Studies related to penicillins and cephalosporins. Part II. An approach to the synthesis of β-lactam antibiotics

Abstract

β-Lactams having a common nitrogen atom with valine methyl ester and carrying a thio-substituent at the 4-position have been prepared by the reaction of alkyl N-(1-methoxycarbonyl-2-methylpropyl)thioformimidates with a keten, or with an acid chloride and triethylamine. cis-3-Azido-4-benzylthio-1-(1-methoxycarbonyl-2-methylpropyl)-azetidin-2-one (21) was obtained by displacement of the chlorine atom in trans-4-benzylthio-3-chloro-1-(1-meth-oxycarbonyl-2-methylpropyl)azetidin-2-one (20) by azide ion. Subsequent reduction with zinc in acetic acid afforded the corresponding cis-3-amino-4-benzylthio-β-lactam (22). These azetidin-2-ones represent a class of new synthetic compounds which may serve as intermediates in the synthesis of β-lactam antibiotics.