title: Chiral ligand-exchange high-performance liquid chromatography with copper (II)-L-phenylalanine complexes for separation of 3,4-dimethoxy-α-methylphenylalanine racemes.
abstract: L-3, 4-dimethoxy-α-methylphenylalanine (L-DMMD) is an important intermediate for the synthesis of 3-hydroxy-α-methyl-L-tyrosine (L-methyldopa). This paper describes an efficient, accurate, and low-priced method of high-performance liquid chromatography (HPLC) using chiral mobile phase and conventional C18 column to separate L-DMMD from its enantiomers. The effects of ligands, copper salts, organic modifiers, pHs of mobile phase, and temperatures on the retention factors (k') and selectivity (α) were evaluated to achieve optimal separation performance. Then, thermal analysis of the optimal separation conditions was investigated as well. It was confirmed that the optimal mobile phase was composed of 20 % (v/v) methanol, 8 mM L-phenylalanine (L-Phe), and 4 mM cupric sulfate in water of pH 3.2, and the column temperature was set at 20 °C. Baseline separation of two enantiomers could be obtained through the conventional C18 column with a resolution (R) of 3.18 in less than 18 min. Thermodynamic data (∆∆H and ∆∆S) obtained by Van't Hoff plots revealed the chiral separation was an enthalpy-controlled process. To the best of our knowledge, this is the first report regarding the enantioseparation of DMMD by chiral ligand-exchange HPLC.
authors.affiliation: Institute of Bioengineering, Zhejiang University of Technology, 18 Chaowang Road, Hangzhou, 310014, China.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Jia
authors.forename: Zheng-Gui
authors.initials: ZG
authors.lastname: Ai
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Xue
authors.forename: Yu-Guo
authors.initials: YG
authors.lastname: Zheng
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002852:Chromatography, Ion Exchange / Q000379:methods*; D008024:Ligands; D059625:Liquid-Liquid Extraction / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D008024:Ligands; D009942:Organometallic Compounds; C549188:copper (II) N,N-dimethyl-L-phenylalanine; C062533:3,4-dimethoxy-alpha-methylphenylalanine; D010649:Phenylalanine