Development of a Practical and Convergent Process for the Preparation of Sulopenem

Abstract

Previous synthetic processes for the preparation of sulopenem involved multistep linear sequences in which the chiral sulfoxide side chain was introduced early in the process. This contribution summarizes the development of a practical and convergent process for the large-scale preparation of 1. The key step in the synthesis involves cyclization of an oxalimide intermediate to provide the thiopenem core. This convergent strategy allows for late introduction of the expensive and labile chiral sulfoxide subunit. Additionally, a regioselective sulfur oxidation and an improved deprotection sequence were developed. The latter provides API of high purity without the need for recrystallization.

Exploiting hexafluoroisopropanol (HFIP) in Lewis and Brønsted acid-catalyzed reactions

“…The development of processes for industrial scale recovery of HFIP by co-distillation with heptanes represents a promising solution for its more extensive use. 61 Finally, none of the examples presented here are enantioselective, despite some stereospecific examples. This is understandable, given the strong H-bond donating ability of HFIP, which prevents the formation of tight ion-pairs with chiral catalysts.…”

T405, a New Penem, Exhibits In Vivo Efficacy against M. abscessus and Synergy with β-Lactams Imipenem and Cefditoren

“…In addition to allowing for the removal of a lengthy and costly silica-gel flash chromatography step, the silyl ether 4 allowed the molecule to be triturated in higher purity. A similar strategy was developed in the industrial synthesis of sulopenem ( 34 ). With compound 4 in hand, the silyl ether is removed to yield compound 5, the common intermediate of the previously described synthesis.…”

Hexafluoroisopropanol as a highly versatile solvent

“…Moreover, industrial procedures for HFIP recovery on large scale have been developed involving co-distillation with heptanes and separation of the immiscible distillate. 3 b) Enhanced Acidity The negative inductive effect as a consequence of fluorination results in a significantly enhanced acidity for HFIP in aqueous solution (pK a = 9.3)…”