Synthesis of biologically active phosphonates

Abstract

Organophosphorous compounds have been extensively studied because of their biochemical importance. The synthesis and characterization of some ethyl p-nitrophenyl arene-phosphonates acting as brain cholinesterase inhibitors; called “suicide targets”, are described. The reluctance of aromatic halides to participate in Arbuzov reaction when it is treated with triethylphosphite is overcome by an efficient nickel chloride catalyst. Diethylphosphonates obtained were easily converted into the ethylchlorophosphonate reactive intermediates by refluxing in oxalyl chloride. Substitution of the chlorine atom by a p-nitrophenoxy group afforded biologically active dissymmetric phosphonates. Many ethyl-p-nitrophenyl arenephosphonates have been synthesized in that way with good yields and characterized by the usual spectroscopic methods. When the phosphonate is incubated in an appropriate physiological medium, enzyme inhibition occurs with release of p-nitrophenol the fluorescence appeared then indicating the binding enzyme-inhibitor.

Keywords

• phosphonate synthesis
• colinesterase inhibitors
• suicide targets
• fluorescence