Stereoisomers of cyclic urea HIV-1 protease inhibitors: Synthesis and binding affinities

We have synthesized stereoisomers of cyclic urea HIV-1 protease inhibitors to study the effect of varying configurations on binding affinities. Four d ifferent synthetic approaches were used to prepare the desired cyclic urea stereoisomers. The original cyclic urea synthesis using amino acid starting materials was used to prepare three isomers. Three additional isomers were prepared by synthetic routes utilizing L-tartaric acid and D-sorbitol as c hiral starting materials. A stereoselective hydroxyl inversion of the cycli c urea trans-diol was used to prepare three additional isomers. In all 9 of the 10 possible cyclic urea stereoisomers were prepared,, and their bindin g affinities are described.