Studies On Racemization And Asymmetric Transformation Of L-Histidine And L-Proline

Histidine and proline are necessary amino acids for man and animal. Optical active histidine and proline are useful as chiral reagents and catalysts in asymmetric syntheses. Also, they are used in the fields of pharmacy, food and chemistry. The main configurations of animo acids are DL-, L- and D-. L-histidine and L-proline can be obtained by fermentation or by isolation from protein hydrolysates. However, D-histidine and .D-proline are difficult to obtained from natural products in large quantities and, therefore, are very expensive.In this article, the racemizations of L-proline and L-histidine were studied. Based on the results of racemization, we studied the asymmetric transformation of L-proline and L-histidine.L-proline and Z-histidine could be racemized in carboxylic acids used as solvents in presence of catalytic amounts of aldehydes such as butanal and salicyladehyde. The racemizations were found to follow first-order reaction kinetics. The rate constant of racemization of Z-Pro increased with decreasing acidity of the carboxylic acid. However, the rate constant of racemization of Z-His was most rapid in acetic acid. The water in carboxylic acid decreased the rate of racemization. When the temperature increased, the rate constant of racemization increased. For Z-Pro, the relation between the rate constant of racemization and its reaction temperature was proposed as follow:The appropriate aldehyde used as a catalyst for the racemization of L-Pro and L-His should be butanal and salicyladehyde, respectively. Salicylaldehyde and butanal gave a sufficient racemization degree in the use of 0.1 molar equivalent. The mechanism of the racemization was discussed. DL-histidine and DL-proline were obtained by racemization in 91.83 % and 84.78% yield respectively.An asymmetric transformation from L-histidine to D-histidine through formation of salt with (R)-tartaric acid was achieved by using Salicylaldehyde as a catalyst for epimerization in acetic acid. The appropriate reaction time for the asymmetric transformation is 5 h at 80 and 3 h at 90 . The presence of water in acetic acid decreased the yield and optical purity of D-histidine bitartrate. In additon, the appropriate concentration of the starting L-histidine in acetic acid used as solvent was 12.4%w/v. The rate of epimerization of the D-histidine bitartrate by using of Salicylaldehyde as the catalyst was larger than that by butanal. The optimal molar ratio of the Salicylaldehyde to starting L-histidine is 0.1. Treatment of the obtained salt with triethylamine in methanol gave D-His with 100% optical purity in 93.71% yield based on the starting L-histidine.The asymmetric transformation of L-proline via formation of salt with (S)-tartaric acid was carried out by using butanal as a catalyst for epimerization in butanoic acid. Through orthogonal experiments, the optmum reaction condition for the asymmetric transformation of L-proline was obtained. Under this optimum condition,D-Pro-(S)-tartaric acid salt was obtained with 100% optical purity in 92.45% yield. Treatment of the obtained salt with aqueous ammonia(35%) in methanol gave D-His with 100% optical purity in 85.62% yield based on the starting L-histidine..