A Synthesis of Acylphosphonic Acids and of 1-Aminoalkylphosphonic Acids: The Action of Pyruvate Dehydrogenase and Lactate Dehydrogenase on Acetylphosphonic Acid

Abstract

Acylphosphonic acids, R-CO-PO(OH)₂, have been synthesized by the steps R-CO-C1 R-CO- PO(OMe)₂ R-CO-PO(OMe)-O R-CO-PO(OH)-O^- of which the last is new and provides a mild method for de-esterifying acylphosphonic acids. Their reductive amination gives a simple way of making 1-aminoalkylphosphonic acids. Acetylphosphonic acid inhibited NAD⁺ reduction by pyruvate with the pyruvate dehydrogenases from Escherichia coli and Bacillus slearolhermophilus. The inhibition was competitive with pyruvate, with K₁ of 6 μM for the E. coli enzyme (pyruvate K_m 0.5 mM) and one of 0.4mM fo the B. slearolhermophilus enzyme (pyruvate K_m 0.1 mM). Acetylphosphonate and its monomethyl ester are substates for pig heart lactate dehydrogenase, with K_m values of 15mM and 10mM respectively (pyruvate K_m 0.05 mM) and specificity constants one thousandth that for pyruvate.

Key Words: :

• Pyruvate dehydrogenase
• lactate dehydrogenase
• acetylphophonate
• acylphosphonate
• aminoalkylphosphonate