synthetic models to mimic natural glycoconjugates in the studies of carbohydrate-protein interactions. The second part of this thesis employed unprotected D-mannosyl conjugate, novel branching unit deriving from galactose and the well-known “Click ligation” to prepare the AB3C type multi-functional glycodendrimers.