Resolution Of Racemic Α-amino Acids Research Articles

Chromatographic resolution of racemic α-amino acids: Chiral stationary phase derived from modified xanthan gum

Enantiomeric resolution of α-amino acids into l-amino acid and d-amino acid via column chromatography using chiral stationary phase was performed. For this purpose, a dynamic chiral stationary phase prepared by grafting of methylmethacrylate onto xanthan gum (XG) was successfully employed in resolving various α-amino acids racemates. The peculiarities of the chromatographic behaviour of xanthan gum–graft-poly(methylmethacrylate)–amino acid interaction and the mechanism of their retention in column are discussed. The enantioselective properties of the xanthan gum–graft-poly(methylmethacrylate) in the separation of enantiomers of α-amino acids were studied using acidic solution of alanine, leucine, valine and tryptophan. The procedure is characterized by simplicity, efficiency and relatively low cost to analyze enantiomers of some amino acids.

Synthesis of New Chiral Crown Ethers Incorporating Two Different Chiral Units and 'Matched/Mismatched' Effect of the Two Chiral Units on the Chiral Recognition

Chiral crown ethers have been widely applied as chiral selectors in differentiating the two enantiomers of racemic compounds containing a primary amino group. Especially chiral crown ethers have been quite useful as chiral selectors of liquid chromatographic chiral stationary phases (CSPs) for the recognition of the two enantiomers of racemic primary amino compounds. Among a large number of chiral crown ethers, two types have been most successfully utilized as liquid chromatographic CSPs. The first type is chiral crown ethers incorporating chiral 1,1'-binaphthyl unit, which were first developed by Cram. Especially, chiral crown ethers such as bis-(1,1'-binaphthyl)-22-crown-6 immobilized on silica gel or polystyrene were used as CSPs in separating the enantiomers of racemic α-amino acids and their derivatives in the late 1970s by Cram and coworkers. Afterward, chiral crown ethers related to (3,3'-diphenyl-1,1'binaphthyl)-20-crown-6 (1, Fig. 1) dynamically coated on octadecyl silica gel or covalently bonded to silica gel were developed as liquid chromatographic CSPs and successfully utilized in the resolution of racemic α-amino acids and other racemic compounds containing a primary amino group. The second type of chiral crown ether successfully utilized as a chiral selector of CSPs is the one incorporating two tartaric acid units, (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (2, Fig. 1), which was first synthesized by Lehn and coworkers. Initially, (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (2) was utilized as a chiral selector for the chiral separation by capillary electrophoresis. The use of (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (2) was then extended as a chiral selector of liquid chromatographic CSPs. Liquid chromatographic CSPs based on (+)-(18crown-6)-2,3,11,12-tetracarboxylic acid (2) were very successful in the resolution of various racemic primary amino compounds or racemic non-primary amino compounds. In addition, (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid (2) was utilized as an NMR chiral solvating agent. However, chiral crown ethers incorporating both chiral 3,3'-diphenyl-1,1'-binaphthyl and tartaric acid unit have never been known to the best of our knowledge. Chiral crown ethers incorporating both chiral 3,3'-diphenyl-1,1'binaphthyl and tartaric acid unit are expected to show characteristics somewhat different from chiral crown ether 1 or 2 in the chiral recognition. In this study, we wish to report the synthesis of novel chiral crown ethers incorporating both chiral 3,3'-diphenyl-1,1'-binaphthyl and tartaric acid unit and their applications as chiral selectors of liquid chromatographic CSPs. We prepared actually two diastereomeric chiral crown ethers, (R,R,R)-3 and (R,S,S)-3 (Fig. 2), incorporating both (R)-3,3'-diphenyl-1,1'-binaphthyl and (R,R)or (S,S)-tartaric acid unit as chiral barriers. Combination of the two different chiral units as chiral barriers is expected to endow the two diastereomeric chiral crown ethers with characteristic chiral recognition ability according to the stereochemistry of the two chiral units. Synthesis of the two diastereomeric chiral crown ethers was successfully performed as shown in Scheme 1. Diols (R,R)-4 and (S,S)-4 prepared from commercially available (R,R)and (S,S)-N,N,N',N'-tetramethyltartaramide respectively via the known procedure were converted into their tosyl derivatives, (R,R)-5 and (S,S)-5. Tosylation of (R,R)-4 or (S,S)-4 was most successful when a small amount of 4(dimethylamino)pyridine (DMAP) was added to the reaction mixture. The cyclization of tosyl derivative (R,R)-5 or (S,S)-

The Thermodynamics of Lanthanide-Pipecolinate Complexation in an Aqueous Solution

The need to understand and develop novel complexes based on lanthanide ions with biologically active ligands has increased interest in them. The thermodynamics for the complexation and coordination environment of the complexes in solution are of utmost important in these systems to explain the biological activity of the species. For example, the coordination number and the presence of coordinated water molecules in complexes can affect the stability of the resulting complexes and the interaction between the lanthanide ions and ligands in an aqueous solution. With this in mind, we reported the thermodynamics of the complexation of trivalent lanthanide ions with cyclopentanecarboxlate, L-proline and substituted L-proline ligands. Based on the measured thermodynamic parameters, we proposed that lanthanide ions could be used in the resolution of racemic α-aminoacids. In this work, we have extended these studies to pipecolinate complexes in order to investigate the effect of the heterocyclohexyl ring in pipecolinate ligand on complexation in an aqueous solution. Potential and calorimetric titration were used to determine the stability and the enthalpy changes on complexation, and the nature of the binding behaviour was explained in terms of enthalpy and entropy changes.

Optical Resolution of Racemic α-Amino Acids on a Dynamic Chiral Stationary Phase Derived from (S)-Leucinol by Ligand Exchange Chromatography

Abstract A dynamic chiral stationary phase (CSP 7) for resolving racemic α-amino acids have been prepared by hydrophobically loading (S)-N,N-carboxymethyl dodecyl leucinol monosodium salt onto a commercial reverse phase octadecyl silica gel column. CSP 7 was successfully employed in resolving various racemic α-amino acids. The chromatographic results for resolving various racemic α-amino acids on CSP 7 have been found to be generally better as expected from the chiral recognition model proposed than those on the previously reported dynamic CSP (2), (R)-N,N-carboxymethyl dodecyl alaninol monosodium salt which is hydrophobically bound onto a commercial reverse phase octadecyl silica gel column. Especially, CSP 7 seems to be more attractive than CSP 2 in that CSP 7 shows reasonably good resolving ability for the broad range of racemic α-amino acids at the high content of organic modifier (20% CH3CN) in the aqueous mobile phase while CSP 2 shows very poor resolving ability.

Mechanistic evaluation of the resolution of α-amino acids on dynamic chiral stationary phases derived from amino alcohols by ligand-exchange chromatography

Two dynamic chiral stationary phases CSP 7 and 12) were prepared starting from R-2-amino-1-propanol and ( R)-α-phenylethylamine. The resolution of racemic α-amino acids on the two dynamic CSPs thus prepared were compared with previously reported resolution data on a dynamic CSP ( 2) derived from (1 S,2 R)-norephedrine. The enantioselectivity for the two enantiomers of α-amino acids on CSP 7 was found to be comparable to or better than that on CSP 2 while the enantioselectivity for the two enantiomers of α-amino acids on CSP 12 was much worse than that on CSPs 2 or 7. From these results, we concluded that the phenyl functionality at the first chiral center of CSP 2 is not essential in the chiral recognition. However, the hydroxy functionality of CSPs 2 or 7 does play a very important role in the chiral recognition.

Optical Resolution of Racemic α-Amino Acids on a Dynamic Chiral Stationary Phase by Ligand Exchange Chromatography

Abstract A dynamic chiral stationary phase for the ligand exchange chiral liquid chromatography was prepared by tentatively loading (1S, 2R)-N, N-carboxymethyl dodecylnorephedrine monosodium salt (4) prepared from (lS, 2R)-norephedrine onto a commercial reverse phase octadecyl-silica gel column and successfully used for the resolution of various amino acids without derivatization. The retention of the two enantiomers of amino acids on the column was found to be significantly influenced by the organic modifier content, Cu(II) concentration and pH of the mobile phase. However, the enantioselectivity was found to be significantly influenced mainly by the organic modifier content in the mobile phase. Based on the resolution trends of two enantiomers, a chiral recognition model concerning the enantioselective formation of ternary complex from the fixed ligand, amino acids and Cu(II) was proposed.

Ligand-exchange chromatography of racemates : XIII. Micropreparative resolution of l,d-leucine

Data are presented on the enantioselectivity and efficiency of ligand-exchange chromatographic resolution of racemic α-amino acids using a polystyrene resin with L-hydroxyproline groups and saturated with Cu 2+. Micropreparative resolution of L,D-leucine is discussed with respect to the degree of sorbent saturation with Cu 2+, elution rate, eluent concentration, operating temperature, column loading and column parameters.

Resolution of Racemic α-Amino Acids. II. Acidic α-Amino Acids

Resolution of Racemic α-Amino Acids. II. Acidic α-Amino Acids

Resolution of Racemic α-Amino Acids. I. Neutral α-Amino Acids

Resolution of Racemic α-Amino Acids. I. Neutral α-Amino Acids

The Resolution of Racemic α-Amino Acids

Publisher Summary This chapter focuses on the resolution of racemic α-amino acids. When same proteins are hydrolyzed by an alkaline agent, such as strong baryta, amino acids are optically inactive and posses different solubilities from those of the corresponding active forms. These values are obtained with amino acids isolated from proteins after acid hydrolysis. When the same proteins are hydrolyzed by an alkaline agent, such as strong baryta, the amino acids are optically inactive and possessed somewhat different solubilities from those of the corresponding active forms. The final step demonstrates that the optically inactive form of these amino acids is in a racemic mixture of two optical enantiomorphs, one of which is the natural form of the amino acid isolated from protein hydrolysates.