Stereoselective synthesis of 1-aminoalkanephosphonic acids with two chiral centers and their activity towards leucine aminopeptidase

Abstract

The stereoselective synthesis of 1-amino-2-alkylalkanephosphonic acids, namely, compounds bearing two chiral centers, was achieved by the condensation of hypophosphorous acid salts of (R)(+) or (S)(-)-N-alpha-methylbenzylamine with the appropriate aldehydes in isopropanol. Simultaneous deprotection and oxidation by the action of bromine water provided equimolar mixtures of the RS:RR and SR:SS diastereomers of desired acids. They appeared to act as moderate inhibitors of kidney leucine aminopeptidase with potency dependent on the absolute configuration of both centers of chirality.