Study On The Preparation Of D-Histidine And D-Phenylglycine By Asymmetric Transformation

D-amino acids are widely used in the fields of food, pesticide, pharmacy and organic chemistry synthesis. D-histidine is a necessary amino acid for man and animal. D-phenylglycine is the important medicinal intermediate products of β-lactam antibiotics. L-histidine and DL- phenylglycine can be obtained by protein hydrolysates or chemical synthesis, while D-histidine and D-phenylglycine are difficult to obtained from natural products in large quantities and always be obtained by configuration transformation or resolution, therefore are very expensive. It is so necessary to conduct a full study on it.The procedures of D-histidine and D-phenylglycine preparation from L-histidine and DL- phenylglycine have been intensively studied.The 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, giving D-Histidine bitartarte. (98.69% yield, 98.26% optical purity). The optimum technological conditions are as follow: L-His:(R)-TA:salicyladehyde = l:l:0.05(mol), reaction temperature 90℃ and reaction time 4h.Treatment of the obtained salt D-histidine bitartarte with triethylamine of 2 mol ratio in methanol gave D-His with 92.87% total yield and 98.70%optical purity based on the starting L-Histidine.The asymmetric transformation of DL-phenylglycine via formation of salt with d-camphor sulfonic acid was carried out by using salicylaldehyde as a catalyst for epimerization in acetic acid, giving D-phenylglycine d-camphor sulfonic salt (85.90% yield, 99.80% optical purity). The optimum technological conditions are as follow: DL-phenylglycine: d-camphor sulfonic acid: salicyladehyde = l:1.05:0.02(mol), reaction temperature 80℃ and reaction time 5h.Treatment of the obtained salt D-phenylglycine d-camphor sulfonic salt with sodium carbonate gave crude D-phenylglycine. Crude D-phenylglycine was purified by isoelectric point method with 99.81% optical purity in 78.98% overall yield.