Synthesis of pyrophosphonic acid analogues of farnesyl pyrophosphate

The synthesis of four new analogues (i.e. 3-6) of farnesyl pyrophosphate (FPP), which may function as inhibitor of squalene synthase, is described. Compounds 3 and 4 were readily accessible by reaction of farnesal with diethyl phosphite or dimethyl lithiomethylphosphonate, respectively, followed by condensation of the resulting alcohols with diethyl phosphonomethyl triflate. The preparation of 5 and 6 was accomplished by alkylation of bis(diethyl phosphonomethyl) ether or tetraethyl methylenebisphosphonate, respectively, with farnesyl bromide.