Synthesis of a phosphinate analogue of the anti-tumour phosphate di-ester perifosine via sequential radical processes

Abstract

An efficient synthesis of a phosphinate analogue of the anti-tumour phosphate di-ester perifosine is described (6 steps and 50% overall yield). The two phosphorus–carbon bonds in the perifosine analogue were prepared by sequential double radical hydrophosphinylation processes. This is the first example of a phosphinate analogue of perifosine, designed to be resistant to hydrolysis by phospholipid-metabolizing enzymes.