Development of Selective Catalytic Reactions by Simulation of the Function of Hepatic Flavoenzyme

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We have been studied simulation of the function of hepatic flavoenzyme with simple organic molecules or simple transition metal complex catalysts. In this project, we studied two types of reactions. 1) Biomimetic asymmetric oxidation reaction catalyzed by simple planar-chiral flavinophanes. 2) Introduction of substituents at alpha to the nitrogen atom of amines via nitrones and application of these methodologies to the synthesis of nitrogen-containing biologically active compounds.1. Planar-chiral flavin catalysts are prepared by capping one of the planes of isoalloxane with a carbon chain. The chiral flavin-catalyzed oxidation of sulfides with hydrogen peroxide gives the corresponding optically active sulfoxides in up to 70% ee. Using the same catalytic system, kinetic resolution of alpha-substituted hydroxylamines by enantiospecific oxidation and asymmetric Baeyer-Villiger oxidation of ketones can be performed.2. Nucleophilic addition of ketene silyl acetals to nitrones can be performed using Lewis acid catalysts such as titanium, boron, and zinc complexes, affording beta-amino acid derivatives with high efficiency. Lewis acid-catalyzed diastereoselective reaction of nitrones with the optically active ketene silyl acetals gives optically active N-hydroxy-beta-amino acid esters in up to 99% de. Chiral Lewis acids catalyze the enantioselective addition of ketene silyl acetals to nitrones to give N-hydroxy-beta-amino acid esters in up to 85% ee.3. Using new methodologies for stereoselective introduction of substituents at alpha to the nitrogen atom of amines via nitrones, nitrogen-containing biologically active compounds such as beta-lactam antibiotics and indolizidine, pyrrolizidine, and necine alkaloids, are synthesized.