Process Development and Scale-up of Fully Synthetic Tetracycline TP-2758: A Potent Antibacterial Agent with Excellent Oral Bioavailability

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 o...

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Bibliographic Details
Published in:Organic process research & development 2016-02, Vol.20 (2), p.284-296
Main Authors: Zhang, Wu-Yan, Sun, Cuixiang, Hunt, Diana, He, Minsheng, Deng, Yonghong, Zhu, Zhijian, Chen, Chi-Li, Katz, Christopher E, Niu, John, Hogan, Philip C, Xiao, Xiao-Yi, Dunwoody, Nicholas, Ronn, Magnus
Format: Article
Language:English
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.5b00404