This program is directed toward the total synthesis of the powerful antifeedant agent azadirachtin (1) isolated from the neem tree whose extracts have been used for centuries as antifungal, antiviral, and antimalarial agents. The daunting nature of this challenging synthetic target invites new strategies for the construction of polycyclic systems and crowded carbon-carbon bonds and promises discovery, invention and development of new synthetic technologies. The designed convergent strategies toward azadirachtin (1) are variants of a general concept involving construction of advanced key building blocks representing the decalin and dihydrofuran domains of the molecule followed by tethering and intramolecular formation of the crowded C8-C14 carbon-carbon bond via radical or organometallic species. The proposed work is expected to impact the general areas of pharmaceutical and agricultural research, and infectious diseases in particular, through discoveries in synthetic organic chemistry and chemical biology.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI051440-05
Application #
7332247
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Tseng, Christopher K
Project Start
2004-01-01
Project End
2008-12-31
Budget Start
2008-01-01
Budget End
2008-12-31
Support Year
5
Fiscal Year
2008
Total Cost
$436,479
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037