This project concerns the development of an efficient synthesis of CP-263,114, a structurally novel protein farnesyl transferase inhibitor of interest for its potential as an anti-cancer agent. The research has been designed not only to provide access to the natural product itself, but also to a series of analogs which could prove valuable for insight into the nature of the interaction between CP-263, 114 and its biological target. Chemically, the approach to be taken involves both the development of new chemistry and the use of powerful reactions in new contexts to achieve the synthesis in an efficient manner. This will lead to delineation of the chemistry of the unusual ring system of CP-263,114, and to understanding of the principles governing the reaction chemistry that we bring to bear on the problem. Such understanding could ultimately find application to other synthetic endeavors.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM059662-01
Application #
2883092
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1999-09-01
Project End
2003-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Chemistry
Type
Other Domestic Higher Education
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Bio, Matthew M; Leighton, James L (2003) An approach to the synthesis of the phomoidrides. J Org Chem 68:1693-700
Bio, M M; Leighton, J L (2000) Stereoconvergent palladium-catalyzed carbonylation of both E and Z isomers of a 2-trifloxy-1,3-butadiene. Org Lett 2:2905-7