SIMPLE AND CONDENSED BETA-LACTAMS .19. SYNTHESIS OF SOME NEW 7-ACYLAMINO-2-ISO-OXACEPHEM-4-CARBOXYLIC ACIDS

General methods have been developed for the synthesis of 7-amino-2-iso -oxacephem-4-carboxylic acid esters 21a,b; 35b. Clayfen [Fe(III) nitra te supported by montmorillonite] was used for the preparation of benzy l 2,3-dioxobutyrate (3). The latter readily reacted with N(1)-unsubsti tuted beta-lactams (9a, 28) to give products formed by addition reacti on on the middle carbonyl-C atom. These intermediates furnished the co rresponding acetoacetic esters 10, 29 which gave by ring closure the O -mono- and the O,N-diprotected-2-iso-oxacephems (11, 30). Intermolecul ar carbene insertion was used for the synthesis of tert-butyl 2-(2-oxo azetidin-1-yl)acetoacetates 19a,b whose ring closure led to the tert-b utyl 2-iso-oxacephem-4-carboxylates 20a,b. The O-protecting tert-butyl group could be removed without decomposition of the 2-iso-oxacephem m oiety to give 2-iso-oxacephem-4-carboxylic acids 2a,b which exhibit an tibacterial activity against Gram-positive microorganisms.