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.
