Organophosphorus analogues and derivatives of the natural l-aminocarboxylic acid and peptides vii. Enzyme synthesis of phospha-c peptides

Abstract

It is proved that the phospha-C peptides (with PO NH instead of CO NH bond) can be obtained by enzyme-catalyzed condensation of esters of alkylphosphonic and dialkylphosphinic acids with esters of Lα-aminocarboxylic acids. Condensations of the natural phosphono-, methylphosphino esters 1– 4 and the ethyl esters of glycine, L-alanine, L-methionine, and L-histidine were carried out in the presence of alkaline phosphatase (with the esters 1 and 2) and phosphodiesterase I (with the esters 3 and 4) to give the phospha-C peptides 5–20, respectively. The synthesis of the free dipeptides 21– 36 was achieved by hydrolysis of the protecting groups using total bee venom. A similar procedure applied to the dipeptides 37 and 38 (obtained by selective hydrolysis with the enzyme catalyst alkaline mesintericopeptidase of N-acetyl group of 9 and 17) and the phosphino component 4 yielded the phospha-C tripeptides 39– 42, and with glycine anhydride to tetrapeptides 43 and 44, respectively.