Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 30, 2020
Douglass F. Taber
University of Delaware

Diels-Alder Cycloaddition: Prostaglandin E2 (Kagan), Pseudopterosin (-)-G-J aglycone (Vanderwal), Lyconadin D (Yang), Spruceanol (Xue), Scabrolide A (Stoltz)

The sulfoxide 2 and its enantiomer are now both commercially available. In 1992, Henri B. Kagan of the Université Paris-Sud reported that although 2 itself is a sluggish dienophile, activation with the Meerwein reagent led to an intermediate that added to the diene 1 with high diastereoselectivity. Hydrolysis with NaOH led to 3, with inversion of absolute configuration at sulfur, that was carried on to the Corey lactone and thus to prostaglandin E2 (4) (Tetrahedron Asymmetry 1992, 3, 115. DOI: 10.1016/S0957-4166(00)82318-6). Remarkably, this has not been used since. In this application, 2 served as a ketene equivalent. Earlier, Leo A. Paquette of Ohio State University had shown that 2 could also serve as an acetylene equivalent (J. Am. Chem. Soc. 1978, 100, 1597. DOI: 10.1021/ja00473a044).

The pseudopterosins, exemplified by pseudopterosin (-)-G-J aglycone (8), show a range of biological activities. Christopher D. Vanderwal of the University of California, Irvine developed a general route to the pseudopterosins, based on the addition of 6 to the pulegone-derived dienophile 5 (Org. Lett. 2020, 22, 2883. DOI: 10.1021/acs.orglett.0c00486).

Lyconadin D (12) and its des-methyl analogue lyconadin E were isolated from the club moss Lycopodium complanatum (ground pine). Yang Yang of the Huazhong University of Science and Technology devised a synthesis of 12 based on the Diels-Alder addition of 9 to 10 to give 11 (Angew. Chem. Int. Ed. 2020, 59, 2860. DOI: 10.1002/anie.201912948).

In the course of a synthesis of spruceanol (16), Xiaowen Xue of the China Pharmaceutical University prepared the furan 13 from andrographolide. The Diels-Alder cyclization with 14 proceeded with high regioselectivity to give 15, presumably via complexation of the AlCl3 with the diol and with the ester (J. Org. Chem. 2020, 85, 6709. DOI: 10.1021/acs.joc.0c00713).

Scabrolide A (19), isolated from the soft coral Sinularia scabra, inhibits both IL-6 and IL-12. Brian M. Stoltz of Caltech assembled 18 by the diastereoselective cyclization of the ester 17 (J. Am. Chem. Soc. 2020, 142, 8585. DOI: 10.1021/jacs.0c02513).

D. F. Taber, Org. Chem. Highlights 2020, November 30.