Reference

Application of the Lewis acid-Lewis base bifunctional asymmetric catalysts to pharmaceutical syntheses: stereoselective chiral building block syntheses of human immunodeficiency virus (HIV) protease inhibitor and b3-adrenergic receptor agonist

Application of the Lewis acid-Lewis base bifunctional asymmetric catalysts to pharmaceutical syntheses: stereoselective chiral building block syntheses of human immunodeficiency virus (HIV) protease inhibitor and b3-adrenergic receptor agonist. Nogami, Hiroyuki; Kanai, Motomu; Shibasaki, Masakatsu (Chemicals Development Laboratories, Mitsubishi Rayon Co., Ltd.Chemicals with cas numbers 651309-20-5 and 98760-08-8 also play role., Kanagawa 230-0053, Japan). Chemical & Pharmaceutical Bulletin, 51(6), 702-709 (English) 2003 Pharmaceutical Society of Japan. CODEN: CPBTAL. ISSN: 0009-2363. DOCUMENT TYPE: Journal CA Section: 34 (Amino Acids, Peptides, and Proteins) Section cross-reference(s): 1 Chiral building block syntheses of promising drugs were achieved using two types of catalytic stereoselective cyanosilylations of aldehydes promoted by Lewis acid-Lewis base bifunctional catalysts (e.g., I) as the key steps (diastereoselective cyanosilylation of amino aldehyde and enantioselective cyanosilylation). In the first part of this article, syntheses of chiral building block II (Boc = tert-butoxycarbonyl) of Atazanavir [human immunodeficiency virus (HIV) protease inhibitor] using the bifunctional catalyst I are discussed. The reaction of Boc-protected phenylalaninal in the presence of 1 mol % catalyst I selectively afforded the anti isomer III as the major product (diastereomeric ratio = ), which was successively converted to the corresponding epoxide II in six steps. In the second part, we describe a chiral building block synthesis of b3-adrenergic receptor agonists. The enantioselective cyanosilylation of 3-chlorobenzaldehyde with 9 mol % catalyst I gave the chiral cyanohydrin, which was converted to (R)-2-(3-chlorophenyl)-2-hydroxyethylamine by redn. Moreover, the chiral ligand of catalyst I could be recovered without column chromatog. and reused without decreasing its activity. .