β-Lactamase-stable penicillins. Synthesis and structure–activity relationships of (Z)-alkyloxyimino penicillins; selection of BRL 44154

A series of (Z)-2-alkyloxyimino-2-(2-aminothiazol-4-yl)acetamidopenicillins has been prepared. New methodology has been developed to prepare tertiary alkyl oximes. High stability to β-lactamases and potent antibacterial activity have been achieved against Gram-positive and certain Gram-negative organisms. Activity against methicillin-resistant Staphylococcus aureus was an unexpected finding. The cyclopentyl analogue 4f, BRL 44154, has been selected for further study.