Optical Resolution Of Amino Acids Research Articles

Efficient optical resolution of amino acid by alanine racemaze chiral analogue supported on mesoporous carbon

Optically pure D-amino acids are industrially important chiral building blocks for the synthesis of pharmaceuticals, food ingredients, and drug intermediates. Chemoenzymatic dynamic kinetic-resolution processes have recently been developed for deracemization of amino acids. S-ARCA would be a good candidate for the selective adsorption of D amino acid through the imine formation reaction. The organic phase containing S-ARCA adsorbent, TPPC or Ionic Liquid (as a phase transfer catalyst) in MC were coated on the surfaces of mesoporous carbon C-SBA-15(CMK). The aqueous solution of racemic D/L-amino acid and NaOH were added to the carbon support coated with ARCA. The D/L ratios on ARCA and in solution were determined with increasing reaction time. S-ARCA has a unique property for the selective adsorption of D- amino acid (up to 90% selcetivity) in the racemic mixture. The fixed bed reactor containing ARCA/carbon support was also adopted successfully for the selective separation of amino acid.

Optical resolution of phenylalanine using D‐Phe‐imprinted poly(acrylic acid‐co‐acrylonitrile) membrane—Racemate solution concentration effect

AbstractA novel nanoporous molecularly imprinting copolymer [Poly(acrylic acid‐co‐acrylonitrile)] membrane (DICMI) has been synthesized by the wet phase inversion method, using D‐Phenylalanine as template, for the optical resolution of amino acid. The membrane prepared is intended for the selective separation of phenylalanine. The racemate solutions of different concentrations (10‐ppm, 50‐ppm, 100‐ppm, and 200‐ppm) were filtered through the membrane fixed in an ultrafiltration kit at 98 kPa pressure to investigate the concentration effect on optical resolution of amino acid using DICMI. Adsorption selectivities of 0.37, 0.45, 0.57, and 0.71 were achieved after 25 ml of filtration of 10‐ppm, 50‐ppm, 100‐ppm, and 200‐ppm racemate solutions respectively. Scanning electron microscopy was used to study the morphological structure of membrane. Chemical structure was studied by Fourier transmission infrared spectroscopy. POLYM. COMPOS., 2008. © 2008 Society of Plastics Engineers

Optical resolution of amino acid by ultrafiltration through immobilized DNA membranes

Ultrafiltration experiments for the optical resolution of racemic phenylalanine were investigated in a DNA solution system and by using immobilized DNA membranes. L-phenylalanine preferentially existed in the permeate solution and D-phenylalanine preferentially existed in the concentrate solution in the ultrafiltration of racemic phenylalanine through the immobilized DNA membranes. This indicates that L-phenylalanine preferentially enters into the pores of the immobilized DNA membranes and permeates through the membranes due to the interaction between DNA and L-phenylalanine. The immobilized DNA membranes were categorized as channel type membranes.

Optical resolution of amino acid by ultrafiltration using recognition sites of DNA

Ultrafiltration experiments for the optical resolution of racemic phenylalanine were investigated in a DNA solution system and by using immobilized DNA membranes. d-Phenylalanine preferentially existed in the totally collected permeate solution in the ultrafiltration of DNA and racemic phenylalanine solution (i.e. DNA solution system), although the separation factor ranged from more than unity or less than unity depending on the permeation time when the concentration of DNA was less than 0.5 ppm. This is explained by the fact that DNA sometimes releases phenylalanine depending on the permeation time in the dilute DNA solution (i.e. 0.01–0.5 ppm) due to the conformational change of DNA as a function of time. On the other hand, l-phenylalanine preferentially existed in the permeate solution and d-phenylalanine preferentially existed in the concentrate solution in the ultrafiltration of racemic phenylalanine through the immobilized DNA membranes. This indicates that l-phenylalanine preferentially enters into the pores of the immobilized DNA membranes and permeates through the membranes due to the interaction between DNA and l-phenylalanine. The immobilized DNA membranes were categorized as channel type membranes.

Novel Optical Resolution of Phenylalanine Racemate Utilizing Enzyme Reaction and Membrane Extraction

A novel optical resolution method for d,l-phenylalanine in which an enzyme reaction and a membrane extraction are combined has been designed. In the first stage only the l-isomer of the racemic phenylalanine methyl ester was selectively hydrolyzed by the enzyme α-chymotrypsin. Further, the unreacted ester was selectively recovered from the mixture of the transferred amino acid and the ester form by a membrane extractor. Effects of operation conditions in the enzyme reaction and the membrane extraction on the separation efficiency were investigated. The pH in the material sources is found to be an important factor in the activity and selectivity for the enzymatic resolution. A novel immobilized enzyme enables the expensive enzyme to be reused in the feed solutions. The hollow-fiber membrane extractor was a good separator for an amino acid and its ester derivative, because only the ester was selectively extracted into an organic phase. The novel separation system becomes a very useful process for the optical resolution of amino acids by combining the enzyme reaction with a membrane extraction.

Effect of surfactant agents and lipids on optical resolution of amino acid by ultrafiltration membranes containing bovine serum albumin

Ultrafiltration experiments for the optical resolution of racemic phenylalanine were performed in a solution system containing bovine serum albumin (BSA) and surfactant agents (Triton X-100, Tween 20, sodium dodecyl sulfate), lipid (phosphaticylcholine) and fatty acid (palmitic acid sodium salt). It was found that d-phenylalanine preferentially existed in the permeate at pH 7.0 due to the binding of BSA to d-phenylalanine in the feed and that the separation factors (=concentration ratio of d-isomer to l-isomer in the permeate) increased with a decrease in the BSA solution containing no additives and in the BSA solution containing Triton X-100 or Tween 20. The unusual tendency that the separation factors were less than unity was observed and the separation factors decreased with a decrease in the feed concentration of phenylalanine during the ultrafiltration containing the palmitic acid sodium salt or the phosphatidylcholine. This is caused by the fact that the binding constants of d-phenylalanine to BSA are higher than those of l-phenylalanine in the BSA solution containing the palmitic acid sodium salt or phosphatidylcholine. Since there were found conformational changes of BSA in the presence of palmitic acid sodium salt based on circular dichroism measurements of BSA solution, the conformational changes of BSA were attributed to the higher affinity of d-phenylalanine to BSA than that of l-phenylalanine in the BSA solution containing the palmitic acid sodium salt or phosphatidylcholine.

The optical resolution of amino acids by plasma polymerized terpene membranes

Four kinds of terpenes, i.e. l-menthol, S-(−)- β-citronellol, [(1 S)-endo]-borneol, and R-limonene, were fixed on a cellulose acetate membrane by plasma polymerization method at various periods of plasma irradiation. The fractional fixations of terpenes increased with increasing time of plasma irradiation. The optical resolutions of racemic tryptophan ( dl-Trp) solutions were performed by the dialysis and the ultrafiltration using the plasma polymerized membranes. All the membranes were permeable with respect to the d-isomer tryptophan in in preference to the l-isomer. The larger value of separation factor was obtained at lower volume flux. The maximum value of separation factor obtained for dl-Trp was 9.5 at volume flux J v=4.7 × 10 −8 m s −1. The solute permeabilities and apparent viscous parameters were evaluated from the dialysis and ultrafiltration data, respectively. A linear relation between the solute permeability and the ratio of apparent viscous parameters was obtained. It is indicated that the strength of chemical interaction between the amino acid solute and the terpene fixed in the membrane has a high influence on the solute flow inside the membrane pore.

Molecularly Imprinted Polymeric Membranes Containing DIDE Derivatives for Optical Resolution of Amino Acids

Molecularly imprinted polymeric membranes, bearing the tetrapeptide derivative H−Asp(OcHex)−Ile−Asp(OcHex)−Glu(OBzl)−CH2−, were prepared during the membrane preparation (casting) process in the presence of print molecule Boc−l-Trp. The molecularly imprinted membranes thus obtained showed adsorption selectivity toward a print molecule family, such as l-Trp, l-Phe, l-Ala, l-Arg, and l-Glu. The tetrapeptide derivative in the molecularly imprinted membranes preferentially recognized the l-amino acid from the d-isomer. Enantioselective permeation was attained with the present membrane, and the d-isomer was permeated in preference to the l-isomer by using the concentration difference as a driving force for membrane transport. Electrodialysis of racemic amino acid showed the possibility that permselectivity directly reflects its adsorption selectivity. It was made clear that the optical resolution was attained by the molecularly imprinted polymeric membranes.

Separation Properties of Enantiomeric Amino Acids by Ultrafiltration Using Cyclodextrin.

The new separation method based on the selective inclusion properties of cyclodextrin (CD) for structural isomers and selective permeability of ultrafiltration were applied to the optical resolution where the selective inclusion of enantiomers by CD is the key step. Permeation experiments were carried out with enantiomers of threonine and phenylalanine. Some informations about the optical resolution of amino acids by the presented method were obtained.

Optical Resolution of Amino Acids and Mandelic Acid by Complex Formation with Copper(II) Ion

Abstract The optical resolutions of amino acids and mandelic acid (MA) are done by complexation with copper(II). The optical purity of MA is the best when phenylalanine is used, i.e. 81%, and phenylglycine (PG) is well resolved by using l-MA with the optical purity of 74%. These results are interpreted in terms of the optical absorption energies of the copper(II) complexes in aqueous solution.

An information theory-based evaluation of stationary phases developed for optical resolution of amino acids

Naphthylethylurea multiple-bonded chiral stationary phases prepared for the optimal resolution of p-bromophenylcarbamyl derivatives of enantiomeric amino acids are examined from the viewpoint of information theory. The criterion used is the function of mutual information (FUMI) which describes the precision of analysis as a function of peak shape (area and width), overlap and noise level. The length of the polyethyleneamine spacer in the chiral stationary phases is evaluated by the precision (FUMI) calculated from the peak shape and overlap. The best column is defined as the one which gives the highest precision. The temperature effect on the precision is also examined.

Preparation of cellulose stilbene-4-carboxylate and its application to thin-layer chromatography

Photoreactive cellulose stilbene-4-carboxylate (SB-cellulose) with degrees of substitution of up to 1.9 has been prepared by the reaction of regenerated amorphous microcrystalline cellulose with stilbene-4-carbonyl chloride. The stilbene moiety in the SB-cellulose was found to undergo an isomerization from trans to the more polar cis form under irradiation with UV light, resulting in an increase in the swelling ability of the SB-cellulose in water. Application of the SB-cellulose as an adsorbent in thin-layer Chromatography (TLC) was examined. The separation of the spots of appropriate hydrophobic dyes in the TLC was improved using the SB-cellulose as a component of the adsorbent, and more so by irradiation with UV light. Application of this method to the optical resolution of amino acids is suggested as a promising technique for some amino acids such as phenylalanine.

セルロース系光機能性材料の開発の試み

General examples of optically functional polymers are shortly reviewed, and then our investigations on development of cellulosic optically functional materials are described. Photoresponsive behaviors of cellulose p-phenylazobenzoate (AB-cellulose) as a photoresponsive material, which is reversibly isomerized under photoirradiation, are investigated and its swelling ability, contact angle with water, and formation of liquid crystalline phase are found to be controlled reversibly under irradiation with UV and visible lights, and optical resolution of amino acids appears to be also controlled in the thin layer chromatography using AB-cellulose as an adsorbent. Photoreactive behaviors of cellulose cinnamate as a photoreactive materials, in which the photoreaction is irreversible, are investigated and intermolecular cross-linking, fixation of liquid crystalline structure, and increase in physical strength of the cellulose cinnamate under irradiation with UV light are confirmed. Cellulose has some excellent inherent properties and is expected to be a raw material for development of new fuctional materials.

Unusual solvent effect on protease activity and effective optical resolution of amino acids by hydrolytic reactions in organic solvents

The catalytic activities of α-chymotrypsin, subtilisin Carlsberg, and subtilisin BPN' for hydrolysis of amino acid esters in acetonitrile-water were unusually dependent on the solvent composition. The products obtained as precipitates in high concentrations of acetonitrile were L-amino acids of high optical purities, and effective optical resolution of amino acids was achieved.

Optical resolution of amino acid and hydroxycarboxylic acid esters by complexation with optically active host compounds: a crystallographic result

Selected esters derived from amino and hydroxycarboxylic acids have been resolved by inclusion complexation with optically active host compounds derived from tartaric acid. The crystal structure of the inclusion compound I(R,R)-(–)-trans-2,3-bis(hydroxydiphenylmethyl)-1,4-dioxaspiro[4.4]-nonane·½(methyl 3-hydroxybutanoate) is reported. I[(C33H32O4)2·C5H10O3] is monoclinic P21, a= 9.176(2), b= 39.70(2), c= 9.216(2)Å, β= 119.45(1)°, V= 2923(2)Å3. The structure was solved by direct methods and refined to a final R value of 0.037. Host and guest molecules are linked by hydrogen bonding.

Optical resolution of amino acids, peptides and hydroxycarboxylic acids using a new chiral column for ligand-exchange chromatography

The enantiometric resolution of amino acids, amino acid derivatives, peptides and hydroxycarboxylic acids was investigated using a chiral column of the ligand- exchange type. It was found that this column separated all of these compounds satisfactorily. Columns containing either a d- or l-ligand gave almost identical chromatograms, except that the retention order for a pair of chiral isomers was reversed. These columns could be applied to resolve simultaneously ten different types of dL- amino acids. Optically active impurities present in d and l-amino acids could be determined at concentrations down to about 100 ppm.

ChemInform Abstract: A Novel Chiral Stationary Phase for Optical Resolution of Amino Acids and Their Derivatives by Ligand‐Exchange High‐Performance Liquid Chromatography.

AbstractA novel chiral stationary phase, the acid corresponding to the salt (III), is prepared from (‐)‐norephedrine (I) and the salt (III) is bound to silica gel pretreated with (3‐(glycidyloxy)propyl)trimethoxy silane (→ (IV) → (V) → (VI)).

A Novel Chiral Stationary Phase for Optical Resolution of Amino Acids and Their Derivatives by Ligand-Exchange High-Performance Liquid Chromatography

Abstract A novel chiral stationary phase, [(1R,2S)-2-hydroxy-1-methyl-2-phenylethylamino]acetic acid, was prepared from (−)-norephedrine, and its sodium salt was bound to silica gel pretreated with [3-(glycidyloxy)propyl]trimethoxysilane. The chiral stationary phase was found to be effective for the optical resolution of amino acids and their derivatives by ligand-exchange high-performance liquid chromatography using aq copper(II) sulfate solution as an eluent.

Novel chiral stationary phases for optical resolution by ligand-exchange high-performance liquid chromatography

Novel chiral stationary phases, (1 R,2 S)- and diastereomeric (1 S,2 S)-2-carboxymethylamino-1,2-diphenylethanol, were prepared from (1 R,2 S)- and (1 S,2 S)-2-amino-1,2-diphenylethanol, respectively, and were bound to silica gel pretreated with 3-glycidoxypropyltrimethoxysilane. The chiral stationary phases were found to be very effective for the optical resolution of amino acids, amino acid derivatives and hydroxy acids by ligand-exchange high-performance liquid chromatography.

シクロデキストリン残基を有する高分子膜によるアミノ酸の光学分割

高分子膜を透過させることによりDL-アミノ酸を光学分割することを目的として,側鎖に分子包接能を有するβ-シクロデキストリン残基を導入した高分子を合成し,これから得られる高分子膜のアミノ酸透過性を検討した。フェニルアラニンを透過させた場合,L-体の透過速度がD-体にくらべて大きく,その透過係数比は1.40であった。トリプトファン,ヒスチジンを透過させた場合も同様の傾向となった。また,シクロデキストリン残基のかわりにグルコース残基を有する高分子膜を用いた場合は,アミノ酸の光学異性体間で透過係数に差は認められない。さらにβ-ジグロデキストリンを橋かけした樹脂に対するフェニルアラニンの吸着量は,L-体にくらべてD-体の方が多くなる。これらのことから,シクロデキストリン残基とアミノ酸とが高分子膜中で相互作用し,とくにD-体との相互作用が強いため拡散性が抑制され,透過係数に差が生じたと考えられる。また,DL-アミノ酸を透過物質として光学分割を試みたところ,膜透過とまりL-体が濃縮きれ,フェニルアラニンの場合,その組成比はL/D=61.7/38.3となった。