The utility of mitomycin C in cancer chemotherapy has been limited by its toxic side effects. One objective of this research is to develop an efficient synthesis of 1,2-aziridino mitosenes by use of the modified Nenitzescu reaction. The presence of the aziridine ring is essential for high anti-tumor activity and this synthetic approach should open the way for synthesis of a new family of modified aziridino mitosenes differing at C-6. Another aspect of this project is the development of new methodology for diastereo- and enantioselective synthesis of amines, amino alcohols, and other multiply functionalized amino compounds by addition of carbon nucleophiles to nitrones. The stereoelectronic factors and the effects of chelating groups on the C- and N-substituents on the stereoselectivity of nitrone additions will be evaluated. New methods for synthesis of Alpha,Beta-aziridino esters and Beta-lactams via nitrone additions are proposed. A stereoselect-synthesis of L-acosamine, the sugar component of 4'-epi-adriamycin, a promising antitumor agent, and of a thienomycin model compound are outlined to demonstrate the utility of these methods. A family of cyclic and acyclic thioimidate and thiocarbamimidate N-oxides, novel nitrones of thio esters and thio carbonates, are to be synthesized. Inter- and intramolecular cycloadditions as well as acylation-rearrangement reactions of these carboxylate nitrones will be carried out.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA020436-10
Application #
3165299
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1980-04-01
Project End
1989-06-30
Budget Start
1986-07-01
Budget End
1987-06-30
Support Year
10
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820