藉由醣構築體反應性的不同來合成N-乙醯乳糖胺的四醣分子

Synthesis of LacNAc Tetrasaccharide via a Reactivity-based Approach

蕭瑞甫(Jui-Fu Hsiao)

指導教授 ： 林俊宏

國立臺灣大學/理學院/化學研究所/碩士(2012年)

https://doi.org/10.6342/NTU.2012.10804

摘要

醣類在生物體當中扮演著重要的角色，包含細胞與細胞之間的作用、抗體的辨識以及癌症細胞的轉移等等。利用酵素的方法來合成最大的問題是基質與酵素間高度專一性的結合，導致基質不利於再引入其他的修飾。而利用化學合成的方式，其醣體結構上的選擇就相對比較彈性，而且也有利於大量的製備。
本實驗室之前已經發展出有效率的合成出含有交錯保護基(orthogonal protecting group)的Gal-β1,3/4-GlcNAc雙醣分子。而為了要能更進一步的得到更長醣鏈的N-乙醯乳糖胺，希望能利用模組化 (modular synthesis) 的合成方式來達成，而適當的雙醣體便是首要的考慮目標。
本篇論文的主題是希望利用一鍋化合成的策略來合成N-乙醯乳糖胺的四醣分子。實驗分成三個部分：醣予體以及醣受體的選擇，與最後一鍋化合成而得到的目標產物。醣予體的選擇根據翁啟惠教授提出的相對反應活性(relative reactivity value, RRV)的步驟來調查。合成而得的不同反應性的醣予體，依照其反應性的高低差異，最後能利用一鍋化的方式來得到N-乙醯乳糖胺的目標分子。

關鍵字

交錯型保護基 ； 相對反應性 ； 一鍋化合成 ； N-乙醯乳醣胺 ； 模組化合成

並列摘要

Carbohydrates play an important role in numerous biological activities, including cell-cell interactions, recognition of antibodies, and cancer metastasis. Chemical synthesis provides the flexibility and, in addition, allows the preparation to be operated at large scale.
We previously developed an efficient method to prepare Gal-β1,3/4-GlcNAc disaccharides installed with orthogonal protecting groups. In order to prepare Gal-β1,3/4-GlcNAc-containing saccharides of longer chains with high total yields, we propose to utilize a disaccharide donor as a module for fast assembly. The primary concern is to study the reactivity of suitable glycosyl donors. Following the procedure developed by Prof. Wong and coworkers allowed us to obtain the relative reactivity values (RRVs) of various Gal and GlcNAc donors. The result led us to accomplish the one-pot synthesis of a LacNAc-containing tetrasaccharide. Furthermore, we would like to examine the Gal-β1,4-GlcNAc disaccharides’ RRVs. The study not only helps us to understand how incorporation of an addition sugar modulates the donor reactivity, but also makes it possible to synthesize long chain glycans with modular assembly.

並列關鍵字

orthogonal protecting group ； RRV ； one-pot synthesis ； N-Acetyl lactosamine (LacNAc) ； modular synthesis

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