Structure-activity relationships of synthetic antibiotic analogs of anisomycin

Abstract

A general synthetic sequence was used to synthesize a series of anisomycin analogs. The biological activities of the analogs as antiprotozoals, antifungals and antibacterials were evaluated. The synthetic antibiotics included 3.beta.-acetoxy-4.alpha.-hydroxy-2.beta.-(p-methylbenzyl)pyrrolidine (1b), 3.beta.-acetoxy-2.beta.-benzyl-4.alpha.-hydroxypyrrolidine (1c), 3.beta.-acetoxy-4.alpha.-hydroxy-2.beta.-(m-methoxybenzyl)pyrrolidine (1d), 3.beta.-acetoxy-4.alpha.-hydroxy-2.beta.-(o-methoxybenzyl)pyrrolidine (1e), 3.beta.-acetoxy-4.alpha.-hydroxy-2.beta.-(.alpha.-methyl-p-methoxybenzyl)pyrrolidine (1f) and 3.beta.-acetoxy-4.alpha.-hydroxy-2.beta.-(.alpha.-phenyl-p-methoxybenzyl)pyrrolidine (1g). The anisomycin analogs showed activity against protozoa and fungi, but this activity was restricted primarily to the p-methylbenzyl and benzyl analogs 1b and 1c. The activities dropped dramatically as the methoxy substituent was moved to the meta or ortho positions of the benzyl group (1d and 1e) or a methyl or phenyl group was attached at the .alpha.-benzyl C (1f and 1g).