Michael J. Sparkes

rac-3,4-DIHYDROXYBUTYLARSONIC ACID: A KEY INTERMEDIATE FOR ISOSTERIC ARSONOLIPIDS

Abstract Synthetic routes starting from 4-bromobut-1-ene and leading to rac-3,4-dihydroxybutylarsonic acid and diphenyl rac-3,4-dihydroxybutyldithioarsonite were explored. All of them gave overall yields 5–16%. Some properties of the free acid and its dilithium salt are described.

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

Acylphosphonic acids, R-CO-PO(OH)2, have been synthesized by the steps [formula: see text] 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 stearothermophilus. The inhibition was competitive with pyruvate, with Ki of 6 microM for the E. coli enzyme (pyruvate Km 0.5 mM) and one of 0.4 mM of the B. stearothermophilus enzyme (pyruvate Km 0.1 mM). Acetylphosphonate and its monomethyl ester are substates for pig heart lactate dehydrogenase, with Km values of 15 mM and 10 mM respectively (pyruvate Km 0.05 mM) and specificity constants one thousandth that for pyruvate.

Improved conditions for the removal of 2-oxoacyl groups from the N-terminus of proteins

Proteins with R-CO-CO-NH- at the N-terminus, rather than the usual R-CH(-NH3+)-CO-NH-, are produced by non-enzymic transamination and also occur in the pyruvoyl enzymes. The oxoacyl group may be specifically removed from a model peptide, in yields of 70-80%, by treating them in 0.1 M phosphate buffer at 37 degreesC for 24 h with 25 mM of the N-phosphonomethyl derivative of phenylene-1,2-diamine. This provides mild conditions for the stepwise removal of N-terminal residues without denaturation.