Studies On Asymmetric Catalysis And Biological Activity Of Cinchona Alkaloids

Three projects were investigated in my dissertation. The first part was about asymmetric phase-transfer catalysis, the second part was on organocatalytic asymmetric reactions based on iminium activation, and the third part was about synthesis and biological activity of antimicrobial agents.Enantioselective organocatalysis has become a field of central importance for the asymmetric synthesis of chiral molecles. Novel modes of substrate activation have been achieved using organic catalysts that can now deliver unique, orthogonal, or complementary selectivities comparable to many established metal-catalyzed transformations. Notably, the concepts of PTC catalysis and iminium catalysis, both of the youngest subfields of organocatalysis, have grown almost hand in hand with the general field of organocatalysis.In the current work, Polyethylene Glycol (PEG) was a potential carrier used in polymer supported asymmetric catalytic synthesis with perfect water solubility. After chemical modification, it was used as the carrier in the synthesis of three readily available, soluble and recycled polymer-supported cinchona alkaloids. ER, ¹H NMR, ¹³C NMR, and elemental analysis were used for characterization of these catalysts. Moderate to good yields (55-93%) and enantioselectivities (19-86% ee) were obtained in the expoxidation of a range ofα,β-unsaturated enones.Next, to investigate the electronic influence on enantioselectivities of asymmetric phase-transfer reactions, we have designed and synthesized 14 new chiral quaternary ammonium salts from cinchona alkaloids and phenacyl bromide derivatives. These chiral phase transfer catalysts were tested in enantioselctive alkylation of the N-(diphenylmethylene) glycine tert-butyl ester. Different solvents, nucleophiles and catalysts were investigated in this reaction. Under optimal condition, good chemical yields (up to 94%) and excellent enantioselectivities (up to >99% ee).During our continuous studies on the organocatalysis based on iminium strategy, we are interested in the undeveloped asymmetric reactions between bromonitro- alkanes andα,β-unsaturated ketones. We found that a chiral primary amine derived from natural quinine was efficient organocatalyst for the asymmetric nitrocyclo-propanations of bromonitroalkanes andα,β-unsaturated ketones for the first time. High enantioselectivities (83->99% ee) and diastereoselectivities (60:40-100:0) have been achieved. Moreover, we test in the kinetic resolution of racemic 4-substituted 2-cyclohexenones under the conditions typical for the asymmetric nitroclopro-panation.We also found that a chiral primary amine derived from natural quinine was efficient organocatalyst for the asymmetric Michael addition of N-heterocyles toα,β-unsaturated enone for the first times. High enantioselectivity (88-95% ee) has been achieved. Notably, mixing aromatic enones and 1H-benzotriazole with 4A molecular sieves furnished the desired adduct with excellent enantioselective.Moreover, we designed and synthesized four kinds of antimicrobial agent, they are pseudopeptidic macrolides, pseudopetides base L-tryptophan, amphiphilic cationic quinine-derived and complexes of valine-derived Schiff base. The obtained compounds were characterized by elemental analysis, FT-IR, NMR and X-ray diffraction. Biological studies of the obtained compounds had been carried out in vitro for antimicrobial activity against Gram-positive, Gram-negative bacteria and human pathogenic fungi. The compounds were proven to be broad spectrum agent, showed significant inhibition of the growth of the bacteiia and pathogenic fungi.