The pyrrolizidine alkaloids are a large family of natural products which have diverse pharmacological properties, ranging from anesthetic to anti-tumor activity. This proposal presents two approaches to the synthesis of these alkaloids. One route relies upon an N-acyliminium ion rearrangement-cyclization process while the other uses an Alpha-acylamino radical cyclization to construct the pyrrolizidine nucleus. Both approaches are designed to permit the synthesis of stereoisomers of the natural products which might display interesting biological properties. The application of Alpha-acylamino radical cyclizations to the synthesis of other biologically active alkaloid families is also discussed. Approaches to the lycorane group Amaryllidaceae alkaloids as well as a short synthesis of the indolizidine alkaloid dendroprimine are presented. The application of N-acyliminium ion cyclizations to the synthesis of the Lythraceae alkaloid lythrancepine-I is also presented. Intermediates in the synthesis of these alkaloids may display central nervous system activity. A stereochemical study of the oxidative phenolic coupling benzyltetrahydro-isoquinolines is also described. This study may shed light on aspects of morphine synthesis and biosynthesis and should provide morphine and aporphine analogs for evaluation as analgesics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM027647-06
Application #
3274854
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1980-04-01
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Arts and Sciences
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210