Diborane reduction of penicillins: preparation of 7-deoxopenicillanic acid

Abstract

The reduction of 6β-acylamidopenicillanates with diborane is shown to proceed by opening of the β-lactam ring to produce the corresponding amino alcohols. The chemistry of the reduction product from benzhydryl 6β-benzyloxycarbonylaminopenicillanate has been explored, in particular its reaction with methanolic potassium hydroxide; no azetidines are formed. Cyclisation of the amino alcohol prepared from methyl penicillanate may be effected either indirectly, via the corresponding bromide, or directly, by use of a modified Mitsunobu reaction, to produce methyl 7-deoxypenicillanate.