ORGANOPHOSPHORUS ANALOGS AND DERIVATIVES OF THE NATURAL L-AMINOCARBOXYLIC ACID AND PEPTIDES .7. ENZYME-SYNTHESIS OF PHOSPHA-C PEPTIDES

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 L-alpha-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.