Research Of Cinchona Alkaloids Derivative Catalytic Asymmetric Reaction And Its Application In Synthesis Of Chiral Drug

Recently, as the development in asymmetric synthesis and enantiomerically pure materials are playing more significant role in medical, agriculture and intermediates, asymmetric organic catalysis has become a hot topic in chemistry. Compared with the traditional transition metal complex catalysts, the organic catalyst is cheap, easy to get, non-toxic, high activity and reusable. Cinchona alkaloid has multiple chiral centers, the unique three-dimensional conformation, hydrophilic hydroxyl, electronic effect, the complexity of the structure and other characteristics that make it show a great potential in asymmetric catalysis .Construction of the new catalysts in asymmetric catalysis occupy a very important position. Owing to cinchona alkaloids the unique three-dimensional structure, associated with metals, they are widely used in asymmetric organic catalytic reactions. Based on cinchona alkaloid, we design and synthesize three new chiral catalysts. And they are used in asymmetric organic catalytic reactions such as IFB reaction, Michael addition reaction, AD reaction.etc. Because of their wonderful performance in AD reaction, we successfully explore a environment-friendly route to synthesize drug IDHP that treat cardiovascular and cerebrovascular diseases, enantioselectivity up to 97% ee.My work is as follows:1. Twelve novel chiral catalysts were synthesized from QN, QD, DHQN and QHQD.2. The synthesized catalysts induce IFB reaction involving inβ-bromoketoesters and 1,3-dione. THF as solvent, -78℃, B4 (DHQD) induced catalysis, enantioselectivity up to 98.4% ee.3. The synthesized catalysts induce Michael addition reaction involving inβ,γ-unsaturated-α-ketoesters and 1,3-dione. Toluene as solvent, -20℃,10%mol catalyst and A4 (DHQD) induced catalysis, enantioselectivity up to 98.4% ee.4. Based on the synthesized catalysts outstanding performance in the asymmetric dihydroxylation reaction. we successfully explore a simple, environment-friendly route of synthesis of optically pure IDHP, enantioselectivity up to 97.8% ee.