Organic Chemistry Portal
Organic Chemistry Highlights

Monday, October 31, 2016
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Coccoline (Kurkin), Decrusivine (Xia), Grandilodine C (Nishida), Lycopalhine A (Trauner), Daphenylline (Yokoshima/Fukuyama), Communesin F (Movassaghi)

Erythrina alkaloids, represented by coccoline (3), display a wide range of, interalia, CNS activity. Alexander V. Kurkin of Lomonosov Moscow State University devised (Chem. Eur. J. 2016, 22, 7262. DOI: 10.1002/chem.201600273) a simple route to the Erythrina skeleton, cyclizing the product from the bromination of 1 to the amide 2.

Decrusivine (6), isolated from the Creeping Philodendron Raphidophora decursiva, shows significant anti-malaria activity. Chengfeng Xia of the Kunming Institute of Botany observed (Org. Lett. 2016, 18, 1474. DOI: 10.1021/acs.orglett.6b00417) high diastereoselectivity in the oxidative cyclization of 4 to 5.

Grandilodine C (9), isolated from Kopsia grandiflora of the Anambas Islands, has three quaternary stereogenic centers. Atsushi Nishida of Chiba University showed (Angew. Chem. Int. Ed. 2016, 55, 3473. DOI: 10.1002/anie.201510561) that the critical third quaternary center of 8 could be constructed by the π-allyl Pd cyclization of the reduction product from 7.

Lycopalhine A (13) was isolated from the staghorn clubmoss Palhinhaea cernua, widely used in traditional medicine. En route to 13, Dirk Trauner of the Ludwig-Maximilian-Universität München found (Angew. Chem. Int. Ed. 2016, 55, 2191. DOI: 10.1002/anie.201509602) that L-proline was effective in mediating the intramolecular Mannich condensation of the imine derived from the combination of 10 and 11, to give 12. Rexyn-300, a commercial resin that contains both strong acid and strong base groups, has also been shown (Stereoselective Construction of Nitrogen Heterocycles 2006, April 14) to be effective at mediating such cyclizations.

Daphenylline (16), isolated in 2009, is the first Daphniphyllum alkaloid with a benzene ring in the core structure. As Satoshi Yokoshima and Tohru Fukuyama of Nagoya University had predicted (Angew. Chem. Int. Ed. 2016, 55, 6067. DOI: 10.1002/anie.201601958), intramolecular dipolar cycloaddition of the azomethine ylide derived from 14 delivered 15 with high diastereocontrol.

There are many indole-derived alkaloids, as exemplified by communensin F (19), that are produced biosynthetically by the heterodimerization of simpler, unlike alkaloids. Mohammad Movassaghi of MIT developed (J. Am. Chem. Soc. 2016, 138, 7763. DOI: 10.1021/jacs.6b04072) a protocol for the chemical replication of this dimerization, oxidizing the sulfamide 17 to the diazene (not illustrated), followed by photochemical coupling to 18.

D. F. Taber, Org. Chem. Highlights 2016, October 31.