Organic Chemistry Portal
Organic Chemistry Highlights

Monday, April 17, 2017
Douglass F. Taber
University of Delaware

C-O Ring Construction: Vibralactone (Brown), Obtusallene X (Braddock), Polyrhacitide A (Subba Reddy), α-Levantenolide (Waymouth/Dai), Macrocidin A (Schobert), Paecilomycin F (Banwell)

Vibralactone (3) is a potent (presumably covalently-binding) inhibitor of pancreatic lipase. Richard C. D. Brown of the University of Southampton established (Org. Lett. 2016, 18, 5971. DOI: 10.1021/acs.orglett.6b03007) the β-lactone of 3 by cyclizing 1 to 2.

Obtusallene X (7) is one of a family of polyhalogenated macrocyclic ethers isolated from red algae of the genus Laurencia. D. Christopher Braddock of Imperial College London constructed (J. Org. Chem. 2016, 81, 9539. DOI: 10.1021/acs.joc.6b02008) the central halogenated core 6 of 7 by the diastereoselective cyclization of 4 with the brominating agent TBCO (5).

Polyrhacitide A (11) was isolated from the edible Chinese black ant Polyrhacis vicina, advertised for its anti-inflammatory activity. B. V. Subba Reddy of the Centre for Semiochemicals, Hyderabad devised (Org. Biomol. Chem. 2016, 14, 8832. DOI: 10.1039/C6OB01686C) the cascade addition of 9 to 8, leading to 10.

α-Levantenolide (14) was isolated from Turkish tobacco. Robert M. Waymouth of Stanford University and Mingji Dai of Purdue University established (J. Am. Chem. Soc. 2016, 138, 10693. DOI: 10.1021/jacs.6b06573) a route to 14 from commercial (+)-sclareolide (12). Kulinkovich cyclopropanation led to 13 as a mixture of diastereomers. Pd-catalyzed cyclocarbonylation then proceeded with high regioselectivity, to give, after selenylation and oxidation, the butenolide 14.

The tetramic acid macrocidin A (17), isolated from the fungus Phoma macrostoma, shows remarkable species-selective herbicidal activity. Rainer Schobert of the University of Bayreuth demonstrated (Org. Lett. 2016, 18, 6352. DOI: 10.1021/acs.orglett.6b03240) that the macrocyclic ring of 17 could be assembled by intramolecular alkylation of the phenolate derived from 15, leading to 16.

The resorcylic acid lactone paecilomycin F (20), isolated from the filamentous fungus Cochliobolus lunatus, has antimalarial activity. En route to 20, Martin G. Banwell of the Australia National University observed (Org. Lett. 2016, 18, 4226. DOI: 10.1021/acs.orglett.6b01963) that the reductive cyclization of 18 with indium gave 19 with high regioselectivity. It is striking that exposure of 18 to CrCl2/NiCl2 led to the alternative regioisomer.

D. F. Taber, Org. Chem. Highlights 2017, April 17.