Organic Chemistry Portal
Organic Chemistry Highlights

Monday, December 25, 2023
Douglass F. Taber
University of Delaware

Other Methods for C-C Ring Construction: Scabrolide A (Sarlah), Clovan-2,9-dione (Newhouse), Gibberellin A18 (Dai), Isoneoamphilectane (Vanderwal), Stelletin E (Jiao/Xie), Puberuline C (Inoue)

Scabrolide A (3), isolated from the soft coral Sinularia scabra, has both anticancer and anti-inflammatory activity. En route to 3, David Sarlah of the University of Illinois cyclized the enone 1 to the lactone 2 (J. Am. Chem. Soc. 2023, 145, 8805. DOI: 10.1021/jacs.3c02317).

Based on computational analysis, Timothy R. Newhouse of Yale University anticipated the successful free-radical cyclization of the selenide 4 to clovan-2,9-dione (5) (Nature Synth. 2023, 2, 527. DOI: 10.1038/s44160-023-00271-0). Zhi-Xiang Yu of Peking University described an alternative approach to 5 (Org. Lett. 2017, 19, 6040, DOI: 10.1021/acs.orglett.7b02656; Org. Lett. 2022, 24, 5902, DOI: 10.1021/acs.orglett.2c02111).

The gibberellins, represented by gibberellin A18 (8), regulate a variety of plant development processes. Mingji Dai of Emory University developed a concise route to 8 from commercial andrographolide, a key step of which was the SmI2-mediated conversion of the cyclobutane 6 to the tertiary alcohol 7 (J. Am. Chem. Soc. 2023, 145, 53. DOI: 10.1021/jacs.2c12470).

Isoneoamphilectane (11), isolated from the tropical marine sponge Cymbastela hooperi, shows activity against Mycobacterium tuberculosis H37Rv. Christopher D. Vanderwal of the University of California Irvine assembled the unusual tricyclic skeleton of 11 by the cyclization of 9 to 10 (J. Am. Chem. Soc. 2023, 145, 3716. DOI: 10.1021/jacs.2c13137).

The stelletins, represented by stelletin E (14), isolated from sponges of the genus Stelleta, show remarkable selective cytotoxicity. Xiaozhen Jiao and Ping Xie of the Institute of Materia Medica established a practical route to an advanced intermediate in the synthesis of 14, centered on the intramolecular dipolar cyclization to 13 of the nitrile oxide derived from the aldehyde 12 (Org. Biomol. Chem. 2023, 21, 3850. DOI: 10.1039/D3OB00319A).

Puberuline C (17) was isolated from a traditional Chinese medical plant, Aconitum barbatum var. puberulum. Masayuki Inoue of the University of Tokyo assembled the ketone 16, having the pentacylic core of 17, by the cascade radical cyclization of 15 (J. Am. Chem. Soc. 2023, 145, 600. DOI: 10.1021/jacs.2c11259).

D. F. Taber, Org. Chem. Highlights 2023, December 25.