Synthesis and anti-fungal activity of simple β-lactams

Abstract

A series of 4-aryloxy- and 4-arylthioazetidin-2-ones A and B were synthesized by reacting 4-acetoxyazetidin-2-one with phenols or thiophenols and subsequent alkylation at the nitrogen with alkylcarboxymethyl groups. Several compounds had anti-fungal activity in vitro against various strains of Microsporum, Trichophyton and a few also against Candida. A multiple regression analysis of the dependence of minimum inhibitory concentration on T. mentagrophytes from log P and Verloop's parameters L, B 1, B 4 and B 5, although not very satisfactory, seems to indicate that steric parameters are the most important in determining the activity. The strong difference in activity between the enantiomers of 4-phenyl-thioazetidin-2-one lends support to the hypothesis of a possible correlation between the 4 S configuration of the β-lactam and anti-fungal activity, which has been proposed for some natural clavams.