Diels-Alder Cycloaddition: Ilicicolin H (Tang/Li), Lucidumone (Li), Venenatine (Zu), Chuanxiongolide L1 (Li/Zheng), Verrubenzospirolactone (Dethe), Pedrolide (Li)

Ilicicolin H (3), isolated from the "imperfect fungus" Cylindrocladium iliciola MFC-8708, is a broad-spectrum antifungal agent. In the course of a synthesis of 3, Yu Tang and Dehai Li of the Ocean University of China showed that the single methyl substituent on the three-carbon bridge between the dienes of 1 was sufficient to direct the stereochemical course of the cyclization to 2 (Tetrahedron Lett. 2024, 142, 155095. DOI: 10.1016/j.tetlet.2024.155095).

Lucidumone (6), isolated from the fruiting bodies of the cultivated mushroom Ganoderma lucidum, selectively inhibits COX-2. To prepare the bridged skeleton of 6, Guang Li of the Institute of Materia Medica assembled 4, with a silicon joining the diene and the dienophile, then used a Cu catalyst to cyclize it to 5 (Nature Commun. 2024, 15, 2647. DOI: 10.1038/s41467-024-46896-3).

The yohimbine alkaloid venenatine (10), isolated from Alstonia venenata, a medicinal plant of India, inhibits the analgesic effect of morphine. Liansuo Zu of Tsinghua University showed that the readily-prepared racemic photodimer 8 of 2-pyrone (7), used in excess, could be combined with 4-methoxytryptamine (9) in the presence of a BINOL-derived phosphoric acid to give the Pictet-Spengler product, and thus 10, in 91% ee (Nature Commun. 2024, 15, 941. DOI: 10.1038/s41467-024-45140-2).

Chuanxiongolide L1 (13), isolated from the rhizome of Ligusticum chuanxiong Hort, inhibited lipopolysaccharide-induced nitric oxide production in RAW 24.7 macrophage cells. Pengfei Li and Huaiji Zheng of the Northwest Agriculture & Forest University showed that the enantiomerically-pure hemiacetal of 11 directed the cyclization to 12 with a modest 1.2:1 diastereoselectivity (Org. Lett. 2024, 26, 2928. DOI: 10.1021/acs.orglett.4c00411).

Verrubenzospirolactone 15 was isolated from the soft coral Sinularia verruca. Dattatraya H. Dethe of the Indian Institute of Technology-Kanpur prepared 15 by the room temperature cyclization of the tetraene 14 (Org. Lett. 2024, 26, 3010. DOI: 10.1021/acs.orglett.4c00605).

Pedrolide (19), isolated from Euphorbia pedroi, is a nontoxic diterpenoid with P-glycoprotein inhibitory properties. En route to 19, Chuang-Chuang Li of the Southern University of Science and Technology used a Hayashi-Jørgensen amine to mediate the three-component coupling of the unsaturated aldehyde 16, cyclopentadiene 17 and the phosphorane 18, leading to the ester 19 (J. Am. Chem. Soc. 2024, 146, 2928. DOI: 10.1021/jacs.3c14150).