治療神經系統疾病之藥物的開發研究： 具不同碳鏈長度脂肪酸多樣性二十碳異植物鞘氨醇-神經醯胺之神經節苷脂Hp-s1類似物的合成

Study on the Development of the Drugs Used in Treating the Neurological Disorders: The Synthesis of the Neuritogenic Ganglioside Hp-s1’s Analogues with Various Eicosaacarbon Isophytosphingosine-Phytoceramide Moiety Containing Different Length of Carbon Chain Fatty Acids

林育如(Yu-Ju Lin)

指導教授 ： 蔡祐輔

中原大學/理學院/化學研究所/碩士(2019年)

https://doi.org/10.6840/cycu201900812

摘要

本論文旨在從事具神經再生之醣脂質天然物Hp-s1類似物的全合成，以尋得治療神經退化性疾病的藥物。
在合成方面，本論文遵循實驗室開拓及文獻的方法，主要利用化學選擇性醣苷化反應，及［1+1+2］收斂式（convergent strategies）的合成策略，已完成兩個具保護基之神經節苷酯Hp-s1之類似物NGLS-2及NGLB-2。
在神經節苷酯Hp-s1之類似物方面，我們首次引進異植物鞘鞍醇。以1,12-十二烷二醇 (1,12-Dodecanediol) 為起始物建構出具異型結構之碳鏈IP12-8，以及以(D)-來蘇糖((D)-Lyxose)建構植物鞘胺醇衍生物Lyx-6，進行烯烴複分解反應得異植物鞘鞍醇iLyx-9。再與飽和脂肪酸進行醯胺化反應，得到神經醯胺 (ceramide) LS-1 及 LB-1。

關鍵字

神經節苷脂Hp-s1類似物 ； 異植物鞘氨醇

並列摘要

This thesis aims to fully synthesize Hp-s1 analogues of neurolipid glycoproteins in order to find drugs for the treatment of neurodegenerative diseases.
In terms of synthesis, this paper follows the laboratory development and literature methods, mainly using chemical selective glycosylation reaction, and [1 + 1 + 2] convergent strategies synthesis strategy, has completed two analogs with protective groups of gangliosides Hp-S1, NGLS-2 and NGLB-2.
For the first time in the analogs of ganglioside Hp-s1, we introduced the isophytosphingosine. Constructing a carbon chain IP12-8 with a heterostructure from 1,12-dodecanediol and constructing a plant with (D)-Lyxose. The sphingosine derivative Lyx-6 is subjected to an olefin metathesis reaction to obtain a phytosphingosine iLyx-9 and then subjected to a guanidine reaction with a saturated fatty acid to obtain ceramide LS-1 and LB-1.

並列關鍵字

Ganglioside Hp-s1’s Analogues ； Isophtosphingosine

參考文獻

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