A highly efficient method for the preparation of phosphinic pseudodipeptidic blocks suitably protected for solid-phase peptide synthesis

Building blocks of the general type FmocXaaψ{PO(OAd)CH₂}YaaOH suitable for solid-phase synthesis of phosphinic peptides have been prepared using a new synthetic strategy based on mild and high-yielding reactions. The key reaction of this method is the Michael addition of activated Fmoc protected silyl aminophosphonites to benzyl acrylates at room temperature. As compared to our previous work, this method consists of less synthetic steps and doubles the overall yield, thus providing a convenient route to phosphinic synthons suitable for the solid-phase preparation of inhibitors of various metalloproteases.