Efficient Asymmetric Synthesis of the Vasopeptidase Inhibitor BMS-189921

• Published in: Organic letters Vol. 5; no. 17; pp. 3155 - 3158
• Main Authors: Singh, Janak, Kronenthal, David R, Schwinden, Mark, Godfrey, Jollie D, Fox, Rita, Vawter, Edward J, Zhang, Bo, Kissick, Thomas P, Patel, Bharat, Mneimne, Omar, Humora, Michael, Papaioannou, Chris G, Szymanski, Walter, Wong, Michael K. Y, Chen, Chien K, Heikes, James E, DiMarco, John D, Qiu, Jun, Deshpande, Rajendra P, Gougoutas, Jack Z, Mueller, Richard H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 21.08.2003; Amer Chemical Soc
• Subjects: Azepines - chemical synthesis; Azepines - chemistry; Azepines - pharmacology; Chemistry; Chemistry, Organic; Endothelium, Vascular - enzymology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Hydrogenation; Neprilysin - antagonists & inhibitors; Physical Sciences; Science & Technology; Stereoisomerism; TRANSFORMATION; ACETYLENE DERIVATIVES; SUBSTITUTION; DYNAMIC RESOLUTION; AMINO-ACIDS; ENANTIOSELECTIVE HYDROGENATION; ESTERS; ARYL; MERCAPTOACYL DIPEPTIDES; HECK REACTION
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol0352308

An efficient asymmetric synthesis of the vasopeptidase inhibitor BMS-189921 was accomplished. Two short enantioselective syntheses of the common key intermediate (S)-α-aminoazepinone 6b were developed. Olefin 3 was converted to 6b via asymmetric hydrogenation. Alternatively, enyne 12 was converted to racemic α-aminoazepinone 15b, which was transformed to 6b by a practical dynamic resolution.