A Convergent Total Synthesis of the Michellamines

• Published in: Journal of organic chemistry Vol. 63; no. 4; pp. 1090 - 1097
• Main Authors: Bringmann, Gerhard, Götz, Roland, Keller, Paul A, Walter, Rainer, Boyd, Michael R, Lang, Fengrui, Garcia, Alberto, Walsh, John J, Tellitu, Imanol, Bhaskar, K. Vijaya, Kelly, T. Ross
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.02.1998; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Physical Sciences; Science & Technology; ANCISTROCLADUS-KORUPENSIS; ACETOGENIC ISOQUINOLINE ALKALOIDS; CROSS-COUPLING REACTION; ACIDS; A-C; ESTERS; HALOARENES; BIARYLS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo971495m

A convergent total synthesis of the anti-HIV michellamines (1) is described. The tetraaryl skeleton of the michellamines was constructed by formation first of the inner (nonstereogenic) biaryl axis and subsequently of the two other (stereogenic) axes in a highly convergent manner. The key transformation features a double Suzuki-type cross-coupling reaction between binaphthalene ditriflate 26 and isoquinolineboronic acid 35. Ditriflate 26 is synthesized in six steps starting from diene 6 and 2,6-dibromobenzoquinone (9) in 21% overall yield. For large scale production of 26, a substantially shortened version of an existing procedure for the preparation of bisnaphthoquinone 13 was also developed, which allows for the preparation of 13 from benzoquinone and diene 6 in five steps and 67% overall yield. Binaphthoquinone 13 was subsequently converted into ditriflate 26 in three steps and 67% overall yield. By the described synthetic strategy, michellamines A (1a) and B (1b) are produced (1a:1b = 1:2.5) in 24.6% overall yield from diene 6. Curiously, none of the nonnaturally occurring atropoisomer 1c is formed.