Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 29, 2022
Douglass F. Taber
University of Delaware

Other Methods for Carbocyclic Construction: Piperarborenine B (Antonchick), Nakafuran-8 (Houk/Li), Cochlearol B (Sugita), Talatisamine (Reisman), Berkeleyone A (Li), Prostratin (Inoue)

Piperarborenine B (3), isolated from the stem of Piper arborescens, shows significant and selective antineoplastic activity. Andrey P. Antonchick of Nottingham Trent University constructed the cyclobutane core of 3 by oxidative nitrogen extrusion from the pyrrolidine 1 to give 2 (J. Am. Chem. Soc. 2021, 143, 18864. DOI: 10.1021/jacs.1c10175).

Nakafuran-8 (6), isolated from the marine sponge Dysidea fragilis and from its prey, the nudibranchs Hypselodoris godeffroyana and Chromodoris maridadilus, is an inhibitor of human tyrosine phosphatase 1B. K. N. Houk of UCLA and Chuang-Chuang Li of the Southern University of Science and Technology established the bicyclic core 5 of 6 by the [3+2] intramolecular dipolar cyclization of the N-sulfonyltriazole 4, followed by hydrolysis and reduction (Nature Commun. 2021, 12, 5239. DOI: 10.1038/s41467-021-25513-7).

Cochlearol B (9) was isolated from the fruiting body of the fungus Ganoderma cochlear, used in traditional Chinese medicine. En route to 9, Kazuyuki Sugita of Hoshi University effected the intramolecular [2+2] photocycloaddition of the cyclohexenone 7 to 8 (Angew. Chem. Int. Ed. 2021, 60, 24484. DOI: 10.1002/anie.202110556).

Talatisamine (12), a delphinine alkaloid extracted from the flowering shrub Aconitum talassicum of Central Asia, is a K+ channel blocker with hypotensive and antiarrhythmic activities. Sarah E. Reisman of Caltech set the stage for the synthesis of 12 by the photocyclization of the phenyl ether 10, followed by epoxidation and rearrangement, to give 11 (ACS Cent. Sci. 2021, 7, 1311. DOI: 10.1021/acscentsci.1c00540).

Berkeleyone A (15), isolated from a strain of the fungus Penicillium rubrum growing in the Berkeley Pit, was found to have potent anti-inflammatory activity. Houhua Li of Peking University constructed the intermediate diketone 14 by Krapcho demethoxycarbonylation of 13 and subsequent cyclization (Angew. Chem. Int. Ed. 2021, 60, 14869. DOI: 10.1002/anie.202104014).

Prostratin (18), isolated from the bark of the mamala tree of Samoa, Homalanthus nutans, strongly activates HIV replication in latently infected cells. In the course of a synthesis of 18, Masayuki Inoue of the University of Tokyo achieved high diastereoselectivity in the free radical cyclization of the cyclopentenone 16 to the tetracyclic 17 (J. Am. Chem. Soc. 2021, 143, 12387. DOI: 10.1021/jacs.1c06450).

D. F. Taber, Org. Chem. Highlights 2022, August 29.