Diels-Alder Cycloaddition: Fawcettimine (Yokoshima), Teucvin (Cai), Phleghenrine A (Dai), 1-Deacetylcaesalmin C (Carreira), Pedrolide (Carreira), Orientanoid A (Ai/Fan/Yue)

Satoshi Yokoshima of Nagoya University prepared several Lycopodium alkaloids starting from fawcetimine (4). A key step in the assembly of 4 was the cycloaddition of the cyclohexenone 1 with the diene 2 to give 3 (Org. Biomol. Chem. 2023, 21, 6289. DOI: 10.1039/D3OB01065A).

Quan Cai of Fudan University used teucvin (8) as the starting point for the construction of several additional clerodane diterpenes. They prepared 8 by the cycloaddition of the enol ether 5 with the pyrone 6, leading to the tricyclic lactone 7 (Chem. Sci. 2023, 14, 12598. DOI: 10.1039/D3SC04335E).

Phleghenrine A (12), isolated from Phleghmariuris henryi Ching, is a 4.91 µM inhibitor of acetylcholinesterase, with low inhibition of butylcholinesterase. Mingji Dai of Emory University constructed 12 via oxidation of the phenol 9 to the ketal dienone, followed by addition to the cyclic enamine 10, to give the tricyclic 11 (Org. Lett. 2023, 25, 5258. DOI: 10.1021/acs.orglett.3c01784).

A study of stimulants of respiration rates in brown adipocyctes led Erick M. Carreira of ETH Zurich to the cassane furanoditerpenoid 1-deacetylcaesalmin C (15). They assembled 15 by the internal Diels-Alder cycloaddition of the tethered ketal 13, leading to 14 (J. Am. Chem. Soc. 2023, 145, 21562. DOI: 10.1021/jacs.3c07597).

Isolated from Euphorbia pedroi, pedrolide (19) is a nontoxic diterpenoid with P-glycoprotein inhibitory properties. Professor Carreira showed that exposure of the norbornadiene 16 to the tetrazine 17 liberated the intermediate 5-alkyl cyclopentadiene, that then combined with the unsaturated lactone, leading to 18, having almost the entire carbon skeleton of 19 (J. Am. Chem. Soc. 2023, 145, 8332. DOI: 10.1021/jacs.3c02113).

Jing Ai, Yao-Yue Fan and Jian-Min Yue of the Shanghai Institute of Materia Medica isolated orientanoid A (22) from Hedyosmum orientale Merr. et Chun. Following the likely biosynthesis, they showed that cycloaddition between the α-methylene lactone 20 and the diene 21 led to 22 as the major diastereomer (Chem. Sci. 2023, 14, 13410. DOI: 10.1039/D3SC04238C).