- 學位論文
棘皮類神經節苷脂異類型SJG-1天然物及其具有岩藻醣單元之類似物的全合成研究
Study on the Total Synthesis of Echinodermatous Ganglioside iso-Type SJG-1 and their Analogue with the Fucose Unit
摘要
本論文主要旨在建構出具神經再生活性的異類型SJG-1 (stichopus japonicas ganglioside) 天然物及其與岩藻醣單元之類似物，並探討其生物活性的差異。 以化學選擇性醣苷化反應及[1+1+2]的收斂式合成策略可以快速建構出異類型SJG-1的基本骨架。其中的葡萄糖醣衍生物Glc-6St及唾液酸衍生物Neu-5的醣苷化反應(glycosylation)中，可得到極佳立體選擇性( α : = 17 : 1)及產率尚好70%的混合物雙醣NG-1。而NG-1與LF-1或LF-2的醣苷化反應中，可得到極佳立體選擇性( only)及高產率80%、78%的神經節苷脂NGLF-1、NGLF-2。。 建構α位向岩藻醣中，以C3、C4為Bz保護基的Fuc-6與G2片段的醣苷化反應中，可得到極佳立體選擇性(α : = 12 : 1)及高產率85%的Fuc-7。 在製備植物神經醯胺 (phytoceramide) LF-1、LF-2中，以收斂式合成(convergent synthesis)策略建構異類型長鏈鹼基，先以(D)-來蘇醣((D)-lyxose)為起始物，建構植物鞘胺醇衍生物Lyx-6，以及以1,8-辛二醇(1,8-octanediol)為起始物建構出具有異類型結構碳鏈Diol-4，之後進行烯烴複分解反應(olefin metathesis reaction)，得到異型植物鞘鞍醇iLyx-9，再與飽和脂肪酸進行醯胺化反應(amidation)，得到神經醯胺 (ceramide) LF-1或LF-2，其優點可建立多樣性的長鏈鹼基(long-chain bases)。
關鍵字
全合成並列摘要
The main purpose of this paper is to construct ios-Type SJG-1 natural products with neuroregenerative activity and their analogs with fucose units, and to explore the differences in their biological activities. The basic skeleton of ios-Type SJG-1 can be rapidly constructed by chemoselective glycosidation reaction and the convergent synthesis strategy of [1+1+2]. Among them, in the glycosylation reaction of the glucose sugar derivative Glc-6St and the sialic acid derivative Neu-5, the mixture disaccharide NG-1 with excellent stereoselectivity ( α : = 17 : 1) and a yield of 70% can be obtained. In the glycosylation reaction of NG-1 with LF-1 or LF-2, excellent stereoselectivity ( only) and high yields of 80% and 78% of gangliosides NGLF-1 and NGLF-2 can be obtained. In the construction of α-form fucose, in the glycosylation reaction of Fuc-6 with C3 and C4 as Bz protecting groups and G2, excellent stereoselectivity (α : = 12 : 1) and Fuc-7 with a high yield of 85% can be obtained. In the preparation of phytoceramides LF-1 and LF-2, heterotype long-chain bases were constructed by a convergent synthesis strategy, and (D)-lyxose was used as the starting material to construct the phytosphingosine derivative Lyx-6 , and using 1,8-octanediol as the starting material to construct Diol-4 with a heterostructured carbon chain, and then carry out an olefin metathesis reaction to obtain a heteromorphic phytosphingoid iLyx-9, which is subjected to an amidation reaction with saturated fatty acids to obtain Ceramides LF-1 or LF-2, which have the advantage of creating diverse long-chain bases.