Preparation Of Three Special Amino Acids

D-proline,L-azetidine-2-carboxylic acid and L-tert-leucine are three kinds of special,non-protein amino acids,widely used in phamaceuticals,foods,pesticides and animal husbandry.Optically pure such amino acids can also be used as a chiral agent or catalyst in the chemical industry.General protein amino acids can be obtained by fermentation or protein hydrolysis.However,these three kinds of special amino acids are difficult to be obtained in large quantities from natural products,thus their prices are relatively high.In this paper,the racemization of amino acids were firstly studied,with the preparation of DL-amino acids.Then,the asymmetric transformation of L-proline was studied on the basis of racemization,and D-proline was prepared with high optical purity and high yield.Next,the racemic azetidine-2-carboxylic acid and tert-leucine were synthesized by chemical methods.On this basis,optically pure Z-azetidine-2-carboxylic acid and Z-tert-leucine is easy to be prepared in a high yield,which is suitable for industrial production.Finally,a preliminary exploration of the enzymatic resolution of racemic amino acids was carried out.We could successfully make the following conclusions:(1)The optimal conditions for the racemization reaction of Z-proline and Z-tert-leucine:with acetic acid as the solvent,n-butyraldehyde,n-heptylaldehyde or furaldehyde as the catalyst,and reaction temperature was 95℃ in the racemization of L-proline.With formic acid as a solvent,salicylaldehyde as a catalyst,and the reaction temperature was also 95℃ in the racemization of L-tert-leucine.The yield of DL-proline was 93.5%while the yield of DL-tert-leucine was 91.5%.The novel racemization of optically active amino acids in organic acid media is mild,easy to be controled without decomposition of amino acids in a high yield.Thus it is suitable for the racemization of most amino acids.(2)With L-proline as starting material,D-proline was prepared by asymmetric transformation.With propionic acid as solvent,n-heptaldehyde as catalyst,and D-tartaric acid as the resolution reagent.Under such conditions,the preparation has a high yield with high chemical and optical purity.The process is stable,repeatable and could be scaled up to one hundred grams scale.(3)The synthesis route of L-azetidine-2-carboxylic acid was performed.Based on the exploration of multiple routes and the optimization of the process,we made breakthrough progress,and successfully enlarged the process to one hundred grams scale.(4)The synthesis route of L-tert-leucine was performed.We resolved chemically synthesized racemic tert-leucine using chiral reagents,not only obtained L-tert-leucine,but also creatively obtained D-tert Leucine with high quality.This method is simple and is suitable for industrialization.(5)Three kinds of enzyme resolving substrates were synthesized,they are N-acetyl-DL-proline,N-acetyl-DL-azetidine-2-carboxylic acid and N-acetyl-DL-tert-leucine.The yields were 77.7%,89.5%,and 89.9%respectively.Preliminary investigations showed that natural aminoacylase activity is relatively low.There is no good results by enzymatic resolution.In the future process,it is necessary to screen new enzymes or increase enzyme activity.