Study On Preparation Process Of D-amino Acids By Crystallization-induced Asymmetric Transformation

D-amino acid is one kind of amino acids,which construction is opposited to nature L-amino acid,and it is mainly obtained by synthetic.The Drugs that contain D-amino acid usually show a good inhibiting and killing effect on bacteria,fungi,germs,and tumor cells.With the increasing demands on optical purity of D-amino acid in polypeptide new drugs and antiviral drugs and the growing market demand,studying new method of preparing D-amino acid,solving basic problems in the existing production technology have important meaning in improving the production efficiency and optical purity of D-amino acid,and it's a important part of polypeptide drugs and antiviral drugs research.Based on copious literature,D-proline?D-phenylalanine and D-valine were prepared by asymmetric transformation with D-tartaric acid and?+?-1-phenylethyl sulfonic acid as chiral reagents in this paper.The influencing factors of asymmetric transformation process were studied such as solvent,catalyst,solid-liquid ratio,temperature,and stirring way,which has very important in theoretical and realistic significance.The condition for preparation of D-proline·D-tartaric acid?92%e.e.?with yield of98.9%was as follows:the mole ratio of L-proline,D-tartaric acid and n-butanal is 1:1:0.1in n-butyric acid as solution,solid to liquid ratio is 1:13,refluxing for 8 h.D-proline·D-tartaric acid salt was dissolved in methanol,the solid to liquid ratio is 1:10,mechanical stirring with NH₃ adjusting pH to 10,then filteration,D-proline?99.9%o.p.?was obtained by concentrating filtrate with the yield of 95.6%.The resolution reagent can be recycled for use.The condition for preparation of D-phenylalanine·D-tartaric acid?91.4%e.e.?with yield of 96.6%was as follows:the equivalence of DL-phenylalanine,D-tartaric acid and salicylaldehyde is 1:1:0.15 in propionic acid,solid to liquid ratio is 1:12,refluxing for 8 h.D-phenylalanine·D-tartaric acid salt was dissolved in 90%methanol,the solid to lid ratio is1:7,mechanical stirring then filteration,D-phenylalanine?95.7%o.p.?was obtained with the yield of 83%.The resolution reagent can be recycled for use.The condition for preparation of D-valine·?+?-1-phenylethyl sulfonic acid?92%e.e.?with yield of 98.9%was as follows:the equivalence of DL-valine,?+?-1-phenylethyl sulfonic acid and n-butanal is 1:1:0.1 in acetic acid as solution,solid to liquid ratio is 1:10,refluxing for 8 h.D-valine·?+?-1-phenylethyl sulfonic acid was dissolved in water,the solid to liquid ratio is 1:1.5,mechanical stirring with triethylamine adjusting pH to 5.96,then filteration,D-valine?99.6%o.p.?was obtained with the yield of92.3%.The resolution reagent?+?-1-phenylethyl sulfonic acid can be recycled for use.D-proline was prepared via dissolution the salt D-proline·D-tartaric acid by NH₃,it can avoid introducing too much water to the reaction system,which is benefit to concentrating product.This method is easy to operate,low cost and high-yield which is not found in references,and it is an important innovation in this paper.In addition,during the process of preparation of D-phenylalanine we found that the salt D-phenylalanine·D-tartaric acid salt can be dissolved in methyl alcohol solution,the yield of D-phenylalanine was 83%,and D-phenylalanine was obtained by ultrasonic method in methyl alcohol with the yield of 95%.Compared with the traditional dissociation process of complex salts,this method can reduces the use of acid and alkali and avoids the production of inorganic salt.The process is environmentally friendly,easy to operate,which is not found in references,and it is another important innovation in this paper.