Studies related to penicillins. Part VI. The conversion of penicillin V and 6-aminopenicillanic acid into cepham derivatives

Abstract

Phenoxymethylpenicillinoyldiazomethane (4) reacts with hydrochloric acid to afford a mixture of phenoxymethylpenicillinoylmethyl chloride (5) and (αR)-α-{(2R,5S)-4,4-dimethyl-6-oxo-3-thia-1-azabicyclo[3,2,0]heptan-2-yl}-α-(phenoxyacetamido)acetic acid (15). The chloro-ketone (5) rearranges to 4-isopropylidene-3-oxo-7β-phenoxyacetamidocepham (13) in the presence of 1,5-diazabicyclo[4,3,0]non-5-ene. Under similar conditions 6β-aminopenicillanoylmethyl toluene-p-sulphonate (8) affords 7β-amino-2-isopropylidene-3-oxocepham (14).