合成以N-乙醯乳醣胺為核心之三醣分子

Synthesis of Galb-1,3/1,4-GlcNAc-based Trisaccharides

徐嘉偉(Chia-Wei Hsu)

指導教授 ： 林俊宏

國立臺灣大學/理學院/化學研究所/碩士(2011年)

https://doi.org/10.6342/NTU.2011.10481

摘要

本篇論文的主題以合成Galb-1,3-GlcNAc (type 1) 、Gal-b1,4-GlcNAc (type 2) 雙醣骨架為基礎，並在這些雙醣的3’、6’、6留下交錯保護基 (orthogonal protecting group) 以便進一步的後修飾，試圖完成三醣分子的合成方法。合成此類化合物將涉及有機醣化學合成中： (1) 醣予體(glycosyl acceptor) /醣受體 (glycosyl donor) 單元的設計與合成；(2) 醣苷鍵 (glycosidic bond) 的建立； (3) 如何選擇不會互相影響的醇類及胺類交錯保護基。
在合成方法的策略上，採取在還原端往後延伸，而在葡萄醣胺的胺上保護基對於醣苷鍵合成做了一系列的討論，而在醣苷鍵生成的位向選擇上則是利用僅調控溶劑系統與鄰近基效應 (neighbouring group participation effect) 來達成。
這些三醣分子構築體的設計可分為三個方向；從半乳醣的三號位置延伸alpha、beta兩種不同的異構物，其中Gal-a-1,3-Gal-b-1,3/1,4-GlcNAc是為人體紅血球上的ABO抗原上四種類型的其中兩種，是第一型與第二型 B antigen；Gal-b-1,3-Gal-b-1,3/1,4-GlcNAc 的b鍵結則是提供合成方法學的探討，最後在更換半乳醣構築體以得到GalNAc-b-1,4-Gal-b-1,4-GlcNAc的三醣分子，則可得到Sda/CT antigen 構築體。

關鍵字

醣化反應 ； 交錯保護基 ； 醣予體 ； 醣受體

並列摘要

This thesis lays an emphasis on the three topics in carbohydrate chemistry including: (1) efficient synthesis of glycosyl acceptors/ glycosyl donors; (2) to construct glycosidic bonds with high yield and stetreoselectivity; (3) to develop orthogonal protecting groups for hydroxyl and amino groups.
We previously prepared a number of Galb-1,3/4-GlcNAc disaccharides with two features. First of all, a functionalized (an azide- or a carboxyester-containing) linker was attached to the reducing terminus of the saccharide products, as well as to be immobilized to the formerly developed carbohydrate array to measure the binding affinity with galectins. Additionally, we utilize orthogonally protecting groups to allow further modifications at specific positions of saccharides such as sulfation of hydroxyl group. In continuation of previous efforts, we aim at synthesizing Galb-1,3/4-GlcNAc-based trisaccharides in this thesis, i.e. the Gal or GalNAc residue will be introduced to the non-reducing end of Gal

並列關鍵字

glycosylation ； orthogonal protecting group ； glycosyl donor ； glycosyl acceptor

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