The Synthesis And Chiral Resolution Of DL-phenylalanine And Its Derivatives

The contents of the dissertation mainly are the preparation and resolution methods of DL-phenylalanine and its derivatives which consist of five parts: 1. study on the synthesis of DL-phenylalanine, p-Cl-DL-phenylalanine and p-Br-DL-phenylalanine. 2.preliminary test of the synthesis of p-I-DL-phenylalanine. 3. study on the enzymatic resolution. 4.study on the chemical resolution. 5.synthes is of unnatural chiral amino acid N-Fmoc-L-β-phenylalanine.1. Study on the synthesis of DL-phenylalanine, p-Cl-DL-phenylalanine,and p-Br-DL-phenylalanine(1)Through the systemic study on the synthetic route of DL-Phe in the literature,Meerwine reaction was considered to be the most attractive route to synthesis DL-Phe from the cheap and facile aniline via this four-step procedure:diazotization,acrylonitrile addition,nitrile hydrolysis,ammonolysis.(2)Basic on the synthesis of DL -Phe, p-Cl-DL-Phe and p-Br-DL-Phe were prepared from raw materials p-chloro-aniline and p-bromo-aniline respetively.The effect of reaction variables including different reaction solvent and temperature were investigated to greatly improve the product yield to 80%.(3)The point of the part was to optimize the reaction condition to improve the product yield , reduce the cost ,simplify the production process and exploit a suitable industrial technology.2. Preliminary test of the synthesis of p-I-DL-phenylalanineIodo compounds were unstable under high temperature and basic circumstances,and there was no related literature about the preparation in Meerwine arylation.A new route for synthesis of p-I-DL-Phe was designed and tried,and finally a five-step procedure including nitration,reduction,chelating, diazotization and iodonation was adopted to synthesis directly from L-Phe.Pd/C reduction reaction was tried to be substituted by cheap Fe power reduction,but the result was not as good as we expected.3. Study on the enzymatic resolution...