Abstract

) The first objective of this proposal is to study a novel methodology that allows access to substituted quinones and evaluate its scope and limitations during the synthesis of bioactive natural products, such as ilimaquinone avarone and avarol. The second objective of this proposal is the synthesis of norrisolide, a natural product for which in vivo studies have demonstrated that it causes irreversible vesiculation of the Golgi complex. A third objective of our research is the synthesis of borrelidin, an unusual macrolide with a very potent profile as an angiogenesis inhibitor.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA086079-02
Application #
6514501
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lees, Robert G
Project Start
2001-03-01
Project End
2006-02-28
Budget Start
2002-03-01
Budget End
2003-02-28
Support Year
2
Fiscal Year
2002
Total Cost
$200,096
Indirect Cost

  Institution

Name
University of California San Diego
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Guizzunti, Gianni; Brady, Thomas P; Malhotra, Vivek et al. (2007) Trifunctional norrisolide probes for the study of Golgi vesiculation. Bioorg Med Chem Lett 17:320-5
Alexander, Matthew D; Burkart, Michael D; Leonard, Michael S et al. (2006) A central strategy for converting natural products into fluorescent probes. Chembiochem 7:409-16
Guizzunti, Gianni; Brady, Thomas P; Malhotra, Vivek et al. (2006) Chemical analysis of norrisolide-induced Golgi vesiculation. J Am Chem Soc 128:4190-1
Brady, Thomas P; Kim, Sun Hee; Wen, Ke et al. (2005) Norrisolide: total synthesis and related studies. Chemistry 11:7175-90
Tisdale, Eric J; Slobodov, Irina; Theodorakis, Emmanuel A (2004) Unified synthesis of caged Garcinia natural products based on a site-selective Claisen/Diels-Alder/Claisen rearrangement. Proc Natl Acad Sci U S A 101:12030-5
Ghosh, Subhash; Rivas, Fatima; Fischer, Derek et al. (2004) Stereoselective synthesis of the ABC ring system of norzoanthamine. Org Lett 6:941-4
Vong, Binh G; Kim, Sun Hee; Abraham, Sunny et al. (2004) Stereoselective total synthesis of (-)-borrelidin. Angew Chem Int Ed Engl 43:3947-51
Brady, Thomas P; Kim, Sun Hee; Wen, Ke et al. (2004) Stereoselective total synthesis of (+)-norrisolide. Angew Chem Int Ed Engl 43:739-42
Brady, Thomas P; Wallace, Erin K; Kim, Sun Hee et al. (2004) Fragmentation of Golgi membranes by norrisolide and designed analogues. Bioorg Med Chem Lett 14:5035-9
Vong, Binh G; Abraham, Sunny; Xiang, Alan X et al. (2003) Synthetic studies on borrelidin: enantioselective synthesis of the C1-C12 fragment. Org Lett 5:1617-20

Showing the most recent 10 out of 15 publications