Synthesis Of The Derivates From Amino Acid

The dissertation consisted of five parts: (1) study on the synthesis of DL-serine ethers, (2) preliminary test of the asymmetric synthesis of serine ethers, (3) synthesis of Gly-Gly-OEt" HC1, (4) synthesis of ornithine aspartate, (5) synthesis of Arg-OEt" HC1.1. Study on the synthesis of DL-serine ethers(1) A new route for synthesis of DL-serine ethers was designed. Using methyl acrylate as starting material, DL-Serine ethers were prepared through five steps, including epoxidation, ring-opening with alcohols, protection of hydroxyl, hydrolysis of methyl ester and ammonolysis.(2) Several DL-Serine ethers, including methyl ether, ethyl ether and tert-butyl ether, were synthesized successfully with 31% of total yield using different ring-opening reagent.(3) Compare with the current methods for biological synthesis of DL-serine derivatives, the new route has many advantages, for example, the original material was cheap and the expensive materials, such as iodomethane, Pd/C were avoided, and the process was not sensitive to oxygen and water and easy to operate.2. Preliminary test of asymmetric synthesis of serine ethers.(1) Asymmetric ring-opening of methyl oxirane-2-caboxylate using Jacobsen catalyst gave (R)-2-hydroxy-3-benzoxypropenoic acid with 66% yield. Although the ee% value of 2-hydroxy-3-benzoxypropenoic acid was only 42%, it was the first time preparing optical serine ethers by asymmetric synthesis.(2) Different catalytic systems, such as poly (L-leucine) AJHP/ DBU, poly (L-leucine) /sodium percarbonate, chiral ketones /H2O2, chiral ketones / Oxone, were tested for the asymmetric epoxidation of methyl acrylate.3. Synthesis of Gly-Gly-OEt HC1Gly-Gly-OEt HC1 was prepared by four steps, protection of amino group,protection of carboxyl group, condensation and deprotection reaction. The solvent and temperature effect for condensation were tested. The results showed that high yield (88%) could be obtained at -10~-5℃ in CH2C12.4. Synthesis of ornithine aspartateOrnithine, an unstable amino acid, was freed from its hydrochloride through ion exchange resin. The reaction of the in situ freed ornithine with asparagic acid gave the drug material ornithine aspartate5. Synthesis of Arg-OEf HC1The esterification of arginine was investigated. Ethyl Argininate hydrochloride was successfully synthesized as solid using thionyl chloride.