Total synthesis of a pepstatin analog incorporating two trifluoromethyl hydroxymethylene isosteres (Tfm-GABOB) and evaluation of Tfm-GABOB containing peptides as inhibitors of HIV-1 protease and MMP-9

We describe the asymmetric total synthesis of a trifluoromethyl (Tfm) analogue of the aspartate protease inhibitor pepstatin incorporating two gamma-Tfm-gamma-amino-beta-hydroxybutyric acid (gamma-Tfm-GABOB) units instead of the natural statine units. The title compound as well as several Tfm-substituted precursors were tested as inhibitors of HIV-1 protease and Gelatinase B (MMP-9) © 2001 Elsevier Science Ltd. All rights reserved.