Calix[4]arene-α-hydroxyphosphonic acids. Synthesis, stereochemistry, and inhibition of glutathione S-transferase

Abstract

A series of dipropoxy-, tripropoxy-and tetrapropoxycalix [4]arenes bearing one or two fragments of -hydroxymethylphosphonic acid at the upper rim of the macrocycle was prepared by the reaction of the corresponding mono-and di-formylcalixarenes with sodium salts of dialkyl phosphites or with trialkyl (tristrimethylsilyl)phosphites followed by dealkylation (desilylation) of the ester derivatives. The conformations of the macrocyclic skeleton and the stereoisomeric forms of the compounds obtained were investigated by 1 H NMR. The resulting hydroxymethylphosphonic acids were found to be able to inhibit the activity of glutathione Stransferase in vitro.