Total synthesis of 34-hydroxyasimicin and its photoactive derivative for affinity labeling of the mitochondrial complex

ORGN 434

Hongna Han1, Mantosh K. Sinha2, Lawrence D'Souza1, Ehud Keinan2, and Subhash C. Sinha1. (1) The Scripps Research Institute, Department of Molecular Biology and the Skaggs Institute for Chemical Biology, 10550 N. Torrey Pines Road, La Jolla, CA 92037, (2) Department of Organic Chemistry, Technion-Israel Institute of Technology, The Scripps Research Institute, Haifa, 32000, Israel

The asymmetric total synthesis of the 34-hydroxyasimicin and its 3-(4-benzoylpheny)propionate ester was achieved via a convergent synthetic strategy. This ester, which contains eight asymmetric centers, represents the first photoaffinity labeling agent that is derived from an Annonaceous acetogenin. The key transformations in the synthesis includes the Sharpless asymmetric dihydroxylation reaction, Wittig olefination reaction, oxidative cyclization reaction with rhenium(VII) oxide, Williamson etherification reaction, and palladium-catalyzed cross-coupling reaction. Using the target molecule for photoaffinity labeling studies of bovine mitochondrial NADH-ubiquinone oxidoreductase (complex I) may shed light on the structure/function of this intricate enzyme and on the origin of high antitumor activity exhibited by the Annonaceous acetogenins.

Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic 9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster Division of Organic Chemistry The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004