Process Development and Scale-up of Fully Synthetic Tetracycline TP-2758: A Potent Antibacterial Agent with Excellent Oral Bioavailability
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- 作者：Wu-Yan Zhang ; Cuixiang Sun ; Diana Hunt ; Minsheng He ; Yonghong Deng ; Zhijian Zhu ; Chi-Li Chen ; Christopher E. Katz ; John Niu ; Philip C. Hogan ; Xiao-Yi Xiao ; Nicholas Dunwoody ; Magnus Ronn
- 刊名：Organic Process Research & Development
- 出版年：2016
- 出版时间：February 19, 2016
- 年：2016
- 卷：20
- 期：2
- 页码：284-296
- 全文大小：520K
- ISSN：1520-586X
文摘
Process research and development of the fully synthetic broad spectrum tetracycline TP-2758, with a chiral pyrrolidine side chain at the C-8 position, is described. The process utilizes two key intermediates, 7 and 10, in a convergent approach that allows for manufacturing of sufficient quantities of API to supply preclinical and early clinical development. The pyrrolidine moiety was introduced into the left-hand piece (LHP) 10 with high enantioselectivity using Ellman’s sulfinamide chemistry, and the absolute configuration was confirmed by X-ray crystal structure analysis.