曼诺胺素α和β的总合成
Bo Wang1, Yunpeng Liu1, Rui Jiao1
1Department of Chemistry, The Pennsylvania State University , University Park, Pennsylvania 16802, United States.
Journal of the American Chemical Society
|February 26, 2016
概括
人类首次合成了对抗耐药细菌的强效抗生素曼诺菌素. 这一突破涉及新型黄金催化N-糖化,在这些糖天然产品中构建复杂的糖链.
科学领域:
- 有机化学
- 医学化学
- 自然产品合成
背景情况:
- 曼诺胺是具有显著抗生素作用的糖天然产物,可对抗多种药物耐药的格拉姆阳性细菌.
- 它们的复杂结构具有不寻常的氨基酸,如β-氨酸和复杂的O-和N-结合的糖化模式.
研究的目的:
- 报告mannopeptimycinsα和β的第一个总合成,包括它们的完全精制的N和O结合糖.
- 开发高效的合成策略,在曼诺胺中构建具有挑战性的糖链接.
主要方法:
- 采用黄金催化N-糖化,以高效率和立体选择性合成受硬质阻碍的N-Man-D-βhEnd单元.
- 用于制备L-βMePhe单元的是催化C-H化.
- 循环基架的融合组装,然后进行全球解脱保护.
主要成果:
- 通过完整的N-和O-糖化,成功合成了曼诺胺α和β.
- 准备了包括L-βhEnd,D-Tyr(di-Man) 和L-βMePhe在内的关键构件.
- 黄金催化N-糖化对于有效形成具有挑战性的N-Man-D-βhEnd部分至关重要.
结论:
- 第一次全合成曼诺胺α和β证明了制造这些复杂的糖天然产品的可行性.
- 开发的合成方法,特别是黄金催化N-糖化,为获取相关复杂分子提供了有价值的工具.
- 这项工作为进一步研究曼诺菌素的生物活性和潜在治疗应用铺平了道路.
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