Studies related to penicillins. Part 27. A strategy for the conversion of 1,1-dioxides of penicillanates into 1,1-dioxides of 3-methylceph-3-em-4-carboxylates

Abstract

Methodology for the conversion of benzyl (3S,5R)-penicillanate 1,1-dioxide (2b) into (6R)-4-benzyloxycarbonyl-3-methylceph-3-em 1,1-dioxide (3b) has been devised. In the process, the 3,4-double bond of the product was constructed by a reductive carbonyl-carbonyl coupling reaction, induced by trimethyl phosphite, of benzyl 2-[(2R)-2-acetonylsulphonyl-4-oxoazetidin-1-yl]glyoxylate (12a). This compound was prepared from (2R)-1-(1-benzyloxycarbonyl-2-methylprop-1-enyl)-4-oxoazetidine-2-sulphinic acid (13a), obtained from the precursor (2b) by a β-elimination reaction, by an acetonylation-ozonolysis sequence.

By a similar route, benzyl (3S,5R,6S)-6-chloropenicillanate 1,1-dioxide (2c) was transformed into (6R,7S)-4-benzyloxycarbonyl-7-chloro-3-methylceph-3-em 1,1-dioxide (3d).

The reductive carbonyl–carbonyl coupling reaction was inapplicable to benzyl 2-[(2R,3S)-2-acetonylsulphonyl-4-oxo-3-phenoxyacetamidoazetidin-1-yl]glyoxylate (12c)[prepared from benzyl (3S,5R,6R)-6-phenoxyacetamidopenicillanate 1,1-dioxide (17b)]. However, it could be used to prepare (6R,7R)-4-diphenylmethoxycarbonyl-3-methyl-7-phenoxyacetamidoceph-3-em 1,1-dioxide (8b) from diphenylmethyl 2-[(2R,3R)-2-acetonylsulphonyl-4-oxo-3-phenoxyacetamidoazetidin-1-yl]glyoxylate (19)[obtained by ozonolysis of the cephem dioxide (8b)].