Simple cis-epoxide-based inhibitors of HIV-1 protease

The 4-nitrophenoxy-based epoxide 6a, conveniently synthesized using Sharpless epoxidation chemistry, has been shown to be an irreversible inhibitor of HIV-1 protease (Kinact 1.8 μM, pH 6.5, I = 0.1 M). Related analogues, differing in the mode of attachment to the epoxide core, have also been prepared and assayed against HIV-1 protease.