Phosphonate monoesters and method of preparation

Chemistry of carbon compounds – Dipeptides – e.g. – aspartame – anserine – carnosine – etc.

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1951035R, 260958, 260961, 260973, 260983, 260987, 260990, C07F 940

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040411117

ABSTRACT:
Synthesis of phosphonate monoesters, as well as the use of such monoesters as substrates for enzymes which normally hydrolyze phosphodiester linkages, and a method for distinguishing between Type I and Type II phosphodiesterase enzymes using such monoesters as substrates are disclosed herein. Monoesters of phosphonic acids are prepared by the displacement of chloride from an appropriate phosphonic acid dichloride by a phenol or alcohol with pyridine as the solvent, reacting the same and then removing the solvent, after which the remaining ester chloride and dichloride are hydrolyzed by addition of water. The acid and ester are then separated and the acid-free ester is taken up in a polar organic solvent and precipitated as a salt by the addition of aqueous base, with the product then being filtered, washed with fresh acetone, dried and then stored until needed. The thus formed phosphonate monoesters are shown to be effective for use as substrate for phosphodiesterase of the Type I specificity and are shown to be ineffective for use as substrates for phosphodiesterase of the Type II specificity. The type of phosphodiesterase is therefore determined by the amount of activity against phosphonate monoesters.

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