Abstract

5-Deoxy-5-phospho-D-ribonohydroxamic acid, a mimic of the 1,2-cis-enediolate high-energy intermediate species of the allose-6-phosphate isomerase reaction, was obtained by a six-step synthesis from D-erythronolactone. In contrast to the known competitive ribose-5-phosphate isomerase (Rpi) inhibitors 4-deoxy-4-phospho-D-crythronohydroxamic acid, 4-deoxy-4-phospho-D-erythronate, and 4-deoxy-4-phosphonomethyl-D-erythronate, the new hydroxamic acid selectively inhibits Mycobacterium tuberculosis RpiB (K-i = 0.40 mM, K-m/K-i = 4.5) versus Spinacia oleracea RpiA, and hence appears as a promising lead for the design of potent species-specific inhibitors of the bacterial enzyme. © 2005 Elsevier Ltd. All rights reserved

Published in

Tetrahedron Letters
2005, volume: 46, number: 21, pages: 3691-3694
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

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