Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 30, 2021
Douglass F. Taber
University of Delaware

Other Methods for Carbocyclic Construction: COTC (Buda), Brussonol (Jin/Qiu), Lingzhiol (Luo/Qin), Melicolone A (Martin), Macfarlandin C (Overman), Mitrephorone A (Carreira)

The crotonate ester COTC (3), an inhibitor of alkaline phosphodiesterase isolated from a soil Streptomyces, had cytotoxic and cancerostatic activity. Szymon Buda of Jagiellonian University prepared the carbocyclic core 2 of 3 by cyclizing the ribose-derived aldehyde 1 with selenide (Tetrahedron 2020, 76, 131397. DOI: 10.1016/j.tet.2020.131397).

The icetexane diterpene brussonol (7), isolated from Russian sage, Perovskia atriplicifolia, is moderately cytotoxic toward P388 murine leukemia cells. Yehua Jin of Launch Pharma Technologies and Fayang G. Qiu the Guangzhou Institutes of Biomedicine and Health assembled the tetracyclic skeleton 6 by the addition of the oxidopyrylium derived from 4 to the diene 5 (Org. Lett. 2020, 22, 7415. DOI: 10.1021/acs.orglett.0c02309).

Lingzhiol (10), isolated from the medicinal reishi fungus Ganoderma lingzhi, ameliorated adriamycin-induced nephropathy in mice. Sanzhong Luo of Tsinghua University and Hong-Bo Qin of the Kungmin Institute of Botany constructed the carbon skeleton of 10 by the diastereoselective cyclization of 8 to 9 (Chem. Commun. 2020, 56, 10066. DOI: 10.1039/D0CC04064A).

Melicolone A (14), isolated from the leaves of the dioecious medicinal shrub Melicope ptelefolia of Southeast Asia, showed a protective activity against high glucose-induced oxidative stress in human vein endothelial cells. En route to 14, Stephen F. Martin of the University of Texas showed that the carbonyl ylide derived from 11 added to the dienone 12 to give 13 with high regio- and diastereoselectivity (Org. Lett. 2020, 22, 9071. DOI: 10.1021/acs.orglett.0c03454).

Macfarlandin C (17), isolated from the dorid nudibranch Chromodoris macfarlandi, induced irreversible fragmentation of the Golgi apparatus. Larry E. Overman of the University of California, Irvine established the octalin core 16 by the acid-catalyzed cyclization of 15, prepared in high ee (J. Org. Chem. 2020, 85, 15532. DOI: 10.1021/acs.joc.0c02273).

The total synthesis of mitrephorone A (21) has previously been addressed in these Highlights (Diels-Alder Cycloaddition: Mitrephorone A (Carreira), Pericoannosin A (Kalesse), Dendrobine (Plietker), Aspochalasin B (Liu/Tang; Deng; Trauner), Septedine (Li), Cossonidine (Kisunzu/Sarpong) 2019, August 19; Diels-Alder Cycloaddition: Pericoannosin A (Lindsley), Arborone (Corey), Furoerioaustralasine (George), Liangshanin G (Ma), Arcutinidine (Sarpong), Mitrephorone A (Magauer) 2020, August 24). Erick M. Carreira of ETH Zürich established an improved approach, based on the diastereoselective dipolar cycloaddition of the nitrile oxide derived from 18, to give 19 (J. Am. Chem. Soc. 2020, 142, 17802. DOI: 10.1021/jacs.0c09520).

D. F. Taber, Org. Chem. Highlights 2021, August 30.