PROTECTION OF THE HYDROXYPHOSPHINYL FUNCTION OF PHOSPHINIC DIPEPTIDESBY ADAMANTYL - APPLICATION TO THE SOLID-PHASE SYNTHESIS OF PHOSPHINICPEPTIDES

To develop solid-phase synthesis of phosphinic peptides, different Fmo cXaa Psi{PO(OAd)CH2}XaaOH building blocks have been prepared, where Fm oc is (fluorenylmethoxy)carbonyl. In this respect, the protection of t he hydroxyphosphinyl function in these phosphinic dipeptides by the ad amantyl group turns out to be convenient. The phosphinic adamantyl est ers are completely stable in basic conditions and can be removed under relatively mild acidic conditions. Using these building blocks, despi te the bulkiness of the adamantyl group, no particular problem of coup ling was observed during the solid-phase synthesis of phosphinic pepti des by the Fmoc strategy. The developed methodology is of particular i nterest to facilitate the development of potent inhibitors of zinc-met alloproteases.