Die Umwandlung von Penicillinen in Cephalosporine. Modifikationen von Antibiotika, 3. Mitteilung

A new method for the degradation of the thiazolidine ring in penicillins is described. Penicillin V ( 8a ), penicillin G ( 8b ) and 6-t-butoxycarbonylaminopenicillanic acid ( 33 ) (BOC-6-APA) were converted via their acylazides and isocyanates ( 10 and 34 ) into 2,2,2-trichloroethyl urethanes ( 11 and 35 ). Reductive removal of the trichloroethoxycarbonyl groups in an aqueous medium gave the 3-hydroxy-penam-derivatives 13 and 36 . The structure and various reactions of these carbinolamides are discussed in detail. An oxidative radical fragmentation (using lead tetraacylates and light) followed by thermal treatment transformed the 3-hydroxy-penam-derivatives into the N-formyl-β-lactam-thio-enolethers 27 and 37 in which the formyl group could be replaced by hydrogen. Reactions of the β-lactam and thio-enolether functions are described. The BOC-derivative 37 can be transformed into the isomeric compound 3 , an intermediate in Woodward's total synthesis of cephalosporins.