A CONVERGENT, SCALABLE SYNTHESIS OF HIV PROTEASE INHIBITOR PNU-140690

PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinica l evalution as a chemotherapeutic agent for treatment of AIDS, was syn thesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of ni troaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of e nantiomers. Intermediates along the synthetic routes were chosen to ma ximize opportunities for isolation and purification by crystallization .