Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 16, 2009
Douglass F. Taber
University of Delaware

Complex Cyclic Ethers: (+)-Conocarpan (Hashimoto), (-)-Brevisamide (Satake/Tachibana), (+)-Bruguierol A (Fañanás/Rodríguez), (-)-Berkelic Acid (Snider), and (-)-Aigialomycin D (Harvey)

(+)-Conocarpan (3), isolated from the wood of Conocarpus erectus, exhibits insecticidal, antifungal and antitrypanosomal activity. Shunichi Hashimoto of Hokkaido University developed (J. Org. Chem. 2009, 74, 4418. DOI: 10.1021/jo900502d) a chiral Rh (II) carboxylate that effected the cyclization of 1 to 2, setting the absolute configuration of 3.

The dinoflagellate Karenia brevis produces the brevetoxins, a family of complex polyethers. Recently, the first N-containing cyclic ether, (-)-Brevisamide (6), was isolated from K. brevis. Masayuki Satake and Kazuo Tachibana of the University of Tokyo, in their synthesis of 6 (Org. Lett. 2009, 11, 217. DOI: 10.1021/ol802426v) found it convenient to set the relative configuration around the six-membered ring by double hydroboration/oxidation of the diene 4.

(+)-Bruguierol A (9), isolated from the mangrove Bruguiera gymmorrhiza, has an unusual bridged structure. Francisco J. Fañanás and Félix Rodríguez of the Universidad de Oviedo conceived (J. Org. Chem. 2009, 74, 932. DOI: 10.1021/jo8021204) an elegant approach to the construction of 9, based on the Pt-mediated addition of the alcohol of 7 to the alkyne to give a transient enol ether. It is not clear whether the subsequent intramolecular electrophilic addition to the aromatic ring is mediated by the Pt, or by a trace of adventitious acid. The overall transformation was remarkably efficient.

The Berkeley Pit in Butte, Montana, is an abandoned open-pit copper mine filled with 30 billion gallons of pH = 2.5 water heavily contaminated with, inter alia, copper, cadmium, arsenic and zinc. Remarkably, microorganisms can be cultured from that water. (-)-Berkelic Acid (13), isolated from a Penicillium fungus, showed selective activity against OVCAR-3 ovarian cancer. Barry B. Snider of Brandeis University set (Angew. Chem. Int. Ed. 2009, 48, 1283. DOI: 10.1002/anie.200805488) the absolute configuration of the central five-membered ring ether of 13 by conjugate addition of the enantiomerically-pure reagent 11 to the prochiral lactone 10.

(-)-Aigialomycin D (17), isolated from the mangrove fungus Aigialus parvus, was found to be a selective inhibitor of the kinases CDK1, CDK5 and GSK3. The synthesis of 17 reported (J. Org. Chem. 2009, 74, 2271. DOI: 10.1021/jo802561s) by Joanne Harvey of Victoria University of Wellington illustrated the power of the Ramberg-Bäcklund reaction for the closure of medium rings. Three-component coupling allowed the facile assembly of the sulfone 14. Ring-closing metathesis gave 15, that on oxidative SO2 extrusion followed by deprotection gave (-)-Aigialomycin D (17).

D. F. Taber, Org. Chem. Highlights 2009, November 16.