伪-Glycosylation by d-Glucosamine-Derived Donors: Synthesis of Heparosan and Heparin Analogues That Interact with Mycobacterial Heparin-Binding Hemagglutinin

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• 作者：Medel Manuel L. Zulueta ; Shu-Yi Lin ; Ya-Ting Lin ; Ching-Jui Huang ; Chun-Chih Wang ; Chiao-Chu Ku ; Zhonghao Shi ; Chia-Lin Chyan ; Deli Irene ; Liang-Hin Lim ; Tsung-I Tsai ; Yu-Peng Hu ; Susan D. Arco ; Chi-Huey Wong ; Shang-Cheng Hung
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：May 30, 2012
• 年：2012
• 卷：134
• 期：21
• 页码：8988-8995
• 全文大小：457K
• 年卷期：v.134,no.21(May 30, 2012)
• ISSN：1520-5126

文摘

Numerous biomolecules possess 伪-d-glucosamine as structural component. However, chemical glycosylations aimed at this backbone are usually not easily attained without generating the unwanted 尾-isomer. We report herein a versatile approach in affording full 伪-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.