PEPTIDE INHIBITORS OF ASPARTIC PROTEINASES WITH HYDROXYETHYLENE ISOSTERE REPLACEMENT OF PEPTIDE-BOND - II - PREPARATION OF PSEUDOTETRAPEPTIDES DERIVED FROM DIASTEREOISOMERIC 5-AMINO-2-BENZYL-4-HYDROXY-6-PHENYLHEXANOIC ACIDS

Twelve pseudotetrapeptides, Boc-NHCH(CH2Ph)CH(OH)CH2CH(CH2Ph) CO-Xaa-P he-NH2 9-11, were prepared by nzotriazol-1-yl)oxy]tris(dimethylamino)p hosphonium hexafluorophosphate-mediated couplings of diastereoisomeric O-silylated (2R or 2S,4R or rt-butoxycarbonyl)amino-4-hydroxy-6-pheny lhexanoic acids 1 with dipeptides H-Xaa-Phe-NH2 (Xaa = Gln, Glu(OBzl) or Ile) 3-5, followed by O-deprotection. Pseudotetrapeptides 9-11 were tested for inhibition of aspartic proteinases secreted by Candida alb icans and C. tropicalis. The level of inhibition of both yeast protein ases was very low, contrasting with the nanomolar IC50 values obtained for inhibition of HIV-1 proteinase.