Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 21, 2023
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Rameswaralide (Romo), Lucidumone (de la Torre), Anthracimycin (Qian/Tong), Alstonlarsine A (Ferjancic/Bihelovic), Ophiorrine A (Vincent), Daphgraciline (Sun/Li)

Rameswaralide (4), isolated from the soft coral Sinularia dissecta, showed modest cytotoxicity. In the course of a synthesis of 4, Daniel Romo of Baylor University showed that with an enantiomerically-pure benzotetramisole catalyst, acryloyl chloride 2 reacted with only one enantiomer of the diene 1, leading to 3 in high ee (J. Am. Chem. Soc. 2022, 144, 18575. DOI: 10.1021/jacs.2c08245).

Lucidumone (7), isolated from the mushroom Ganoderma lucidum, selectively inhibits COX-2. Aurélien de la Torre of the Université Paris-Saclay constructed the 6, simply converted to 7, by the retro-Diels-Alder/Diels-Alder cyclization of the lactone 5 (J. Am. Chem. Soc. 2022, 144, 17803. DOI: 10.1021/jacs.2c08760).

Anthracimycin (10), isolated from a marine Streptomyces species (CNH365), showed potent activity against Gram-positive bacteria, including MRSA and anthrax. Pei-Yuan Qian and Rongbiao Tong of the Hong Kong University of Science and Technology devised a concise route to 10, based on the cyclization of the triene 8 to the tricyclic lactone 9 (Chem. Sci. 2022, 13, 12776. DOI: 10.1039/D2SC05049H).

Alstonlarsine A (13), isolated from Alstonia scholaris, the "scholar tree" of Southeast Asia, was found to be an inhibitor of DAP kinase-related apoptosis-inducing protein kinase 2 (Drak2), a signaling molecule involved in the regulation of inappropriate T cell activation. Zorana Ferjancic and Filip Bihelovic of the University of Belgrade combined the secondary amine 11 with acetaldehyde, leading to an enamine that cyclized to 12. Selective reduction of the acetate followed by oxidation led to 13 (Angew. Chem. Int. Ed. 2022, 61, e202210297. DOI: 10.1002/anie.202210297).

Ophiorrine A (16) was isolated from the Chinese medicinal plant Ophiorrhiza japonica. Following the likely biosynthesis, Guillaume Vincent, also of the Université Paris-Saclay, assembled 16 by the cyclodehydration of the amide 14, followed by in situ cyclization to 15 (Angew. Chem. Int. Ed. 2022, 61, e202209135. DOI: 10.1002/anie.202209135).

The yuzurine alkaloid daphgraciline (19) was isolated from the evergreen Daphniphyllum gracile Gage of New Guinea. Jianwei Sun, also of the Hong Kong University of Science and Technology, and Chuang-Chuang Li of the Southern University of Science and Technology constructed the tetracyclic core 18 of 19 by the cyclization of the triene 17 (J. Am. Chem. Soc. 2022, 144, 18823. DOI: 10.1021/jacs.2c09548).

D. F. Taber, Org. Chem. Highlights 2023, August 21.