Nitrile Containing Bisphosphonates: Easy Synthesis through Metal Catalyzed Michael Addition

New nitrile-containing gem-bisphosphonates as drug candidates for the contrast of osteoporosis are presented, their synthesis being based on the metal catalyzed Michael conjugate addition of trimethylsilyl cyanide to unsaturated bisphosphonate precursors. Zn(OTf)(2) turned out to be the most efficient metal catalyst for the reaction enabling the formation of beta-nitrile substituted bisphosphonates in good yields. The corresponding final bisphosphonic acids bearing the nitrile moiety were obtained by deprotection of the ethyl ester moiety. They showed aggregation properties in water due to their amphiphilic nature and will be evaluated in order to assess their biological anti-osteoclast activity.