Development of a Second-Generation Process to Antibacterial Candidate Sulopenem

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 limitatio...

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Bibliographic Details
Published in:Organic process research & development 2012-08, Vol.16 (8), p.1338-1347
Main Authors: Brenek, Steven J, Caron, Stéphane, Chisowa, Esmort, Colon-Cruz, Roberto, Delude, Mark P, Drexler, Michele T, Handfield, Robert E, Jones, Brian P, Nadkarni, Durgesh V, Nelson, Jade D, Olivier, Mark, Weekly, R. Matt, Bellinger, G. C. A, Brkic, Zinka, Choi, Neil, Desneves, Joe, Lee, Marcia A.-P, Pearce, Wayne, Watson, Jessica K
Format: Article
Language:English
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Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/op300130p