The proposed research is aimed at devising and executing a total synthesis of the stephacidins, structurally novel alkaloids that exhibit potent in vitro cytotoxic activity against certain testosterone-dependent prostate cell lines. The proposal includes several new strategies aimed at accessing the recurring 6-oxyindole motif in short order from readily available materials. In addition, a new method for the enantioselective construction of the unusual bicyclo[2.2.2]diazaoctane core is presented. Finally, it is hoped that conditions can be found to reliably and efficiently prepare indolyl nitrones (imine N-oxides) from the parent indoles. Ideally, these and other strategies would be used prepare the stephacidins themselves as well as analogs not only for evaluations of bioactivity, but also to elucidate the unknown mechanism by which they operate.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31GM070414-05
Application #
7264617
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Toliver, Adolphus
Project Start
2003-09-15
Project End
2008-07-14
Budget Start
2007-09-15
Budget End
2008-07-14
Support Year
5
Fiscal Year
2007
Total Cost
$26,398
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037