Direct incorporation of a 6α(7α)-formamido group into penicillin and cephalosporin sulphides and sulphoxides

Abstract

6β(7β)-[N-(2,2,2-Trichloroethoxycarbonyl)-N-trifluoromethylsulphonyl)amino]-penicillins and-cephalosporins have been converted into the corresponding 6α(7α)-formamido-6β(7β)-(2,2,2-trichloroethoxycarbonylamino) derivatives by treatment with N,N-bis(trimethylsilyl)formamide and triethylamine. The trifluoromethyl group could be replaced (in approximately decreasing order of effectiveness) by nonafluorobutyl, pentafluorophenyl, 2,4,5-trichlorophenyl, 2,4-dinitrophenyl, 4-nitrophenyl, p-tolyl, and methyl. The 6α(7α)-formamido-(2,2,2-trichloroethoxy)carbonylamino derivatives were oxidised and the structure of the derived α- and β-sulphoxides confirmed by unambiguous synthesis. The antibacterial activity of the α- and β-sulphoxide isomers of the penicillin (45) is presented.