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

Building blocks of the general type FmocXaa Psi {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 protecte d silyl aminophosphonites to benzyl acrylates at room temperature. As compa red 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. (C) 2001 Elsevier Science Ltd. All rights reserved.