The objectives of this proposal are to continue the development of transition metal-catalyzed [2+2+2]cycloadditions of unsaturated moieties to generate polycyclic frameworks with potential physiological activity.
The specific aims are to use highly reactive forms of cyclopentadienylcobalt to effect low temperature cyclizations of alkynes and nitriles to give specifically substituted arenes and heteroarenes, including aromatic steroids and ergot alkaloids. The cyclization of specifically constructed enediynes should open up ready access to the natural product illudol and the provitamin D nucleus. The recent discovery that the aromatic double bond of indole, pyrrole, imidazole, and furan can be incorporated into this cycloaddition methodology will be exploited in synthetic approaches to lycorane, the aspidosperma alkaloids, the ergot alkaloids, thebaine, strychnine, and other polyheterocycles. The discovery that Alpha,Omega-diynes can be cocyclized with alkenes should provide a general synthetic solution to the problem of linear annelation, a strategy that will be applied to the anthracycline aglycons. Exploratory work will be initiated aimed at incorporating new unsaturated units into this methodology, including C-N, C-O, and allene double bonds. Finally, recently developed syntheses of chiral and optically active cyclopentadienyl ligands should enable their application in transition metal-catalyzed enantioselective transformations, in particular C-C bond formations and hydrogenations.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM022479-14
Application #
3271161
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1979-04-01
Project End
1992-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
14
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704