The cembrane diterpenes are a large class of 14-membered-ring-containing natural products, many of which show potentially valuable biologically activity. For example, many representative members of the class (lobohedleolide, crassin acetate, asperdiol, 13,14-bis-epijeunicin, sinularin, dihydrosinularin, and sarcophytol B) show considerable anticancer activity both in vitro and in vivo. In spite of this biological activity, relatively little synthetic work has been carried out in the field, probably because few methods exists for preparing large-ring carbocycles. We have devised new synthetic methods for preparing large-ring cycloalkenes, large-ring 1,2-diols, and large-ring ketones. These methods, which involve treatment of a diketone (aldehyde) or keto ester with titanium metal, appear uniquely suited for cembranoid synthesis. We therefore propose to use our methods for the synthesis of several naturally occurring cembranoids of increasing complexity - sarcophytols A and B, cembranolide, lobophytolide, and sinularin. By so doing, we hope to make these natural products and their analogs more readily available for study and testing. In addition, we hope to extend our knowledge of reaction selectivity in these large-ring compounds.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA037005-02
Application #
3174683
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1984-03-01
Project End
1987-02-28
Budget Start
1985-03-01
Budget End
1986-02-28
Support Year
2
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850