Complementary routes fashion anticancer natural product

For the first time, chemists have made kibdelone C, a polyketide with intriguing anticancer activity from a rare Australian soil microbe. The work was carried out by two teams that shared some information and arranged for their chemistry to be published back-to-back (J. Am. Chem. Soc., DOI: 10.1021/ja203642n and 10.1021/ja204040k). Both Joseph M. Ready of the University of Texas Southwestern Medical Center and John A. Porco Jr. of Boston University were drawn to kibdelone C’s densely functionalized six-ring structure, as well as to the possibility that it might kill cancer cells in a new way. But they tackled the molecule differently. Ready’s team made use of a Shi epoxidation and a palladium-mediated intramolecular C–H arylation, while Porco’s group opted for a platinum-catalyzed intermolecular arylation and a tandem oxa-Michael reaction/Friedel-Crafts cyclization. Ready says he learned about Porco’s work when Porco published a preliminary effort, and Ready shared his own team’s strategy when Porco visited UT Southwestern. “Joe’s group and my group were sharing a lot of information toward the end, especially with respect to purification,” because kibdelone C is unstable, Porco says.