Synthesis of Thione Analogues of Monobactams

Optically 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 (3 S )‐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.