A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690.
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.
Fors
Kristina S.
KS
Chemical Process Research & Preparations, 1510-91-2, Pharmacia & Upjohn Inc., 7000 Portage Road, Kalamazoo, Michigan 49001.
Gage
James R.
JR
Heier
Richard F.
RF
Kelly
Robert C.
RC
Perrault
William R.
WR
Wicnienski
Nancy
N