Synthesis Of Proline Derivative Of Its Application In The Asymmetric Reduction Of Dihydro Papaverine

Asymmetric synthesis has recently become a hot topic in organic synthesis. With its continuous development, the asymmetric reaction has been used in asymmetric reduction, asymmetric alkylation, asymmetric oxidation and asymmetric condensation reaction. It has brought huge economic benefits for people in research fields such as medicine, chemistry, life sciences, food additives, spices and the like, which has attracted more and more attention from chemists.Catalytic asymmetric hydrogenation of isoquinoline alkaloids is one of the most direct and efficient methods for the synthesis of tetrahydroisoquinoline alkaloids. At present, according to the reports in most of the literature, catalytic asymmetric hydrogenation of dihydroisoquinoline alkaloids predominantly employs organometallic catalysts complexed by chiral ligands and transition metals. Although progresses have been made with these catalysts regarding catalytic asymmetric hydrogenation of dihydroisoquinoline alkaloids, there are still some problems, such as costliness, poor stability, difficult to recycle and hard reaction conditions.Organocatalysts are an important class of chiral catalysts developed after organo-metallic catalysts, which have unique advantages compared with the organometallic catalysts and enzyme catalysts. Presently, proline and its derivatives as organocatalysts are among the most widely and successfully used chiral catalysts. The basic idea of our work is to design and synthesize a series of proline derivatives, which are complexed with sodium borohydride and used in catalytic asymmetric hydrogenation of dihydroiso-quinoline alkaloids, and to investigate the effects of catalytic hydrogenation.The main work of this thesis composes of the following parts:1. We synthesised three kinds of4-substituted proline derivatives from (2S,4R)-N-Boc-hydroxy-proline by etherification reaction.(2R)-proline reacting with terephthalic acid, cinnamic acid, benzyl bromide respectively, generated terephthaloyl-(2R)-proline, E-cinnamyl-(2R)-proline and (2R)-N-Bn-proline.2. The target compounds were synthesized by firstly esterification of (2S/2R)-proline, followed by condensation with (2R)-N-Boc-proline,(2S,4R)-N-Boc-4-hydroxyl-proline, (2S,4R)-N-Boc-4-benzyloxy-proline,(2S,4R)-N-Boc-4-p-methyl-benzyloxy-proline and (2S,4R)-N-Boc-4-p-bromine-benzyloxy-proline, respectively, and ester hydrolysis to give nine catalysts of prolinedipeptide. There are six novel compounds that have never been reported in the literature, which also provide some reference for the future research in the field.3. The complexes formed with the above-synthesized proline derivatives and sodium borohydride were used in catalytic asymmetric hydrogenation of dihydropapaverine to explore the effects of the catalytic hydrogenation. Finally, combined with the molecular structure of catalysts and reaction mechamism, we analysed the cause of poor catalytic hydrogenation effects and obtained the preliminary conclusions.