Two structurally unique compounds, CP-263,114 and CP-225,917, were recently isolated from an unidentified fungus while screening for squalene synthase inhibitors. These natural products were found to inhibit ras farnesyl transferase. One objective of this grant application is to develop a practical and efficient total synthesis of CP-263,114 and CP-225,917 which will allow the production of modified versions of these inhibitors for evaluation against ras farnesyl transferase and squalene synthase.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA075471-01A2
Application #
2759527
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lees, Robert G
Project Start
1999-01-01
Project End
2001-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
047006379
City
College Station
State
TX
Country
United States
Zip Code
77845
Sulikowski, Gary A; Agnelli, Fabio; Spencer, Paul et al. (2002) Studies on the biosynthesis of phomoidride B (CP-263,114): evidence for a decarboxylative homodimerization pathway. Org Lett 4:1447-50
Sulikowski, Gary A; Liu, Weidong; Agnelli, Fabio et al. (2002) Progress toward a biomimetic synthesis of phomoidride B. Org Lett 4:1451-4
Spencer, P; Agnelli, F; Sulikowski, G A (2001) Investigations into the production and interconversion of phomoidrides A-D. Org Lett 3:1443-5
Sulikowski, G A; Agnelli, F; Corbett, R M (2000) Investigations into a biomimetic approach toward CP-225,917 and CP-263,114. J Org Chem 65:337-42