合成硫酸化N-乙醯乳醣胺及其衍伸物

Synthesis of N-acetyl Lactosamine Sulfates and Analogues

張琇琄(Hsiu-Chuan Chang)

指導教授 ： 姚清發 ； 林俊宏

國立臺灣師範大學/理學院/化學系/碩士(2010年)

摘要

N-乙醯乳醣胺（N-acetyllactosamine, Gal-b-1,4-GlcNAc, LacNAc）和其衍生物 (Gal-1,3-GlcNAc) 通常以雙醣的重覆單元體存在多醣體 (N-glycans) 的末端，這類化合物在生物活性測試中發現可以抑制B淋巴細胞分化成分泌抗體的漿細胞，間接證明了半乳糖凝集素參與B淋巴細胞分化的過程。最近，本實驗室研究發現：硫酸化N-乙醯乳醣胺及其衍生物對半乳糖結合能力有顯著提升，因此，本篇論文將著重在硫酸化N-乙醯乳醣胺衍生物的合成。合成此類化合物將涉及化學合成中保護基的修飾、醣基化反應、選擇性去保護與硫酸化。依據實驗室先前發展的構築體進行醣予體與醣受體的製備，使用預活化（pre-activation）方法於醣基化反應，並利用活化試劑 Ph2SO-Tf2O，最後可以得到高產率硫酸化 N-乙醯乳醣胺或其衍生物。

關鍵字

乙醯乳糖胺 ； 硫酸化 ； 醣基化 ； 預活化

並列摘要

N-Acetyllactosamine (Gal-b-1,4-GlcNAc, LacNAc) and its 1,3-analogue often exist as repeating disaccharides resided at the non-reducing terminus of N-glycans. These carbohydrates are associated with numerous biological activities. For example, they are known to interact with various types of galectins for the immune-activity of B-cells. Recently the incorporation of sulfate groups to the hydroxyl group(s) was observed to greatly enhance the binding interaction with a variety of proteins. This thesis research aims at the synthesis of these sulfated Gal-1,3-GlcNAc, LacNAc and analogues in order for the purpose of systematic investigation. These target disaccharides were synthesized by the reactions steps of protecting group manipulations, glycosylation, selective deprotection and sulfation. We followed the previously established method to prepare the building blocks of Gal donor and GlcNAc-acceptor. The pre-activation method by using diphenyl sulfoxide-Tf2O was found to be suitable for formation of the desired b-1,3-linkage with satisfying high yields.

並列關鍵字

N-acetyllactosamine ； sulfation ； glycosylation. ； pre-activation

參考文獻

1. Hughes, R. C., Galectins as modulators of cell adhesion. Biochimie 2001, 83, 667-676.

2. Hikita, C.; Vijayakumar, S.; Takito, J.; Erdjument-Bromage, H.; Tempst, P.; Al-Awqati, Q., Induction of terminal differentiation in epithelial cells requires polymerization of hensin by galectin 3. J. Cell. Biol. 2000, 151, 1235-1246.

3. Imberty, A.; Lortat-Jacob, H.; Perez, S., Structural view of glycosaminoglycan-protein interactions. Carbohydr. Res. 2007, 342, 430-439.

4. Kjellen, L.; Lindahl, U., Proteoglycans - Structures and Interactions. Annu. Rev. Biochem. 1991, 60, 443-475.

5. Capila, I.; Linhardt, R. J., Heparin - Protein interactions. Angew. Chem. Int. Ed. Engl. 2002, 41, 391-412.