Synthesis and evaluation of new 4-phospho-d-erythronic acid derivatives as competitive inhibitors of spinach ribose-5-phosphate isomerase

This paper reports the synthesis of new 4-phospho-d-erythronic acid derivatives, namely 4-phospho-d-erythronohydroxamic acid (1), 4-phospho-d-erythronohydrazide (2), and 4-phospho-d-erythronamide (3), and their kinetic evaluation as new competitive inhibitors of the isomerization reaction between d-ribose 5-phosphate and d-ribulose 5-phosphate catalyzed by spinach ribose-5-phosphate isomerase (RPI). By comparison to the only known RPI inhibitor, 4-phospho-d-erythronate (4, Ki=28 μM, Km/Ki=270), the hydroxamic acid 1, obtained by an eight-step synthesis from d-arabinose, appears as a new potent high-energy intermediate analogue inhibitor of the isomerization reaction (Ki=29 μM, Km/Ki=260).