簡潔的製備PI-88類寡醣結構化合物以及其醣基化反應

Abstract

此篇論文使用了簡潔方便的方法以合成PI-88類寡醣化合物。PI-88是由一系列甘露六環醣單元所組成， 且PI-88已經被證實具有防止腫瘤增生的功能。PI-88的結構中包含了帶負電荷的硫酸根基團，此帶電荷的基團可以破壞肝素磷酯硫酸基與身體中的腫瘤增生潛在因子之間的作用力，阻止了腫瘤增生的基本步驟發生。許多有關PI-88合成的文獻已經被發表，但這些方法或許都帶有一些缺點。此篇論文使用了許多不同的合成策略，包括了前置預活化醣基化反應、正交醣基化反應以及活性考量醣基化反應。由簡單的甘露六環單醣建構單元開始，我們合成了一系列甘露六環雙醣、三醣、四醣以及五醣的化合物。除此之外，我們也可以在所合成出來的PI-88類寡醣化合物特定位置上精準的修飾硫酸根基團。

This thesis describes a concise synthetic route of PI-88 analogue. PI-88 consists of a series of oligomannan, which have been proved that it could avoid tumor growth. Negatively charged sulfate groups on PI-88 enables it interrupts the interaction between heparin sulfate with fibroblast factors, thus prevent the fundamental step of tumor growth. Many research literature about synthesis of PI-88 analogue has been published, however, they may suffer from some disadvantages. In this thesis, different type of synthetic strategy including pre-activation glycosylation, orthogonal glycosylation, reactivity-based (armed-disarmer) glycosylation have been considered. Starting with three simple monosaccharide building blocks, oligomannan dimer, trimer, tetramer, and prntamer could be well prepared. Besides, demonstration of specifically-installed sulfate groups on PI-88 analogue is also shown in this thesis.