Organic Chemistry Portal
Organic Chemistry Highlights

Monday, August 19, 2019
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Mitrephorone A (Carreira), Pericoannosin A (Kalesse), Dendrobine (Plietker), Aspochalasin B (Liu/Tang; Deng; Trauner), Septedine (Li), Cossonidine (Kisunzu/Sarpong)

The oxetane-containing mitrephorone A (3), isolated from the Bornean shrub Mitrephora glabra, shows remarkable antimicrobial and cytotoxicity. Erick M. Carreira of ETH Zürich established the tricyclic core 2 of 3 by the Diels-Alder cyclization of 1 (J. Am. Chem. Soc. 2018, 140, 16704. DOI: 10.1021/jacs.8b09685).

Pericoannosin A (7), produced by the endophytic fungus Periconia sp. F-31, shows moderate anti-HIV activity. En route to 7, Markus Kalesse of the Leibniz Universität Hannover showed that the Evans auxiliary of 4 effectively directed the absolute sense of the cycloaddition with the acyclic diene 5, leading to 6 (Org. Lett. 2018, 20, 4475. DOI: 10.1021/acs.orglett.8b01768).

Dendrobine (11), isolated from the orchid Dendrobium nobile Lindl, is a classic challenge in alkaloid total synthesis. Bernd Plietker of the Universität Stuttgart set the absolute configuration of 11 by the enantioselective Yb-catalyzed addition of 8 to 9, leading to 10 (Org. Lett. 2018, 20, 4328. DOI: 10.1021/acs.orglett.8b01782).

Three research groups essentially simultaneously announced the Diels-Alder cycloaddition of 13 to 12, leading to 14 and thus to aspochalasin D (15). Gang Liu and Yefeng Tang of Tsinghua University promoted the addition with Cu(OTf)2 (Angew. Chem. Int. Ed. 2018, 57, 14216. DOI: 10.1002/anie.201808249). Jun Deng of the Kunming Institute of Botany used thermal cycloaddition (Angew. Chem. Int. Ed. 2018, 57, 14221. DOI: 10.1002/anie.201808481). Dirk Trauner of New York University promoted the cycloaddition with high pressure (Angew. Chem. Int. Ed. 2018, 57, 15587. DOI: 10.1002/anie.201809703).

Septedine (18) was isolated from the toxic flowering perrenial Aconitum septentrionale ("wolfsbane"). Ang Li of the Shanghai Institute of Organic Chemistry reported the remarkable cyclization of 16 to 17. The conversion to 18 featured an elegant display of late-stage functionalization (J. Am. Chem. Soc. 2018, 140, 9025. DOI: 10.1021/jacs.8b03712).

The very similar cyclization of 19 to 20, reported by Jessica K. Kisunzu of Colorado College and Richond Sarpong of the University of California, Berkeley in the course of a synthesis of the alkaloid cossonidine (21), required much more forcing conditions. The authors concluded that the rotation of the vinyl group into position for the cycloaddition was hindered by the pendant methoxy (J. Am. Chem. Soc. 2018, 140, 8105. DOI: 10.1021/jacs.8b05043).

D. F. Taber, Org. Chem. Highlights 2019, August 19.