Stereoselective synthesis of non symetric dihydroxyethylene dipeptide isosteres via epoxyalcohols derived from α-amino acids

C2 symmetric and non-symmetric pseudopeptide inhibitors of HIV-1 protease, containing a S,S,S,S-diaminodiol isostere have been obtained by a synthetic strategy designed to couple a high degree of stereochemical control with complete flexibility in the choice of residues in the central core and flanking chains. Using this approach, inhibitors with IC50 values in the low nanomolar range were assembled from readily available aminoacids and carboxylic acids, chosen with the aid of molecular modelling.