PYRIDOXAL PHOSPHATE .I. PHOSPHONIC ACID ANALOGS OF PYRIDOXAL PHOSPHATE . SYNTHESIS VIA WITTIG REACTIONS AND ENZYMIC EVALUATION

Phosphonic acid analogs (4-7) of pyridoxal (1) and pyridoxol (2) phosphates, in which the ester oxygens of 1 and 2 have been replaced by CH2 (4 and 5) and CH (6 and 7) units, have been synthesized conveniently through the phosphonate modification of the Wittig reaction. Thus, condensation of tetraethyl methyienediphosphonate (9) and α4,3-O-isopropylideneisopyridoxal (8) gave 2-[2,2,8-trimethyl-5-(4H-m-dioxmo[4,5-c]pyridyl)]ethenylphosphonate (10), a reaction in which the phosphorus function and the carbon unit designed to replace the ester oxygen of 1 and 2 have been introduced simultaneously. The key intermediate 10 was converted through standard reactions into 4-7. Enzymic evaluation of 4-7 showed them to possess inhibitory, but not catalytic, properties. On aspartate aminotransferase the ethenylphosphonates 6 and 7 were more inhibitory than the ethylphosphonates 4 and 5 and were approximately as inhibitory as the phosphate monoester, pyridoxol phosphate (2). On tyrosine decarboxylase the saturated acids 4 and 5 were the more inhibitory but were much less so than 2. Thus, in some biological systems, phosphate monoesters may be effectively simulated by phosphonic acid analogs which contain a carbon unit replacing the ester oxygen in the parent phosphate monoester. © 1969, American Chemical Society. All rights reserved.