A New, Efficient, Two Step Procedure for the Preparation of the Antineoplastic Agent Sparfosic Acid

Abstract

Sparfosic acid can easily be prepared in two steps and in excellent yield from condensation of the commercially available starting materials L-aspartic acid di-tert-butyl ester hydrochloride and diethylphosphonoacetic acid, followed by a quadruple deprotection of acidic functions under mild conditions using bromotrimethylsilane.

Notes

The exception to this is ref. 6e.

For example see ref. 1, 6e, 7a-c.

This is opposed to the instability of alternative acid labile trimethylsilyl esters protection groups employed throughout the methodology of Stiebitz et al.^6e whereupon purification by distillation or anhydrous chromatography became obligatory.

Following results from a kinetic study, the reaction was left for 6h at rt. The mixture was then concentrated, hydrolysed and lyophilysed, and resulting composition analysed by ¹H NMR and reverse phase HPLC analysis.