TOTAL SYNTHESIS OF NOVEL AZETIDINONES USEFUL AS BETA-LACTAMASE INHIBITORS AND ANTIBACTERIAL AGENTS

摘要

A process is disclosed for the preparation of compounds of formula I: IMAGE I wherein R is hydrogen, lower alkyl, trichloroethyl, benzyl, p-nitrobenzyl, acetoxymethyl, pivaloyloxymethyl, phthalidyl, or a -CH(CH3)OCOOEt group; R1 is -CH2OH, -CHO, -CH2SH, -CH2NH2, -CH2OCOR2, -COOR2, -CH2NHCOR2, -CH2OR3, or -CH2SR4 where R2 is a lower alkyl, aryl or a heterocyclic ring, R3 is a lower alkyl, benzyl, or trityl, and R4 is a five- or six-member heterocyclic ring containing one or more heteroatoms, which comprises reacting a 4-acetoxy azetidinone with a beta -thioketoester to form a mixture, reacting said mixture with thionyl chloride followed by reaction with a phosphine and a base, ozonolyzing and heating to obtain the compounds of formula I.