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 ( 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.