Cyclopentanoid natural products display a wide variety of biological activities, and exhibit diverse and complicated architectures. Total synthesis provides the most efficient vehicle for the examination of these molecules' biological effects. Access to natural products and natural product-like compounds also offers a powerful tool for the elucidation and study of the affected biochemical pathways. Chloriolins B and C are highly oxygenated, chlorinated, linearly fused triquinane natural products recently isolated from an unidentified fungus taken from the Indo-Pacific sponge Jaspis aff. johnstoni. This proposal describes the enantioselective total synthesis of these novel molecules. The proposed synthesis involves the development of the asymmetric trimethylenemethane cycloaddition with activated olefins, and its use in establishing the cis-fused BC ring system. A proposed diastereoselective [3+2] cycloaddition will construct the A ring, and will set the stereochemistry at the AB ring fusion. Successful completion of the total synthesis will constitute the first total synthesis of Chloriolins B and C. This project will also introduce a new method for the asymmetric enantioselective synthesis of five-membered rings and demonstrate its usefulness in complex molecule synthesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM064187-01
Application #
6405094
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Marino, Pamela
Project Start
2001-09-30
Project End
Budget Start
2001-09-30
Budget End
2002-09-29
Support Year
1
Fiscal Year
2001
Total Cost
$33,260
Indirect Cost
Name
Yale University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520