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

Study on the Development of Neuritogenic Drug: Preparation of the Building Blocks of Ganglioside OSG-1 Analogue

謝清智(Ching-Chin Hsieh)

指導教授 ： 蔡祐輔

中原大學/理學院/化學系/碩士(2007年)

https://doi.org/10.6840/cycu200700837

摘要

OSG-1 化合物是由海洋生物- 蜈蚣櫛蛇尾( Ophiocoma
scolopendrina ) 的肉體體壁部所分離得到，為雙醣之醣苷神經胺基酯
質（ganglioside）化合物。本篇論文旨在研究OSG-1的建構單元體的
合成， OSG-1 的主要成份為唾液酸（ N-acetylneuramic acid,
Neu5Ac）、葡萄糖（glucose, Glc）、植物神經鞘胺醇（phytosphingosine）
與α-羥基脂肪酸（α-hydroxyfatty acid）等四部份。
唾液酸建構單元體Neu-3是由唾液酸為起始物，經酯化反應、多
氧-乙醯化反應及苯硫醣苷化反應得到，總產率為86%。葡萄糖建構
單元體Glc-6是由葡萄糖作為起始物，經多氧-乙醯化反應、甲氧苯酚
基醣苷化反應、去乙醯基反應、一級醇保護反應、苷基化反應、一級
醇去保護基反應等六個反應步驟得到，總產率為37%。植物神經鞘胺
醇建構單元體Lxy-7是由來蘇糖( lyxlose)作為起始物，經氧-異亞丙基
化反應、一級醇保護反應、Wittig反應、疊氮等官能基轉換反應六個
反應步驟得到，總產率為21%。α-羥基脂肪酸的製備，為本研究自行
開拓的一條簡易且快速的合成途徑，α-羥基脂肪酸由D-(+)-蘋果酸
(D-(+)-malic acid)為起始物，經環亞己基保護反應、乙烷硫醣ㄓ柦r
應、Wittig 反應、氫化反應及水解反應等五個反應步驟得到，總產率
為34%。

關鍵字

α-羥基脂肪酸 ； 醣?神經胺基酯 ； 植物神經鞘胺醇

並列摘要

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%.

並列關鍵字

phytosphingosine ； OSG-1 ； ganglioside ； α-hydroxyfatty acid ； sea cucumber

參考文獻

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