A Process in Need Is a Process Indeed: Scalable Enantioselective Synthesis of Chiral Compounds for the Pharmaceutical Industry

This report deals with enantioselective synthesis of viracept 1 (nelfinavir mesylate, AG 1343), a potent HIV protease inhibitor, and 3‐hydroxytetradecanoic acid 3 , a component of lipid A comprising lipopolysaccharide embedded in the cell surface of Gram‐negative bacteria, from both strategic and practical perspectives. As regards the synthesis of 1 , the synthetic approaches to its central intermediate 2 possessing the common structural motif of 1,4‐differentially substituted‐2‐amino‐3‐hydroxylbutane are mainly discussed with emphasis on the molecular symmetry that has helped streamline the synthetic strategy. In the discussion of the synthetic strategies to access a single enantiomer of 3 , the chiral methodologies that have been applied so far are assessed for industrial viability; the synthetic alternatives explored include resolution via diastereomeric salt formation, lipase‐catalyzed kinetic resolution, asymmetric synthesis, and chiral pool approaches.