The taxane diterpenes comprise a group of plant-derived natural products possessing intriguing and important biological activity. In their interaction with the cytoskeleta and constituent proteins, several of the taxanes are unique among molecules acting on this cellular system and this mode of action further manifests itself in significant anti-leukemic and anti-tumor activity for several members of the group. In particular, taxol is now undergoing clinical trial for possible use as a chemotherapeutic agent against cancer. Low natural abundance of the taxanes, the desire to identify sub-structural elements responsible for their biological activity, the possibility that structurally modified taxanes might prove more advantageous therapeutically, and the organic chemical interest in their complex structures make these substances prime candidates for total synthesis research. The long range goal of the present research is to develop a general and flexible synthesis of the taxanes thereby providing synthetic access to natural substances of proven activity and to their structural analogues. Specifically, the initial objective will be to construct taxinine, a taxane possessing many structural features in common with the more complex and biologically active members. This work will model, in part, the eventual synthesis of taxol, representative of the most chemically and biologically intriguing taxanes. Finally, the preparation of enantiomerically pure taxanes, especially taxol, will be probed.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA041349-03
Application #
3181749
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1986-05-01
Project End
1989-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Bryn Mawr College
Department
Type
Schools of Arts and Sciences
DUNS #
City
Bryn Mawr
State
PA
Country
United States
Zip Code
19010