Studies related to the structures of the olivanic acids MM 13902, MM 4550 and MM 17880 : Three β-lactam antibiotics from streptomyces olivaceus

Abstract

MM 13902, a β-lactam antibiotic isolated from Streptomyces olivaceus, has been identified as ( 5R6R)- 3- [( E)- 2- acetamidoethenylthio]- 6- [( S)- 1- hydroxysulphonyloxyethyl]- 7- oxo- 1- azabicyclo [3.2.0] hept- 2- ene- 2- carboxylic acid ( 2) by chemical and spectroscopic studies. The related olivanic acids MM 4550 and MM 17880 have been shown to be the corresponding 3- [( E)- 2- acetamidoethenylsulphinyl]- and 3- (2- acetamidoethylthio)- derivatives ( 1 and 5), respectively. A number of carboxylate and sulphate esters of 1, 2 and 5 have been prepared. A key reaction in the characterisation of 2 was the oxidative degradation of its C-2 monomethyl ester ( 12) in dimethylsulphoxide to methyl 3 -[( E)- 2- acetamidoethenylthio]- 5- [( 1R,2S)- 1- carboxy- 2- hydroxysulphonyloxyprop- 1- yl]pyrrole- 2- carboxylate ( 22). The configuration of the C-6 substituent of 2 was determined by a stereospecific elimination reaction of its ethyl sulphate, p-nitrobenzyl carboxylate ( 19) to yield the 6- ( E)- ethylidene derivative ( 32). MM 13902 was oxidised to MM 4550 with m-chloroperbenzoic acid.