Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 20, 2018
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Kalihinol C (Shenvi), Lepadin B (Chen), Stachyflin (Magauer), Antrocin (Su/Yang), Wickerol A (Trauner), Morphine (Chen)

The isocyanoterpenes, represented by kalihinol C (4), show remarkable activity against Plasmodium falciparum. Ryan A. Shenvi of Scripps/La Jolla described a synthesis of 4 centered on the next chapter in his development of dendralene sequential Diels-Alder cycloadditions, assembling 3 by combining 1 with 2 (J. Am. Chem. Soc. 2017, 139, 3647. DOI: 10.1021/jacs.7b01124).

The alkaloid (-)-lepadin B (8) is a potent blocker of certain nicotinic acetylcholine receptors. En route to 8, Xiaochuan Chen of Sichuan University observed remarkable diastereoselectivity in the Diels-Alder cycloaddition of 5 with 6 to give 7 (Org. Lett. 2017, 19, 5372. DOI: 10.1021/acs.orglett.7b02647).

The meroterpenoids, represented by (-)-stachyflin (12), show significant activity against methicillin-resistant Staphylococcus aureus. Thomas Magauer of the University of Innsbruck developed a general route to this class of natural products, preparing the key intermediate 11 by combining the chirons 9 and 10 (Nature Commun. 2017, 8, 2083. DOI: 10.1038/s41467-017-02061-7).

(-)-Antrocin, isolated from a fungus that grows on the Niu-Zarng tree, shows activity against MDA-MB-231 breast cancer cells. In the course of a synthesis of (+)-antrocin (15), Ming-Der Su of the National Chiayi University and Te-Fang Yang of the National Chi Nan University achieved remarkable diastereoselectivity in the cyclization of the camphanate 13 to 14 (J. Org. Chem. 2017, 82, 9576. DOI: 10.1021/acs.joc.7b01600).

Wickerol A (19), isolated from the fungus Trichoderma atroviride FK1-3849, shows potent activity against type A/H1N1 influenza virus. Dirk Trauner of the Ludwig-Maximilian University Munich found that the Diels-Alder cyclization of 16 with the sensitive diene 17 to give 18 was best promoted by the catalyst combination developed by Jung (J. Am. Chem. Soc. 2017, 139, 9491. DOI: 10.1021/jacs.7b05046).

David Y.-K. Chen of Seoul National University oxidized the phenol 20 to a triene, that cyclized to 21. The alkene bridge of 21 was then oxidized, leading to the morphinans, including morphine (22) (Chem. Sci. 2017, 8, 7031. DOI: 10.1039/C7SC03189K).

D. F. Taber, Org. Chem. Highlights 2018, August 20.