Amino enantioselective membranes

A number of studies have recently been devoted to membrane applications [8, 100-102], Yoshikawa and co-workers developed an imprinting technique by casting membranes from a mixture of a Merrifield resin containing a grafted tetrapeptide and of linear co-polymers of acrylonitrile and styrene in the presence of amino acid derivatives as templates [103], The membranes were cast from a tetrahydrofuran (THF) solution and the template, usually N-protected d- or 1-tryptophan, removed by washing in more polar nonsolvents for the polymer (Fig. 6-17). Membrane applications using free amino acids revealed that only the imprinted membranes showed detectable permeation. Enantioselective electrodialysis with a maximum selectivity factor of ca. 7 could be reached, although this factor depended inversely on the flux rate [7]. Also, the transport mechanism in imprinted membranes is still poorly understood. 

Numerous other examples of enantioselective hydrolysis of esters have been reported. For example chymotrypsin, immobilised in a liquid membrane of kerosene or cydohexane, can be used for resolution of D,L-amino add esters in an emulsion type... 

Several hundred tons of L-methionine per year are produced by enzymatic conversion in an enzyme membrane reactor. An alternative approach is dynamic resolution, where the unconverted enantiomer is racemized in situ. Starting from racemic /V-acetyl-amino acid, the enantioselective L-acylase is used in combination with an TV-acyl-amino acid racemase to enable nearly total conversion of the substrate. 

It is significant that the reaction mixture was worked up by removal of the unreacted ester by hexane extraction and concentration of the aqueous layer to obtain the desired (i )-amino acid. The process has a high throughput and was easy to handle on a large scale. However, because of the nature of a batch process, the enzyme catalyst could not be effectively recovered, adding significantly to the cost of the product. In the further scale up to 100-kg quantity productions, the resolution process was performed using Sepracor s membrane bioreactor module. The enzyme was immobilized by entrapment into the interlayer of the hollow-fiber membrane. Water and the substrate amino ester as a neat oil or hexane solution were circulated on each side of the membrane. The ester was hydrolyzed enantioselectively by the enzyme at the membrane interface, and the chiral acid product... 

FIGURE 6.5 Membrane bioreactor for enzyme catalyzed enantioselective hydrolysis of racemic ethyl 2-amino-2-ethylhexanoate. 

R. Ueoka, Y. Matsumoto, R.A. Moss, S. Swarup, A. Sugii, K. Harada, J. Kikuchi, Y. Murakami, Membrane Matrix for the Hydrolysis of Amino Acid Esters with Marked Enantioselectivity , J. Am. Chem. Soc., 110,1588 (1988)... 

Bryjak, M., Kozlowski, J., Wieczorek, P., Kafarski, P. (1993). Enantioselective transport of amino acid through supported chiral liquid membranes. J. Membr. Sen, 85, 221-8. 

Shinbo, T., Yamaguchi, T., Yanagishita, H., Sakaki, K., Kitamoto, D., Sugiura, M. (1993). Supported liquid membranes for enantioselective transport of amino acid mediated by chiral crown ether—Effect of membrane solvent on transport rate and membrane stability. J. Membr. Sci., 84, 241-8. 

Maruyama A, Adachi N, Takatsuki T, Torii M, Sanui K, Ogata N. Enantioselective permeation of a-amino acid isomers through poly(amino acid)-derived membranes. Macromolecules 1990 23 2748-2752. 

Inoue K, Miyahara A, Itaya T. Enantioselective permeation of amino acids across membranes prepared from 3 -hclix bundle polyglutamates with oxy-ethylene chains. J Am Chem Soc 1997 119 6191-6192. 

A series of enantioselective imprinted polymer membranes for amino acid and peptide derivatives were prepared using oligopeptides as functional monomers [42-45]. A tetrahydrofuran solution containing a template molecule, a functional monomer of a peptide derivative attached on polystyrene resin that is commonly used in solid-phase peptide synthesis, copolymer of acrylonitrile and styrene, was poured into a flat laboratory dish and left for 24 h to remove the solvent. 

M. Yoshikawa, J. Izumi, T. Kitao, Enantioselective electrodialysis of amino acids with charged polar side chains through molecularly imprinted polymeric membranes containing DIDE derivatives, Polym. J., 1997, 29, 205. 

Another option for bond-forming reactions was mentioned by Degussa. It was considered to use known polymeric catalysts containing the amino acid proline [69] for enantioselective aldol or Mannich reactions in membrane reactors [70]. Concrete examples were unfortunately not published. 

Enantioselective transport of several amino-acids through a polymer-supported liquid membrane containing the chiral crown ether (83) has been reported. The best result was observed with the racemic mixture of phenylglycine the D-enantiomer was transported 22.7 times faster than the L-enantiomer <85CL1549>. 

Preparation and characterization of liposomes formed with natural phospholipids were well established. However, in using liposomes for simulation of enzymatic functions, especially in acid-base catalysis, difficulties would be encountered due to their chemicai and morphological instabilities. Thus, bilayer membranes composed of synthetic amphiphiles are more favorable candidates for enzyme mimics. For example, artificial vitamin Bg-dependent enzymes were constructed from catalytic bilayer membranes in combination with a bilayer-forming peptide lipid (10), a hydrophobic vitamin derivative (11), and metal ions (Fig. 5). The catalyst acts as an artificial aminotransferase, showing marked substrate specificity, high enantioselectivity, and turnover behavior for the transamination of a-amino acid with a-keto acids. In addition, the reaction fields provided by the catalytic bilayer membranes are suitable to establish multienzyme systems through functional ahgnments of artificial enzymes and natural ones in a sequential manner. 

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