Asymmetric Synthesis of the Potent HIV-Protease Inhibitor, Nelfinavir

• DOI: 10.1021/jo902048t
• Publication Date: 2009-12-14T14:39:26Z
• Authors: Sadagopan Raghavan; V. Krishnaiah; B. Sridhar
• Keywords: Nelfinavir; Molecular Structure; Stereoisomerism; HIV Protease Inhibitors; 01 natural sciences; Catalysis; 3. Good health; 0104 chemical sciences

An asymmetric synthesis of nelfinavir is described starting from acrolein and (S)-methyl phenyl sulfoxide. The key features include (a) stereoselective preparation of a beta-protected amino-gamma,delta-unsaturated sulfoxide by the reaction of an alpha-sulfinyl carbanion with an unsaturated t-butyl sulfinylimine, (b) stereoselective bromohydrin formation using the pendant sulfoxide group as an intramolecular nucleophile, and (c) use of commercially or readily prepared inexpensive starting materials.