An efficient synthesis of N-phosphinoylmethylamino acids and some of their derivatives

Abstract

N-Phosphinoylmethylamino acid derivatives 11–18 are obtained in high yield on N-bromomethylation of hexafluoroacetone protected amino acids 1–5 and subsequent Michaelis–Arbusov reaction. The carboxy activated species 11–18 react with a wide range of nucleophiles to give the unprotected N-phosphinoylmethylamino acids 19–22, amides 23–25, peptides 26–28, azapeptide 29 and the hydroxamic acid 30, respectively. The reaction sequence is suitable for generating libraries of N-phosphinoylmethylamino acid derivatives, which represent phosphonoamidate isosteres.