Studies on synthetic applications of stereoselective and regioselective ring opening reactions of aziridinium ions

Aziridinium ions are important reactive intermediates in organic synthesis. Regioselective and stereoselective ring opening reactions of aziridinium ions provide various useful building blocks for synthesis of vincinal amines, amino alcohols and amino esters. Aziridinium ions are also involved in the biological process of anti-cancer agents. However, the aziridinium ions are under-utilized in the organic synthesis. In this thesis, we utilize stereoselective and regioselective ring opening reactions of aziridinium ions for synthesis of enantiomerically enriched compounds.;Ring opening reactions of aziridinium ions was utilized in the intramolecular Friedel-Crafts (FC) reactions for synthesis of 4-substituted tetrahydroquinoline. A series of beta-haloamine was prepared as the precursors of the aziridinium ions. The reaction conditions for the FC reactions were optimized. Further, the reaction mechanism was studied to prove that the aziridinium ions were formed as the key intermediates.;Intermolecular nucleophilic ring opening reaction of aziridinium ions was studied as a convenient method of carbon-carbon formation. Regioselective and stereoselective nucleophilic substitution reactions of aziridinium ions with indoles, malonic ester, and Grignard reagents were carried out for the respective synthesis of optically active tryptamine, gamma-aminobuyric acid, and alpha-amine derivatives.;The regiospecific ring opening reactions of aziridinium ions were applied for the synthesis of bifunctional ligands which have a potential use in targeted therapy and imaging of cancers. The novel bifunctional chelates with a shorter alkyl spacer C-NETA and 2E-C-NETA as well as the chelates with a longer spacer 5p-C-NETA were prepared. The peptide c(RGDyK) was used as a targeting moiety which was conjugated to the 5pC-NETA to accomplish the targeted radiation therapeutic drug. Fluorescent dye Cy5.5 was used as an imaging moiety which was conjugated to the 2E-C-NETA to visualize the cellular uptake of the drug. The results indicated that the bifunctional ligands have promising applications in the biomedical field.;In summary, the stereoselective and regioselective ring opening reactions of aziridinium ions have been successfully applied in the synthesis of optically active compounds such as tetrahydroisoquinolines, tryptamines, gamma-aminobuyric acids, alpha-amine derivatives and bifunctional chelators. By utilizing aziridinium ions as key reactive intermediates, it is simple and convenient to access versatile optically active and synthetic valuable compounds.