This proposal describes the continuation of a project that involves the synthesis of biologically active molecules containing, or derived from molecules containing the cyclopentenone ring system. Target molecules currently under investigation, and proposed target molecules for future research include quadrone, laurenene, the pentalenolactones, carbacyclins, and hydrazulenes. These molecules display a wide range of biological activity and include antibiotics, cytotoxics and anti-cancer agents, and therapeutic agents for circulatory disorders. The methodology to be used is derived from the organometallic cycloaddition processes which have been highly successful in the past at permitting synthetic schemes to bypass much conventional synthetic methodology. The current state of the art permits prediction of success with considerable confidence. This proven methodology is proposed to be supplemented with several new concepts that, taken together, are aimed at addressing those situations in which the methodology does not succeed satisfactorily, and at modifying the existing procedures to permit ready access in a practical way to the desired target molecules in optically active form. The overriding goal of the proposed research will be to generate methodology derived from unique new combinations of several technologies, to permit access to molecules of biomedical importance in their most biologically active forms, as efficiently as possible from readily available materials.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM026294-11
Application #
2174682
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1993-09-01
Project End
1996-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
11
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California Davis
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Olmstead, M M; Price, M E; Strutzel, J et al. (1991) Structure of an unusually non-polar hydroxy ether. Acta Crystallogr C 47 ( Pt 3):563-6