Development of a Second-Generation Process to Antibacterial Candidate Sulopenem
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- 作者：Steven J. Brenek ; St茅phane Caron ; Esmort Chisowa ; Roberto Colon-Cruz ; Mark P. Delude ; Michele T. Drexler ; Robert E. Handfield ; Brian P. Jones ; Durgesh V. Nadkarni ; Jade D. Nelson ; Mark Olivier ; R. Matt Weekly ; G. C. A. Bellinger ; Zinka Brkic ; Neil Choi ; Joe Desneves ; Marcia A.-P. Lee ; Wayne Pearce ; Jessica K. Watson
- 刊名：Organic Process Research & Development
- 出版年：2012
- 出版时间：August 17, 2012
- 年：2012
- 卷：16
- 期：8
- 页码：1338-1347
- 全文大小：503K
- 年卷期：v.16,no.8(August 17, 2012)
- ISSN：1520-586X
文摘
The research, development, and scale-up of the broad-spectrum antibacterial candidate sulopenem are presented. An enabled medicinal chemistry synthesis of this active pharmaceutical ingredient was utilized for Phase 1 and early Phase 2 manufacture but was not conducive to larger scale. The limitations associated with the first-generation synthesis were partially addressed in an improved second-generation synthesis of the target molecule where the penem ring is constructed via a modified Eschenmoser sulfide contraction sequence. Other highlights of the second-generation process include an improved synthesis of an important trithiocarbonate intermediate and a superior process for Pd-catalyzed deallylation of the penultimate ester to obtain low levels of residual palladium.