Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 21, 2022
Douglass F. Taber
University of Delaware

Alkaloid Synthesis: Aristoquinoline (Reber), Hinckdentine A (Su/Hong), Madangamine E (Hamlin/Dixon), Normacusine B (Xue/Qin), Daphenylline (Lu), Arboridine (Ma)

Aristoquinoline (2), isolated from the leaves of the Maqui tree Aristotelia chilensis, was found to be a nicotinic acetylcholine receptor antagonist. Keith P. Reber of Towson University assembled 2 by a Bischler-Napieralski type cyclization of the activated amide 1, followed by reduction (Synthesis 2022, 54, 1404. DOI: 10.1055/s-0041-1737276).

Hinckdentine A (5) was isolated from the bryozoan Hincksinoflustra denticulata collected on the eastern coast of Tasmania. En route to 5, Zhishan Su of Sichuan University and Ran Hong of the Shanghai Institute of Organic Chemistry effected the ring expansion of the cyclohexenone 3 to the lactam 4 (JACS Au 2022, 2, 793. DOI: 10.1021/jacsau.2c00048).

Madangamine E (8) is one of several alkaloids isolated from the marine sponge Xestospongia ingens van Soest. Trevor A. Hamlin of the Vrije Universiteit Amsterdam and Darren J. Dixon of the University of Oxford showed that a highly enantioselective thiourea-catalyzed intramolecular Michael cyclization of the nitroalkene 6 to the ketone 7 enabled the asymmetric total synthesis of 8 (J. Am. Chem. Soc. 2022, 144, 1407. DOI: 10.1021/jacs.1c12040).

Normacusine B (11), also known as vellosiminol, is a hypotensive alkaloid isolated from the root of Strychnos atlantica. Fei Xue and Yong Qin, also of Sichuan University, established the second piperidine ring of 11 by the Ti-mediated oxidative cyclization of the amide 9 to the diol 10 (Org. Lett. 2022, 24, 3515. DOI: 10.1021/acs.orglett.2c01177).

Daphenylline (14) is one of a variety of the several related alkaloids isolated from the genus Daphniphyllum, evergreen shrubs and trees of east and southeast Asia long used in medicinal chemistry. A key step in the total synthesis of 14 described by Hai-Hua Lu of Westlake University is the diastereoselective double reductive amination of the keto aldehyde 12, that was followed by spontaneous cyclization to the lactam 13 (J. Am. Chem. Soc. 2022, 144, 5750. DOI: 10.1021/jacs.2c01674).

Arboridine (17) was isolated from a Malaysian Kopsia species. Zhiqiang Ma of South China University of Technology assembled the pentacyclic intermediate 16 by the double intramolecular Mannich cyclization of 15 (J. Org. Chem. 2022, 87, 8223. DOI: 10.1021/acs.joc.2c00602).

D. F. Taber, Org. Chem. Highlights 2022, November 21.