Monday, January 20, 2025
Douglass F. Taber
University of Delaware
C-O Ring Construction: Boscartin H (Sugita), Hypocretenolide (Ding/Wang/Chen), Oxacyclododecindione (Opatz), Merrillianin (Shiina/Murata), Incargranine A (Dixon), Berkelic Acid (Yoshida)
Boscartin H (3) was isolated from frankinscence, the gum resin of Boswella carterii Birdw, widely used in Chinese traditional medicine. Kazuyuki Sugita of Hoshi University established the second tetrahydrofuran ring of 3 by selective epoxidation of 1 followed by acid-mediated cyclization to 2 (J. Org. Chem. 2024, 89, 8924. DOI: 10.1021/acs.joc.4c00797).
Hypocretenolide (6) was isolated from the Mediterranean Asteraceae Hypochoeris cretensis. Yahui Ding, Liang Wang and Yue Chen of Nankai University established the bridged ether of 7 by the addition of 5 to the carvone-derived enone 4 followed by cyclization (Chem. Sci. 2024, 15, 6397. DOI: 10.1039/D4SC01469C). The authors showed that 7 so prepared was almost as effective as 5-fluorouracil in extending the lifetime of mice bearing metastatic colon cancer.
Oxacyclododecindione (10), isolated from the imperfect fungus Exserohilum rostratum, showed potential as a lead structure for the development of antiinflammatories. Till Opatz of Johannes Gutenberg-University constructed the macrolide ring of 10 by the intramolecular Friedel-Crafts cyclization of the t-butyl ester 8 to 9. The tertiary alcohol of 10 was then installed by oxidative decarboxylation (J. Org. Chem. 2024, 89, 5746. DOI: 10.1021/acs.joc.4c00333).
Merrillianin (13) was isolated from the Southeast Asian tree Illicium merrillianum, used in medicinal chemistry since ancient times. Isamu Shiina and Takatsugu Murata of the Tokyo University of Science assembled 13 by way of the intramolecular Michael cyclization of the acetate 11 to the lactone 12 (Org. Lett. 2024, 26, 3327. DOI: 10.1021/acs.orglett.3c03877).
Incargranine A (16) was isolated from the Chinese trumpet-creeper Incarvillea mairei var. grandiflora. In another intramolecular Michael reaction, Darren J. Dixon of the University of Oxford developed a bifunctional iminophosphorane catalyst that cyclized the prochiral cyclohexadienone 14 to the lactone 15 in high ee and as a single diastereomer. Selective decarboxylation followed by reduction and intramolecular Mannich ring closure then completed the synthesis of 16 (Angew. Chem. Int. Ed. 2024, 63, e202314308. DOI: 10.1002/anie.202314308).
Berkelic acid (19) was isolated from an extremophile Penicillium fungus found in the Berkeley Pit in Butte, Montana. En route to 19, Masahito Yoshida of the University of Tsukuba cyclized the alkyne 17 directly to the spiroketal 18 (Chem. Commun. 2024, 60, 3331. DOI: 10.1039/D4CC00166D).
D. F. Taber, Org. Chem. Highlights 2025, January 20.
URL: https://www.organic-chemistry.org/Highlights/2025/20January.shtm