Development and Industrialization of New Intermediate GCLE for Cephalosporin Antibiotic Synthesis (Japanese)

Taniguchi, M.*; Misawa, T.*; Shiroi, T.*; Torii, S.; Tanaka, H. (*Otsuka Chemical Co. LTD.), J. Chem. Soc. Jpn., Chemistry and Industrial Chemistry1995, 577.

Synthesis as well as characteristic features of 3-chloromethylcephems (GCLE), a new potent intermediate for the synthesis of wide variety of antibiotics of cephalosporin family, are described. The synthetic scheme of GCLE starting from penicillin G consists of pyrolytic cleavage of penicillin sulfoxide leading to 4-(phenylsulfonylthio)azetidin-2-one derivatives, electrochemical ene-type chlorination of the C(1)-substituent of the azetisinones, and subsequent construction of the cephem framework by ammonia-promoted recyclization. The phenylsulfonyl moiety works effectively for trapping the in situ generated sulfenic acid in the first step, as a protecting group in the ene-type chlorination, and as a good leaving group in the final recyclization step.