利用苄胺基甲酸酯做為新穎之保護基並建構1,2-β反式醣苷鍵與其應用於多醣合成之研究

Abstract

在合成寡醣分子中，醣基化反應的位向選擇性是非常重要的，鄰基效應一般常用於建立具有高度選擇性的1,2-反式醣苷鍵；然而，常用於鄰基效應的酯基卻很容易在鹼性的條件下被去除，因此在合成複雜的多醣類的時候限制了酯基的應用性。 在本研究當中，我們建立一個新的保護基團：2-O-N-benzylcarbamate應用於建立良好位向選擇性的醣基化反應，我們利用2-O-N-benzylcarbamate來合成雙醣以及常見於酵母菌細胞壁上的組成：β-(1→6)-glucan。由於當醣受體的立體障礙愈加明顯時，帶有2-O-N-benzylcarbamate的醣受體便無法順利與之進行醣基化反應 (通常只有極微量的產物或沒有反應)，為了瞭解這樣的現象，我們使用核磁共振 (NMR)來捕捉64所產生的中間產物，發現了C-1帶有三氟甲磺酸基團的化合物107，這個反應性較差的中間體可能解釋了這個保護基在與立體障礙較大的葡萄醣四號位置的限制性。 N-benzylcarbamoyl 基團可以利用四丁基亞硝酸銨來進行選擇性去保護而不影響其他如：酯基、醚基以及醚硫基等保護基團，且N-benzylcarbamoyl 基團能夠忍受較為極端的條件而不受影響，這樣的特性使得N-benzylcarbamoyl 基團可以做為一個二號位置的保護基來達到良好1,2-反式醣苷鍵的結果。

Stereoselective glycosylation is fundamentally important for the synthesis of oligosaccharide. Neighboring-participating of 2-O-carboxylate ester is responsible for the facile and highly stereoselective synthesis of 1,2-trans class of glycosidic bonds. However, the property of base-labile of ester might limit its application in the synthesis of complex oligosaccharide that requires delicate protective group manipulations. In this study, 2-O-N-benzylcarbamate was introduced as a new protecting group for β–selective glycosylation. Our results exemplified the utility of 2-O-N-benzylcarbamate in the construction of disaccharide and naturally occurring yeast cell wall component: β-(1→6)-glucan. The steric hindrance glycosyl acceptors encountered with the problem of low yield (or no reaction) when they were glycosylated with 2-O-N-benzylcarbamate glycosyl donor. To understand the mechanism of this reaction, nuclear magnetic resonance (NMR) was applied to trap the activated intermediate of compound 64. The less reactivity of 1-OTf-intermediate 107 was detected which might explain the limitation of this protecting group in the glycosylation with the very sterically demanding glucose 4-OH acceptors. N-Benzylcarbamoyl group can be selective removed by tetrabutylammonium nitrite without affecting other groups, such as ester, ether, and thiol ether groups and can be also retained under harsh deprotection processes. These highly selective properties made N-benzylcarbamoyl a unique and useful protecting group for 2-O-position of glycosyl donor for 1,2-trans-glycosylation.