2-(acyloxy)ethylphosphonate analogues of prenyl pyrophosphates: Synthesis and biological characterization

2-(Acyloxy)ethylphosphonate analogues of geranyl, farnesyl, and geranylgera nyl pyrophosphate have been prepared. Horner-Wadsworth-Emmons condensation of different terpene aldehydes with an unsymmetrical bisphosphonate was the key step in syntheses of the phosphonates bearing a,P-unsaturated acyloxy groups. After preparation of the respective phosphonic acids through reacti on with TMSBr, both acids and esters were tested for their effects on DNA s ynthesis in human-derived myeloid and lymphoid leukemia cell lines. The pho sphonate esters varied substantially in their ability to impair proliferati on of the different cell lines, but testing against one possible target, fa rnesyl protein transferase (FPTase), revealed little impact at concentratio ns ranging up to 10 muM. Because the corresponding 2,3-dihydro compounds sh owed similar biological activity, conjugate addition would not appear to be involved in the toxicity. (C) 2000 Elsevier Science Ltd. All rights reserv ed.