- Development of a high throughput screening tool for biotransformations utilising a thermophilic l-aminoacylase enzyme
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Micro-reactors containing a monolith-immobilised thermophilic l-aminoacylase, from Thermococcus litoralis, have been developed for use in biotransformation reactions and a study has been carried out to investigate the stereospecificity and stability of the immobilised enzyme. The potential to use the developed micro-reactors as a tool for rapid screening of enzyme specificity was demonstrated, confirming that the l-aminoacylase showed a similar substrate specificity to that previously reported of the free enzyme. From this baseline, the technique was employed as a tool to evaluate potential unreported substrates with N-benzoyl- (l-threonine, l-leucine and l-arginine) and N-acetyl- (d,l-serine, d,l-leucine, l-tyrosine and l-lysine) protecting groups. The order of preferred substrates was found to be Phe > Thr > Leu > Arg for N-benzoyl substrates and Phe ? Ser > Leu > Met > Tyr > Trp for N-acetyl substrates. It was found that by using the micro-reactor a significantly smaller quantity of enzyme and substrates was required. It was shown that the micro-reactors were still operational in the presence of selected organic solvents, such as ethanol, methanol, acetone, dimethylformamide (DMF) and dimethylsulfoxide (DMSO). The results indicated that a combination of a small amount of an appropriate solvent (5% DMSO) and a higher reaction temperature could be employed in biotransformations where substrate solubility was an issue.
- Ngamsom,Hickey,Greenway,Littlechild,Watts,Wiles
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scheme or table
p. 81 - 86
(2010/10/21)
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- Efficient chemoenzymatic synthesis of enantiomerically pure α-amino acids
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A general two-step chemoenzymatic synthesis for enantiomerically pure natural and nonnatural α-amino acids is presented. In the first step of the sequence, the ubiquitous educts aldehyde, amide and carbon monoxide react by palladium-catalyzed amidocarbonylation to afford the racemic N-acyl amino acids in excellent yields. In the second step, enzymatic enantioselective hydrolysis yields the free optically pure a-amino acid and the other enantiomer as the N-acyl derivative, both in optical purities of 85-99.5% ee. The advantage of the chemoenzymatic process compared to other amino acid synthesis are demonstrated by the preparation of various functionalized (-OR, -Cl, -F, -SR) α-amino acids on a 10-g scale.
- Beller, Matthias,Eckert, Markus,Geissler, Holger,Napierski, Bernd,Rebenstock, Heinz-Peter,Holla, E. Wolfgang
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p. 935 - 941
(2007/10/03)
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- Enantioselective hydrolytic reactions of rice bran lipase (RBL): A first report
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Enantioselectivity has been observed in the hydrolysis of racemic N-acetyl amino acid esters with rice bran lipase (RBL). The enzyme shows selectivity towards the (S)-enantiomer. Products with high enantiomeric excess (e.e. >99%) are obtained depending upon the hydrophobicity of the amino acid as well as that of the leaving group.
- Fadnavis,Jadhav, Vasudev
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p. 2361 - 2366
(2007/10/03)
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- Selectivity in Carbonic Anhydrase Catalyzed Hydrolysis of Standard N-Acetyl-DL-amino Acid Methyl Esters
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Carbonic anhydrase-catalyzed hydrolysis of some standard N-acetyl-DL-amino acid methyl esters proceeds with high enantioselectivity.This enzyme hydrolyses selectively D amino acid derivatives in contrast to proteases which have a L stereoselectivity. Key Words: carbonic anhydrase, hydrolysis, N-acetyl-DL-amino acid methyl esters, enantioselectivity.
- Chenevert, Robert,Rhlid, Rachid Bel,Letourneau, Martin,Gagnon, Rene,D'Astous, Linda
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p. 1137 - 1140
(2007/10/02)
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- Catalysis by β-cyclodextrin in the reaction of p-nitrophenyl acetate with α-amino acids
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The reactions of p-nitrophenyl acetate, 1, with both enantiomers of the following α-amino acids: alanine (2a), methionine (2b), leucine (2c), and tryptophan (2d), were studied in the presence of β-cyclodextrin (β-CD).All the reactions were catalyzed by β-
- Barra, Monica,Rossi, Rita H. de
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p. 1124 - 1130
(2007/10/02)
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- Kinetic Resolution of Unnatural and Rarely Occuring Amino Acids: Enantioselective Hydrolysis of N-Acyl Amino Acids Catalyzed by Acylase I
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Acylase I (aminoacylase; N-acylamino-acid amidohydrolase, EC 3.5.1.14, from porcine kidney and the fungus Aspergillus) is broadly applicable enzymatic catalyst for the kinetic resolution of unnatural and rarely occuring α-amino acids.Its enantioselectivity for the hydrolysis of N-acyl L-α-amino acids is nearly absolute, yet it accepts substrates having a wide range of structure and functionality.This paper reports the initial rates of enzyme-catalyzed hydrolysis of over 50 N-acyl amino acids and analogues, the stabilities of the enzymes in aqueous and aqueous/organic solutions, and the effects of different acyl groups and metal ions on the rates of enzymatic hydrolysis.Eleven α-amino and α-methyl α-amino acids were resolved on a 2-29-g scale.Crude L- and D-amino acid products had generally >90percent ee.The utility of resolved amino acids as chiral synthons was illustrated by the preparation of (R)- and (S)-1-butene oxide and the diastereoselective (cis:trans, 7-8:1) iodolactonization of three 2-amino-4-alkenoic acid derivatives.
- Chenault, H. Keith,Dahmer, Juergen,Whitesides, George M.
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p. 6354 - 6364
(2007/10/02)
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- Efficient Asymmetric Hydrogenations of (Z)-2-Acetamidoacrylic Acid Derivatives with the Cationic Rhodium Complex of (2S,4S)-MOD-BPPM
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The preparation of (2S,4S)-MOD-BPPM ((2S,4S)-N-(t-butoxycarbonyl)-4-phosphino>-2-phosphino>methyl>pyrrolidine) and its application to highly effective asymmetric hydrogenations of (Z)-2-acetamidoacrylic acid derivatives are described.
- Takahashi, Hisashi,Achiwa, Kazuo
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p. 305 - 308
(2007/10/02)
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- O.N-Bis(diphenylphosphino) Derivatives of Chiral trans- and cis-2-Aminocyclohexanols: Synthesis and Enantioselective Behaviour as Ligands in Rh-based Homogeneous Hydrogenation Catalysts
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trans- and cis-2-Methylamino cyclohexanols (MAC) were prepared in enantiomerically pure forms and transformed into O.N-bis(diphenylphosphino) derivatives ("PONP").An analogous trans-1R;2R-aminocyclohexanol PONP could only be isolated in an impure form, whereas the attempted synthesis of PONP's of diastereomeric trans-2-(N-α-phenylethylamino)-cyclohexanols failed.Cationic Rh(I)-chelates of the new PONP's catalyzed the enantioselective hydrogenation of dehydro-α-acylamino acids with /= 97percent ee.A comparison of the enantiodiscriminating properties of the MAC-PONP's with structurally related chiral ligands leads to surprising conclusions.
- Pracejus, H.,Pracejus, G.,Costisella, B.
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p. 235 - 245
(2007/10/02)
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- Asymmetric Hydrogenation Catalyzed by Rhodium Complex with a New Chiral Bisphosphine Derived from L-Threonine
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A new chiral bisphosphine, (2R,3S)-1,2-bis(diphenylphosphino)-3-'Boc-aminobutane (RS-5), was prepared from L-threonine.Mesylation of 'Boc-L-threonine methyl ester (2) and subsequent reduction with sodium borohydride gave the alcohol (10), which was treated with potassium carbonate to afford a key intermediate, (2S,3S)-1-'Boc-3-methyl-2-aziridinemethanol (SS-7b).Mesylation of SS-7b, followed by treatment with sodium diphenylphosphide afforded the new chiral bisphosphine (RS-5).The structure of RS-5 was confirmed by the X-ray analysis of its crystalline CuCl complex (RS-12).The cationic rhodium (I) complexes prepared from RS-5 and RS-12 are efficient asymmetric hydrogenation catalysts for N-acyldehydroamino acids, giving (S))-N-acylamino acids in high optical yields (83-94percentee).
- Saito, Kunio,Saijo, Shigeyoshi,Kotera, Keishi,Date, Tadamasa
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p. 1342 - 1350
(2007/10/02)
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- ASYMMETRIC HYDROGENATION CATALYZED BY AMINOPHOSPHINE-PHOSPHINITERHODIUM COMPLEXES DERIVED FROM NATURAL AMINOALCOHOLS AND X-RAY CRYSTAL STRUCTURE OF (1,5-CYCLOOCTADIENE)-(S)-N-(DIPHENYLPHOSPHINO)-2-DIPHENYLPHOSPHINOXYMETHYLPYRROLIDINERHODIUM(I) PERCHLORATE
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From the cheap and readily available amino alcohols (S)-pyrrolidinemethanol ((S)-prolinol), and (S)-α-N-ethyl-aminobutanol, we have obtained two new aminophosphine-phosphinite ligands: (S)-N-(diphenylphosphino)-2-diphenylphosphinooxymethylpyrrolidine ((S)-Prolophos) and (S)-1-diphenylphosphinoxy-2-N-ethyl-N-diphenylphosphinoaminobutane ((S)-Butaphos).The rhodium(I) complexes of these phosphines act as efficient homogeneous hydrogenation catalysts at ambient temperature and pressures for dehydro N-acetyl amono acids, dehydro N-benzoyl amino acids and itaconic acid.An X-ray diffraction study of the complex *THF has been shown that the crystals belong to the monoclinic space group P21 with a 10.680(2), b 10.448(2), c 18.207(3) Angstroem and β 104.97(1)o.Refinements based on 2105 significant counter reflections led to a final R value of 0.060.The cation is in a distorted square planar geometry, the rhodium atom being bound to the two phosphorus atoms and to the two double bonds of the diene molecule.
- Cesarotti, E.,Chiesa, A.,Ciani, G.,Sironi, A.
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