A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690
The Journal of Organic Chemistry1998Vol. 63(21), pp. 7348–7356
Citations Over TimeTop 22% of 1998 papers
Kristina S. Fors, James R. Gage, Richard F. Heier, Robert C. Kelly, William R. Perrault, Nancy A. Wicnienski
Abstract
PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.
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