Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 23, 2021
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: 4β-Acetoxyprobotryane-9β,15α-diol (Li), Penostatin C (Tong), Sucutinirane C (Pitsinos), Glaucocalyxin A (Jia), PF-1018 (Trauner), Abyssomycin C (Vidali)

4β-Acetoxyprobotryane-9β,15α-diol (3) was isolated from the wine grape necrotrophic fungus Botrytis cinerea. En route to 3, Chuang-Chuang Li of the Southern University of Science and Technology optimized the Rh-catalyzed cycloaddition of 1 to 2 (J. Am. Chem. Soc. 2020, 142, 19868, DOI: 10.1021/jacs.0c10116; Org. Lett. 2016, 18, 4932, DOI: 10.1021/acs.orglett.6b02414).

Penostatin C (6), isolated from the entomogenous fungus Isaria tenuipes, is a 0.37 µM inhibitor of protein tyrosine phosphatase 1B. Rongbiao Tong of the Hong Kong University of Science and Technology assembled the central core 5 of 6 by the intramolecular Diels-Alder cyclization of 4 followed by spontaneous decarboxylation (Org. Lett. 2020, 22, 5074. DOI: 10.1021/acs.orglett.0c01649).

Sucutinirane C (10) was isolated from the South American medicinal plant Bowdichia nitada. Related compounds have shown selective cytotoxicity against cancer cells with increased Hedgehog (Hh) signaling levels. Emmanuel N. Pitsinos of the National Center of Scientific Research "Demokritos" observed high diastereo- and regioselectivity in the Diels-Alder addition of the quinone 8 to the diene 7, leading to 9 (Eur. J. Org. Chem. 2020, 4730. DOI: 10.1002/ejoc.202000724).

Glaucocalyxin A (13), isolated from the Japanese mint Rabdosia umbrosa, ameliorates myocardial ischemia reperfusion injury. Yanxing Jia of Peking University assembled 12, having all the skeletal stereogenic centers of 13, by the unactivated intramolecular Diels-Alder cyclization of 11 (Angew. Chem. Int. Ed. 2020, 59, 15195. DOI: 10.1002/anie.202005932).

PF-1018 (16) was isolated from a fungal strain identified as Humicola sp. 1018 using a screen against the diamond back moth Plutella xylostella. Dirk Trauner of NYU prepared 16 via the designed 8π electrocyclization of 14, followed by in situ Diels-Alder cycloaddition to 15 (Angew. Chem. Int. Ed. 2020, 59, 5263. DOI: 10.1002/anie.201912452).

Sorensen was the first to develop the intramolecular Diels-Alder approach to abyssomycin C (19). Veroniki P. Vidali, also of NCSR "Demokritos", significantly improved on this approach, effecting the oxidation and in situ cyclization of 17 to 18 (Eur. J. Org. Chem. 2020, 4547. DOI: 10.1002/ejoc.202000671).

D. F. Taber, Org. Chem. Highlights 2021, August 23.