具神經再生活性之醣苷神經胺基脂質SJG-1全合成的研究：經由一鍋化─兩步醣苷化反應建立醣脂質骨架

Studies on the Total Synthesis of Ganglioside SJG-1 with Neuritogenic Activity: Via One Pot-Two Steps Glycosylation to Build the Skeleton of Glycolipid

連掌鋒(Jang-Feng Lian)

指導教授 ： 蔡祐輔

中原大學/理學院/化學系/碩士(2008年)

https://doi.org/10.6840/cycu200900197

摘要

天然物SJG-1及與其結構相當的神經鞘胺醣脂質天然物都具有神經再生的生物活性，而文獻上只有一篇相關的醣脂質GM5之全合成被報導，但其合成步驟較為冗長（包含建構單元體共三十步）。基於生物功能及簡化合成步驟的原因，引發本實驗室對此類化合物之全合成研究的興趣。
本論文著重以一鍋化－兩步（或多步）反應的方法研究，以能有效製備所需建構單元體和SJG-1及與其結構相當的神經鞘胺醣脂質化合物。
本論文有關氯化唾液酸衍生物Neu-4的製備，其操作及再現性皆比AcCl/MeOH（acetyl chloride / methanol）的條件較佳且有不錯的產率（83%）。葡萄醣建構單元體Glc-2是以葡萄醣為起始物，經由一鍋化－三苯甲基取代反應與苯甲醯酯化反應及一鍋化－去三苯甲基反應與取代反應等兩次一鍋化－兩步反應製得，總產率為60%。迄今，此種合成策略在文獻上並未被報導。有關其它建構單元體，我們依循文獻上的方法製備得到。
經由一鍋化－兩步醣苷化反應，我們可以製得具有唾液酸、葡萄醣與十六烷等成分的醣脂質化合物67與67，總產率為43%。

關鍵字

醣 ； 醣?神經胺基脂質 ； 神經再生 ； 一鍋化 ； 合成

並列摘要

The natural product SJG-1 and its structurally similar glycosphingolipids have the nerve-growth activity. Only one total synthesis of glycolipid GM5 has been reported so far, but it required 30 overall steps including the preparation of building blocks. Owing to the biological activity, and shortening the synthetic steps, prompted us to study the total synthesis of these compounds.
This thesis focus on one pot-two(or multiple) steps reaction to prepare efficiently the building block of SJG-1, SJG-1, and its equivalent compounds.
The preparation of chloro N-acetylneuraminic acid derivative Neu-4 in our studies is easier and higher reproducibility than the acetyl chloride / methanol （AcCl / MeOH） condition and the yield is moderate（83%）. The building block of Glc-2 is prepared from glucose as starting material via one pot-tritylation and benzoic esterification, and one pot-detritylation and substitution in the 60% overall yield. Up to now, this strategy has not been reported in the literature. For the preparation of the other desired building blocks, we followed the reported strategies.
Via one pot-two steps of glycosylation, we can get glycolipid compound 67α、67β(43% overall yield) which is composed of N-acetylneuramic acid, glucose, and hexadecane.

並列關鍵字

One-Pot ； Ganglioside ； Carbohydrate ； Neuritogenic Activity ； Synthesis

參考文獻

9. Kempermann, G.; Gage, F. H. Scientific American 1999, May 280, 48.

12. Ledeen, R. W. J. Neurosci. Res. 1984, 12, 147.

15. Braune, S. Drugs & Aging 1991, 1, 57.

19. Takahashi, T., Tsukamoto, H., Yamada, H. Tetrahedron Lett. 1997, 38, 8223.

20. Gin, D. Y., Haberman, J. M., Org. Lett. 2001, 3, 1665.