Abstract: Synthesis of (1-acyloxyethylidene)-1,1-bisphosphonicacids, where the acyl group is decanoyl ( 1a ), lauroyl ( 1b ), palmitoyl( 1c ), stearoyl ( 1d ) or oleoyl ( 1e ) have been described. Preparationof (1-oleoyloxyethylidene)-1,1-bisphosphonic acid tetramethyl es-ter ( 2 ) and its P , P ¢-dimethyl ester (disodium salt 3 and acid form 4 )in multigram scale has also been reported. Solubility of 1e in organ-ic solvents and water was tested. Key words: bisphosphonate, etidronate, fatty acids, synthesis, pro-drug Bisphosphonates (BPs) are analogs of naturally occurringpyrophosphate and are used as drugs for the treatment ofvarious bone diseases, like osteoporosis. 1 Etidronate, (1-hydroxyethylidene)-1,1-bisphosphonic acid (HEBPA) di-sodium salt is one example of a BP compound (Figure 1).BPs have been used for decades as drugs for the treatmentof various bone diseases, but recently these compoundswere found to be active in many other fields, like parasiticdiseases 2 and atherosclerosis.