Synthesis and kinetic evaluation of 4-deoxy-4-phosphonomethyl-D-erythronate, the first hydrolytically stable and potent competitive inhibitor of ribose-5-phosphate isomerase

4-deoxy-4-Phosphonomethyl-D-erythronate, an isosteric and hydrolytically stable analogue of the known ribose-5-phosphate isomerase inhibitor 4-deoxy-4-phospho-D-erythronate, was obtained by a 14-step synthesis from D-arabinose through a phosphate isomerase inhibitor 4-deoxy-4-D-erythronate, was obtained by a 14-step synthesis from D-arabinose through a highly improved Synthesis of the precursor 5-deoxy-5-phosphonomethyl-D-arabinose. The title compound appears as the first stable and potent competitive inhibitor of the enzyme catalyzed isomerization of ribose-5-phosphate to D-ribulose-5-phosphate (K-i = 74 muM. K-m/K-i = 100). exhibiting only a 3-fold weaker inhibitory activity than its phosphate analogue. (C) 2004 Elsevier Ltd. All rights reserved.