神經再生藥物的開發研究:醣苷神經胺酯質OSG-1 類似物之單元建構體的製備

Abstract

The compound OSG-1, isolated from the sea cucumber Ophiocoma scolopendrina, is a ganglioside containing disaccharides. The synthesis of OSG-1 and its building blocks , such as N-acetylneuramic acid (Neu5Ac), glucose, phytosphingosine and α-hydroxyfatty acid will be discussed in this thesis. The building unit, Neu-3, was synthesized starting from sialic acid via a three-step procedure, involving esterification, per-O-acetylation, and thiophenol glycolsylation in 86% overall yield. The glucose building unit, Glc-6, was prepared using glucose as starting material through a six-step sequence, involving per-O-acetylation, 4-methoxyphenol glycolsylation, deacetylation, protection of primary alcohol, benzylation and deprotection primary alcohol, to give the product Glc-6 in a overall yield of 37%. The building unit of phytosphingosine, Lyx-7, was using lyxose as starting material through a seven-step sequence, involving O-isopropylidene reaction, protection of primary alcohol, Wittig reaction, azidization and functional group transformation to give the product Lyx-7 in a overall yield of 21%. The prepartion of α-hydroxyfatty acid was carved by a facile route in this thesis. The building unit of α-hydroxyfatty acid, Mal-6, is made from D-(+)-malic acid through cyclohexylidene protection reaction, thioethanol glycolsylation, Wittig reaction, hydrogenation and hydrolysis to give the product, Mal-6, in 34%.