Study On Synthesis Of The Novel 2,3-pyridine-dione

Hydroxypyridinone derivatives exhibit various biological activities such as antibacteria,anti-inlfammatory,antimalarial,cardiotonicagents,antihypetrensive,antineoplastic,analgesicefect and favourable effect in Parkingson'sdisease and so on .Since Hydroxypyridin-one derivatives are selective for iron(III) and oralactivity,They are a kind of ideal iron-scavenging agents.Especially,1,2-dimethyl- 3-hydroxy-4-pyridinone(Deferiprone,Ll)has shown powerful effect for the treatment of Thalassemia disease in clinic.Due to the deferoxamine has some disadvantages such as expensiveness,oral inactivity and short half life in plasma,the pyridinone derivatives have become their main alternatives.In this thesis,a series of new 2,3-pyridine-dione derivatives were synthesized by Oxidation-Michael Addition reaction and Mannich reation, and their active mechanism was discussed。The optimum synthesis conditions were obtained such as the materials ratio, the reaction time, the reation temperature and the amount of oxidant .The main results are shown as follows:1,A series of 5,6-asymmetrical substituted-2,3-pyridine-dione derivatives were synthesized by Oxidation-Michael Addition method , their structures were characterized by IR,1H NMR,MS,13C NMR,HMQC,HMBC and COSY. We confirmed the structure of 5-(4-methoxyphe-nylamino)-6-(phenylamino)pyridine- 2,3-dione by crystal difraction.It is demonstrated that the nucleophiles can attack the 5-position and 6-position of pyridinering in the Oxidaiton-Michael Addition reaction and the additive products exist in the form of 2,3- pyridine–dione.2,By Oxidation-Michael Addition method and Mannich reaction, We have synthesized a series of 4-substituted-5,6- disubstituted-2,3-pyridine-dione derivatives.and optimized the condition of the reaction.The optimum reaction conditions are obstained: the molar ratio of reactants being 1:1.5:1.5, reaction temperature being 45℃and reaction time being 24h. Under this condition, the yields of reaction were up to 58.1%.3,We have obtained two 4-iodide-5,6- disubstituted-2,3-pyridine-dione derivati-ves by the iodide reaction of 5,6- disubstituted-2,3-pyridine-dione derivatives and the reactive mechanism was discussed.On the study of synthesis reaction condition ,we found the yield of the reaction is highest when 10% of L-Hydroxyproline was used for catalytic.