Bisphosphonate prodrugs. Synthesis and identification of (1-hydroxyetrylidene)-1,1-bisphosphonic acid tetraesters by mass spectrometry, NMR spectroscopy and X-ray crystallography

The preparation and identification of symmetric, H3CC(OH)[P(O)(OR)(2)](2), where R=Me, Et, Pr-1, Ph, and non-symmetric, H3CC(OH)[P(O)(OR1)(OR2)][P(O)(OR3)(OR4)], where R-1=Me, R-2=R-3=R-4=Ph; R-1 =R-2=R-3=Ph, R-4=Me; R-1=R-3=Me, R-2=R-4=Ph; R-1=R-2=Et, Pr-1, Ph and R-3=R-4=Me; tetraester derivatives of etidronate h ave been studied. Compounds were prepared from HP(O)(OR1)(OR2) and AcP(O)(O R3)(OR4) species under reflux. Mechanism studies have been made using HP(O) (OCD3)(OPh) and AcP(O)(OMe)(OPh) as starting materials. H-1, C-13, P-31 NMR data and the MS fragmentation data in the gas phase are reported. The soli d-state structures are given for three of the compounds, where R=Et, Ph and R-1=R-2=Ph, R-3=R-4=Me.