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.
Ikunaka
Masaya
M
Chief Scientist, Research & Development Center Nagase & Co., Ltd. 2-2-3 Murotani, Nishi-ku, Kobe, 651-2241, Japan. masaya.ikunaka@nagase.co.jp
D002384:Catalysis; D006090:Gram-Negative Bacteria / Q000737:chemistry; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008049:Lipase / Q000378:metabolism; D008050:Lipid A / Q000737:chemistry; D015394:Molecular Structure; D009227:Myristic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D019888:Nelfinavir / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D017320:HIV Protease Inhibitors; D008050:Lipid A; D009227:Myristic Acids; C009893:beta-hydroxymyristic acid; D008049:Lipase; D019888:Nelfinavir