Synthesis of Antimicrobial N-Phthaloyl-alanyl-derived Amidophosphates and Triazoles

Abstract

N-Phthaloyl-alanylazide reacts smoothly with trialkyl phosphites producing the corresponding α- aminophosphates. With dialkyl hydrogenphosphonates in the presence of benzoyl peroxide, amidophosphates were the isolated products whereas the oxoaziridin-1-yl-phosphonic diamide was preferentially provided from the reaction of the azide with tris(dimethylamino)phosphine. The azide was also allowed to react with α-keto-, α-ethoxycarbonyl- and α-cyanomethylenetriphenylphosphorane to give the corresponding linear disubstituted 1,2,3-triazoles. Screening results of antibiotic potency for the products were discussed in terms of structure-activity relationship (SAR), and an attempt was made to define the structural features for lead compounds.