Synthesis of Thione Analogues of Monobactams

Abstract

AbstractOptically active β‐lactams 4 were treated with Lawesson's reagent (2) or Davy's reagent (3) to give the β‐thiolactams 5. Demethylation of 5 by reduction with dissolved metal gave the 1‐unsubstituted 2‐azetidinethiones 6 which were sulfonated and Boc‐deprotected to provide (3S)‐amino‐2‐thiomonobactamic acids 8. The side chain on nitrogen was introduced by using 1‐hydroxybenzotriazole‐activated acids 9. Deprotection of functional groups in the side chain yielded the β‐thiolactam analogues 11a, 11b of SQ 81,377 and aztreonam (1). These compounds were found to be weakly active against a range of Gram‐negative bacteria.