The principal objective of the research proposed herein is the development of a new and general synthetic protocol for the preparation of a variety of medicinally important alkaloids and other nitrogen-containing natural products. A unified strategy for the synthesis of a diverse array of these materials would be attractive, as opposed to the more traditional approach involving a different strategy for each target. The target substructure, a pyrrolidine fused to another ring at the 2- and 3-positions, is widespread in nature. To prepare this subunit, the intramolecular cycloaddition of a 2-azaallyl anion onto an olefin is proposed. The flexibility of this method will be demonstrated through the synthesis of biomedically important nitrogen-containing compounds such as dendrobine, scandine, lycorine, and others, including some angiotension converting enzyme inhibitors. A concurrent goal is the investigation of the poorly understood chemistry of 2-azaallyl anions themselves. Model work has shown that the intramolecular cycloadditions of these species are feasible, but much work regarding their generation and the scope, stereochemistry, and regiochemistry of the cycloadditions must be addressed. Within the framework of natural products synthesis, these unexplored areas in the chemistry of these fascinating intermediates will be addressed.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037100-02
Application #
3292097
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1986-07-01
Project End
1989-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Arts and Sciences
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109