Asymmetric synthesis of the potent HIV-protease inhibitor, nelfinavir.

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.