STEREOSELECTIVE SYNTHESIS OF HIV-1 PROTEASE INHIBITOR, DMP-323

DMP 323, a potent HIV-1 protease inhibitor, has been synthesized by an efficient stereoselective process, amenable to large scale preparatio ns. The core C-2 symmetric diol was synthesized by a stereoselective p inacol coupling of CBZ protected D-phenylalanine. Judicious selection of protecting groups allowed cyclic urea formation under mild conditio ns, enhanced the ease of bis-alkylation, and led to intermediates whic h were easily purified without chromatography. Additionally, a one-pot , high yield process was developed to prepare the alkylating agent, 4- [(triphenylmethoxy)methyl]benzyl chloride from 1,4-benzenedimethanol.