標題: alpha-Glycosylation by D-Glucosamine-Derived Donors: Synthesis of Heparosan and Heparin Analogues That Interact with Mycobacterial Heparin-Binding Hemagglutinin
作者: Zulueta, Medel Manuel L.
Lin, Shu-Yi
Lin, Ya-Ting
Huang, Ching-Jui
Wang, Chun-Chih
Ku, Chiao-Chu
Shi, Zhonghao
Chyan, Chia-Lin
Irene, Deli
Lim, Liang-Hin
Tsai, Tsung-I
Hu, Yu-Peng
Arco, Susan D.
Wong, Chi-Huey
Hung, Shang-Cheng
應用化學系
Department of Applied Chemistry
公開日期: 30-May-2012
摘要: Numerous biomolecules possess alpha-D-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted beta-isomer. We report herein a versatile approach in affording full alpha-stereoselectivity built upon a carefully selected set of orthogonal protecting groups on a D-glucosaminyl donor. The excellent stereoselectivity provided by the protecting group combination was found independent of leaving groups and activators. With the trichloroacetimidate as the optimum donor leaving group, core skeletons of glycosylphosphatidyl inositol anchors, heparosan, heparan sulfate, and heparin were efficiently assembled. The orthogonal protecting groups were successfully manipulated to further carry out the total syntheses of heparosan tri- and pentasaccharides and heparin di-, tetra-, hexa-, and octasaccharide analogues. Using the heparin analogues, heparin-binding hemagglutinin, a virulence factor of Mycobacterium tuberculosis, was found to bind at least six sugar units with the interaction notably being entropically driven.
URI: http://hdl.handle.net/11536/16297
ISSN: 0002-7863
期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
Volume: 134
Issue: 21
結束頁: 8988
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