SYNTHESIS OF THIONE ANALOGS OF MONOBACTAMS

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