Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 22, 2022
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Pepluanol A (Gaich), Trichoderone A (Nay), Davasinol (Ding), Nahuoic Acid A (Alvarez/de Lera), Chloropestolide B (Suzuki), Catharanthine (Dixon)

Pepluanol A (3) was isolated from the European milkweed Euphorbia peplus. Tanja Gaich of the University of Konstanz devised a route to 3 based on the intramolecular Diels-Alder cycloaddition of the cis diene 1, leading to the tetracylic 2 (J. Am. Chem. Soc. 2021, 143, 11934. DOI: 10.1021/jacs.1c05257).

Bastien Nay of the Ecole Polytechnique devised the cyclization of the tetraene 4 to the lactam 5 (Org. Lett. 2021, 23, 5755. DOI: 10.1021/acs.orglett.1c01922). The tricycle 5 had already been oxidized to trichoderone A (6) by Pema-Tenzin Puno and Jun Deng of the Kunming Institute of Botany (Angew. Chem. Int. Ed. 2021, 60, 15963. DOI: 10.1002/anie.202102831).

The hetesine-type alkaloid davasinol (9) was isolated from Delphinium davisii Munz of Turkey. En route to 9, Hanfeng Ding of Zhejiang University oxidized the aromatic ring of 7 to a cyclohexadienone that cyclized to the diketone 8 (J. Am. Chem. Soc. 2021, 143, 10576. DOI: 10.1021/jacs.1c05703).

Nahuoic acid A (12) was isolated via a chemical genetics approach from a Streptomyces sp. derived from a marine sediment. The bicyclic 12 is the first reported cofactor-competitive inibitor of the epigenetic enzyme SETD8. Rosana Alvarez and Angel R. de Lera of the Universidade de Vigo synthesized 12 by way of the internal Diels-Alder cyclization of the pentaene 10 to the aldehyde 11 (Chem. Sci. 2021, 12, 15157. DOI: 10.1039/D1SC04524E).

Chloropestolide C (15) was isolated from a scale-up fermentation of Pestalotiopsis fici. Following a biomimetic proposal, Takahiro Suzuki of Hokkaido University showed that under high pressure, the conjugated alkene of 14 added to the diene 13, leading to 15 (J. Org. Chem. 2021, 86, 15597. DOI: 10.1021/acs.joc.1c02108).

Darren J. Dixon of the University of Oxford developed a strategy for the reduction of a dihydropyridone 16 to the dihydropyridine 17 - the long-sought biosynthetic intermediate dehydrosecodine. The isolated product from the reaction was the Vinca alkaloid catharanthine (J. Am. Chem. Soc. 2021, 143, 10828. DOI: 10.1021/jacs.1c04980).

D. F. Taber, Org. Chem. Highlights 2022, August 22.