Total syntheses of the pyrrole-imidazole alkaloids dibromophakellstatin and dibromophakellin

ORGN 443

Amanda P. Skoumbourdis, skoumbourdisa@niddk.nih.gov, The Chemical Biology Core Facility, The National Institutes of Health: NIDDK, 9000 Rockvillle Pike, Blgd. 8, Rm. 117, Bethesda, MD 20892 and Ken S. Feldman, ksf@chem.psu.edu, Department of Chemistry, Pennsylvania State University, 104 Chemistry Building, University Park, PA 16802.
A Pummerer-like process was used to form the key tetracyclic core of dibromophakellstatin and dibromophakellin, small but highly functionalized molecules. The 2-thiophenyl imidazole fragment was built utilizing well-precedented metalation chemistry, with further manipulation furnishing the key intermediate, an imidazole-pyrrole species. The oxidative cyclization was induced by treatment with Stang's reagent (PhICNOTf). The tetracyclic product, isolated in fair yield, was readily hydrolyzed to (±)-dibromophakellstatin. A two-step procedure, utilizing a pseudourea intermediate formed from dibromophakellstatin, furnished (±)-dibromophakellin.

 

Total Synthesis of Complex Molecules
8:00 AM-12:00 PM, Wednesday, 29 March 2006 Georgia World Congress Center -- C301, Oral

Division of Organic Chemistry

The 231st ACS National Meeting, Atlanta, GA, March 26-30, 2006