- Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
-
Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.
- Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
-
supporting information
p. 390 - 398
(2021/01/13)
-
- Ultrasound-Controlled Chiral Separation of Four Amino Acids and 2,2,2-Trifluoro-1-(9-anthryl)ethanol
-
Chiral separation of 4-hydroxyphenylglycine, phenylglycine, tryptophan, methionine, and 2,2,2-trifluoro-1-(9-anthryl)ethanol (TFAE) was performed under ultrasound reduction at room temperature and high temperature (50 °C). At high temperature (50 °C), both α and Rs were improved slightly under ultrasound reduction as compared to those under non-ultrasonic and ultrasonic irradiation (50 watt/L) conditions. Even at low temperatures, the largest α was observed under ultrasound reduction conditions, except in the case of methionine. However, at low temperature, Rs was reduced under ultrasound (50 watt/L) irradiation, but was improved under ultrasound reduction rather than under the continuous ultrasonic irradiation. Similar to the fact that gradient elution (based on solvent polarity) can improve α, ultrasound reduction can improve α and Rs. Ultrasound reduction is demonstrated to aid the rapid separation of chiral compounds with improved resolution, especially, at high temperatures. Although chromatographic separation using ultrasound has been rarely dealt with until now, ultrasound can be used as an external field in chromatography.
- Lee, Jae Hwan,Ryoo, Jae Jeong
-
p. 146 - 149
(2019/02/07)
-
- Light-Driven Kinetic Resolution of α-Functionalized Carboxylic Acids Enabled by an Engineered Fatty Acid Photodecarboxylase
-
Chiral α-functionalized carboxylic acids are valuable precursors for a variety of medicines and natural products. Herein, we described an engineered fatty acid photodecarboxylase (CvFAP)-catalyzed kinetic resolution of α-amino acids and α-hydroxy acids, which provides the unreacted R-configured substrates with high yields and excellent stereoselectivity (ee up to 99 %). This efficient light-driven process requires neither NADPH recycling nor prior preparation of esters, which were required in previous biocatalytic approaches. The structure-guided engineering strategy is based on the scanning of large amino acids at hotspots to narrow the substrate binding tunnel. To the best of our knowledge, this is the first example of asymmetric catalysis by an engineered CvFAP.
- Xu, Jian,Hu, Yujing,Fan, Jiajie,Arkin, Mamatjan,Li, Danyang,Peng, Yongzhen,Xu, Weihua,Lin, Xianfu,Wu, Qi
-
supporting information
p. 8474 - 8478
(2019/05/24)
-
- Deracemization and Stereoinversion of α-Amino Acids by l-Amino Acid Deaminase
-
Enantiomerically pure α-amino acids are compounds of primary interest for the fine chemical, pharmaceutical, and agrochemical sectors. Amino acid oxidases are used for resolving d,l-amino acids in biocatalysis. We recently demonstrated that l-amino acid deaminase from Proteus myxofaciens (PmaLAAD) shows peculiar features for biotechnological applications, such as a high production level as soluble protein in Escherichia coli and a stable binding with the flavin cofactor. Since l-amino acid deaminases are membrane-bound enzymes, previous applications were mainly based on the use of cell-based methods. Now, taking advantage of the broad substrate specificity of PmaLAAD, a number of natural and synthetic l-amino acids were fully converted by the purified enzyme into the corresponding α-keto acids: the fastest conversion was obtained for 4-nitrophenylalanine. Analogously, starting from racemic solutions, the full resolution (ee >99%) was also achieved. Notably, d,l-1-naphthylalanine was resolved either into the d- or the l-enantiomer by using PmaLAAD or the d-amino acid oxidase variant having a glycine at position 213, respectively, and was fully deracemized when the two enzymes were used jointly. Moreover, the complete stereoinversion of l-4-nitrophenylalanine was achieved using PmaLAAD and a small molar excess of borane tert-butylamine complex. Taken together, recombinant PmaLAAD represents an l-specific amino acid deaminase suitable for producing the pure enantiomers of several natural and synthetic amino acids or the corresponding keto acids, compounds of biotechnological or pharmaceutical relevance. (Figure presented.).
- Rosini, Elena,Melis, Roberta,Molla, Gianluca,Tessaro, Davide,Pollegioni, Loredano
-
p. 3773 - 3781
(2017/11/13)
-
- Chromatographic Resolution of α-Amino Acids by (R)-(3,3'-Halogen Substituted-1,1'-binaphthyl)-20-crown-6 Stationary Phase in HPLC
-
Three new chiral stationary phases (CSPs) for high-performance liquid chromatography were prepared from R-(3,3'-halogen substituted-1,1'-binaphthyl)-20-crown-6 (halogen = Cl, Br and I). The experimental results showed that R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 (CSP-1) possesses more prominent enantioselectivity than the two other halogen-substituted crown ether derivatives. All twenty-one α-amino acids have different degrees of separation on R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6-based CSP-1 at room temperature. The enantioselectivity of CSP-1 is also better than those of some commercial R-(1,1'-binaphthyl)-20-crown-6 derivatives. Both the separation factors (α) and the resolution (Rs) are better than those of commercial crown ether-based CSPs [CROWNPAK CR(+) from Daicel] under the same conditions for asparagine, threonine, proline, arginine, serine, histidine and valine, which cannot be separated by commercial CR(+). This study proves the commercial usefulness of the R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 chiral stationary phase.
- Wu, Peng,Wu, Yuping,Zhang, Junhui,Lu, Zhenyu,Zhang, Mei,Chen, Xuexian,Yuan, Liming
-
p. 1037 - 1042
(2017/07/25)
-
- t-BUTYLKETONE BINAPHTHOL DERIVATIVES AND PREPARING METHOD THEREOF
-
The present disclosure relates to a t-butylketone binaphthol derivative and a method of preparing the same, the t-butylketone binaphthol derivative being a high-efficiency chiral extracting agent which has a very high chiral selectivity enabling to extract an amino acid from an aqueous solution phase to an organic layer and to facilitate its hydrolysis, and enabling a continuous reuse of the organic layer.
- -
-
Paragraph 0097
(2017/01/17)
-
- SEPARATING AGENT AND MANUFACTURING METHOD THEREOF
-
An embodiment of the present invention is a separating agent wherein a group represented by a chemical formula of: or a group represented by a chemical formula of: is introduced on a surface thereof.
- -
-
Paragraph 0067; 0068; 0069; 0070; 0071; 0072; 0097; 0098
(2015/01/07)
-
- Chemical approach for interconversion of (S)- and (R)-α-amino acids
-
Here we report a general method for the preparation of unnatural (R)-α-amino acids via complexation of α-(phenyl)ethylamine derived chiral reagent (S)-3 with various (S)-α-amino acids. The reactions proceed with synthetically useful chemical yields and thermodynamically controlled diastereoselectivity. Chiral reagent (S)-3 can be conveniently recovered and reused without any loss of enantiomeric purity and reactivity. The Royal Society of Chemistry 2013.
- Sorochinsky, Alexander E.,Ueki, Hisanori,Ace?a, José Luis,Ellis, Trevor K.,Moriwaki, Hiroki,Sato, Tatsunori,Soloshonok, Vadim A.
-
p. 4503 - 4507
(2013/08/23)
-
- SEPARATING AGENT FOR CHROMATOGRAPHY
-
A separating agent for chromatography is provided that is useful for the separation of specific compounds, e.g., for the optical resolution of amino acids. This separating agent for chromatography provides a higher productivity and contains a crown ether-like cyclic structure and optically active binaphthyl. This separating agent for chromatography containing a crown ether-like cyclic structure and optically active binaphthyl is provided by introducing a substitution group for binding to carrier into a specific commercially available 1,1′-binaphthyl derivative that has substituents at the 2, 2′, 3, and 3′ positions, then introducing a crown ether-like cyclic structure, and subsequently chemically bonding the binaphthyl derivative to the carrier through the substitution group for binding to carrier.
- -
-
Paragraph 0074; 0075
(2013/08/15)
-
- Increasing the storage and oxidation stabilities of N-acyl-d-amino acid amidohydrolase by site-directed mutagenesis of critical methionine residues
-
The recombinant N-acyl-d-amino acid amidohydrolase (N-d-AAase) of Variovorax paradoxus Iso1 was unstable during protein purification and storage at 4 °C. Since the methionine oxidation might be the artificial factor leading to the inactivation of N-d-AAase, eight potential oxidation sensitive methionine residues of the enzyme were individually substituted with leucine utilizing site-directed mutagenesis. Among them, five mutants, M39L, M56L, M221L, M254L, and M352L remained at least 70% of wild-type specific activity. The enzyme kinetic parameters of M221L revealed a 44% decrease in Km, and finally reflected a 2.4-fold increase in kcat/Km. Moreover, its half-life at 4 °C increased up to 6-fold longer than that of the wild-type. Structural analysis of each methionine substitution was carried out based on the crystal structure of N-d-AAase from Alcaligenes faecalis DA1. Met221 spatial closeness to the zinc-assistant catalytic center is highly potential as the primary site for oxidative inactivation. We conclude that the replacement of methionine M221 with leucine in N-d-AAase successfully enhances the oxidative resistance, half-life, and enzyme activity. This finding provides a promising basis for the engineering the stability and activity of N-d-AAase.
- Peng, I-Chen,Lo, Kai-Yin,Hsu, Chun-Hua,Lee, Chia-Yin
-
p. 1785 - 1790
(2013/03/13)
-
- An improved racemase/acylase biotransformation for the preparation of enantiomerically pure amino acids
-
Using directed evolution, a variant N-acetyl amino acid racemase (NAAAR G291D/F323Y) has been developed with up to 6-fold higher activity than the wild-type on a range of N-acetylated amino acids. The variant has been coupled with an enantiospecific acylase to give a preparative scale dynamic kinetic resolution which allows 98% conversion of N-acetyl-dl-allylglycine into d-allylglycine in 18 h at high substrate concentrations (50 g L-1). This is the first example of NAAAR operating under conditions which would allow it to be successfully used on an industrial scale for the production of enantiomerically pure α-amino acids. X-ray crystal analysis of the improved NAAAR variant allowed a comparison with the wild-type enzyme. We postulate that a network of novel interactions that result from the introduction of the two side chains is the source of improved catalytic performance.
- Baxter, Scott,Royer, Sylvain,Grogan, Gideon,Brown, Fraser,Holt-Tiffin, Karen E.,Taylor, Ian N.,Fotheringham, Ian G.,Campopiano, Dominic J.
-
supporting information
p. 19310 - 19313
(2013/02/23)
-
- Chiral separation of underivatized amino acids by reactive extraction with palladium-BINAP complexes
-
(Figure Presented) In answer to the need for a more economic technology for the separation of racemates, a novel system for reactive enantioselective liquid-liquid extraction (ELLE) is introduced. Palladium (S)-BINAP complexes are employed as hosts in the separation of underivatized amino acids. The system shows the highest selectivity for the ELLE of tryptophan with metal complexes as hosts reported to date and shows a good selectivity toward a range of natural and unnatural amino acids. Furthermore, the host can be prepared in situ from commerically available compounds. Bulk-membrane transport in the form of U-tube experiments demonstrates the enantioselective and catalytic nature of the transport. The dependency of the system on parameters such as pH, organic solvent, and host-substrate ratio has been established. 31P NMR spectroscopy has been used to confirm the preferred enantiomer in the extraction experiments. The intrinsic selectivity was deduced by determination of the association constants of the palladium complex with the tryptophan enantiomers.
- Verkuijl, Bastiaan J. V.,Minnaard, Adriaan J.,De Vries, Johannes G.,Feringa, Ben L.
-
experimental part
p. 6526 - 6533
(2010/03/01)
-
- Dynamic Kinetic resolution of α-amino acid esters in the presence of aldehydes
-
A convenient procedure for the racemization of α-amino acid esters in the presence of catalytic amounts of salicylaldehydes is described. The combination of this racemization protocol with lipase-catalyzed ester hydrolysis allows successful dynamic kinetic resolution of various α-amino acid esters. The corresponding α-amino acids are obtained in high yield and optical purity. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Schichl, Daniel A.,Enthaler, Stephan,Holla, Wolfgang,Riermeier, Thomas,Kragl, Udo,Beller, Matthias
-
scheme or table
p. 3506 - 3512
(2009/04/07)
-
- Using ionic liquid [EMIM][CH3COO] as an enzyme-'friendly' co-solvent for resolution of amino acids
-
An ionic liquid (IL), 1-ethyl-3-methylimidazolium acetate [EMIM][CH3COO], was used in 0-4.0 M (~60% IL, v/v), as a nonvolatile organic medium for the enzymatic resolution of amino acids. When dl-phenylalanine methyl ester was studied as a model substrate, high enantiomeric excesses (ee) of l-amino acid were obtained in all ionic concentrations; however, lower yields were observed at high IL concentrations. This IL is more enzyme-'friendly' than the hydrophilic organic solvent acetonitrile and those ILs containing chaotropic anions (such as [EMIM][OTs]). Among three proteases and two lipases investigated, lyophilized Bacillus licheniformis protease exhibited the best enantioselectivity and activity. Highly enantioselective resolutions were also produced for several other amino acids in 2.0 M IL. Interestingly, high ee were also found in deuterium oxide (D2O) rather than in ordinary water, and a further enhancement was achieved with the co-existence of [EMIM][CH3COO]. The heavy water effect was explained in terms of protein stabilization by D2O. The secondary structural changes of enzyme in various media were interpreted by the second derivatives of FT-IR spectra.
- Zhao, Hua,Jackson, Lee,Song, Zhiyan,Olubajo, Olarongbe
-
p. 2491 - 2498
(2007/10/03)
-
- Creation of a broad-range and highly stereoselective D-amino acid dehydrogenase for the one-step synthesis of D-amino acids
-
Using both rational and random mutagenesis, we have created the first known broad substrate range, nicotinamide cofactor dependent, and highly stereoselective D-amino acid dehydrogenase. This new enzyme is capable of producing D-amino acids via the reductive amination of the corresponding 2-keto acid with ammonia. This biocatalyst was the result of three rounds of mutagenesis and screening performed on the enzyme meso-diaminopimelate D-dehydrogenase. The first round targeted the active site of the wild-type enzyme and produced mutants that were no longer strictly dependent on the native substrate. The second and third rounds produced mutants that had an increased substrate range including straight-and branched-aliphatic amino acids and aromatic amino acids. The very high selectivity toward the D-enantiomer (95 to >99% ee) was shown to be preserved even after the addition of the five mutations found in the three rounds of mutagenesis and screening. This new enzyme could complement and improve upon current methods for D-amino acid synthesis.
- Vedha-Peters, Kavitha,Gunawardana, Manjula,Rozzell, J. David,Novick, Scott J.
-
p. 10923 - 10929
(2007/10/03)
-
- Analysis of underivatized amino acids and their D/L-enantiomers by sheathless capillary electrophoresis/electrospray ionization-mass spectrometry
-
Capillary electrophoresis/electrospray ionization-mass spectrometry (CE/ESI-MS) was applied to the analysis of underivatized amino acids and the separation of their D/L-enantiomers. Under full-scan mode, all standard protein amino acids were separated and detected at low-femtomole levels using a 130-cm-long, 20-μm-i.d., 150-μm-o.d. underivatized fused-silica capillary with 1 M formic acid as the background electrolyte. The CE/ESI-MS technique was also applied to the separation of L-arginine from L-canavanine (a close analogue of arginine where the terminal methylene linked to the guanidine group of arginine is replaced by an oxygen atom) in a complex mixture containing all standard protein amino acids. The utility of CE/ESI-MS in the analysis of real-world samples was demonstrated by the identification of two metabolic diseases (PKU and tyrosinemia) through blood analysis with minimal sample preparation. In addition, the on-line separation of 11 underivatized L-amino acids from their D-enantiomers was achieved by using a 30 mM solution of (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as the background electrolyte.
- Schultz, Casey L.,Moini, Mehdi
-
p. 1508 - 1513
(2007/10/03)
-
- Amine-boranes: Effective reducing agents for the deracemisation of DL-amino acids using L-amino acid oxidase from Proteus myxofaciens
-
The deracemisation of DL-α-amino acids using L-amino acid oxidase from Proteus myxofaciens and amine-boranes as chemical reducing agents has been investigated. Amine-boranes were found to be of particular interest in terms of reactivity and chemoselectivity compared to sodium borohydride and cyanoborohydride. Starting from the racemate, a range of D-amino acids were obtained in yields of up to 90% and e.e. >99%.
- Alexandre, Fran?ois-René,Pantaleone, David P.,Taylor, Paul P.,Fotheringham, Ian G.,Ager, David J.,Turner, Nicholas J.
-
p. 707 - 710
(2007/10/03)
-
- Retention and selectivity of teicoplanin stationary phases after copper complexation and isotopic exchange
-
Teicoplanin is a macrocyclic glycopeptide that is highly effective as a chiral selector for LC enantiomeric separations. Two possible interaction paths were investigated and related to solute retention and selectivity: (1) interactions with the only teicoplanin amine group and (2) role of hydrogen bonding interactions. Mobile phases containing 0.5 and 5 mM copper ions were used to try to block the amine group. In the presence of copper ions, it was found that the teicoplanin stationary phase has a decreased ability to separate most underivatized racemic amino acids. However, it maintained its ability to separate enantiomers that were not α - amino acids. It is established that there is little copper - teicoplanin complex formation. The effect of Cu2+ on the enantioseparation of some α - amino acids appears to be due to the fact that these solutes are good bidentate ligands and form complexes with copper ions in the mobile phase. Isotopic exchange with deuterium oxide was performed using acetonitrile - heavy water mobile phases. It was found that the retention times of all amino acids were lower with deuterated mobile phases. The retention times of polar or apolar molecules without amine groups were higher with deuterated mobiles phases. In all cases, the enantio-selectivity factors were unaffected by the deuterium exchange. It is proposed that the electrostatic interactions are decreased in the deuterated mobile phases and the solute-accessible stationary-phase volume is somewhat swollen by deuterium oxide. The balance of these effects is a decrease in the amino acid retention times and an increase in the apolar solute retention time. The enantio-selectivity factors of all of the molecules remain unchanged because all of the interactions are changed equally. We propose a new global quality criterion (the E factor) for comparing and evaluating enantiomeric separations.
- Berthod,Valleix,Tizon,Leonce,Caussignac,Armstrong
-
p. 5499 - 5508
(2007/10/03)
-
- Compounds for and methods of inhibiting matrix metalloproteinases
-
The present invention relates to compounds of Formula I that inhibit matrix metalloproteinases and to a method of inhibiting matrix metalloproteinases using the compounds More particularly, the present invention relates to a method of treating diseases in which matrix metalloproteinases are involved such as multiple sclerosis, atherosclerotic plaque rupture, restenosis, aortic aneurysm, heart failure, periodontal disease, corneal ulceration, burns, decubital ulcers, chronic ulcers or wounds, cancer metastasis, tumor angiogenesis, osteoporosis, rheumatoid or osteoarthritis, renal disease, left ventricular dilatation, or other autoimmune or inflammatory diseases dependent upon tissue invasion by leukocytes.
- -
-
-
- New hydantoinases from thermophilic microorganisms - Synthesis of enantiomerically pure D-amino acids
-
A series of 14 D-α-amino acids were prepared in high chemical and optical yields from the corresponding racemic hydantoins by employing two novel hydantoinases from thermophilic microorganisms.
- Keil,Schneider,Rasor
-
p. 1257 - 1260
(2007/10/02)
-
- Structural identification of the degradation products of the antitumor peptide antagonist [Arg6, D-Trp7,9, MePhe8]substance P (6-11)
-
The basic hexapeptide antagonist [Arg6, D-Trp7,9, MePhe8]substance P (6-11) was degraded in acid and alkaline media. In acid solution, only one degradation product is found whereas in alkaline solution at least six products are formed. These compounds were analytically characterized and structurally identified by reversed-phase high-performance liquid chromatography, capillary electrophoresis, liquid chromatography/mass spectrometry, fast atom bombardment tandem mass spectrometry, optical rotation analysis, and chiral gas chromatography. The product formed in acidic solution is the terminally deamidated antagonist [Arg6, D-Trp7,9, MePhe8]substance P (6-11); this product was also found in alkaline degradation mixtures. Other important degradation products originate from racemization of the amino acid residue L-Met, formation of ornithine from Arg, and the oxidation of Met to its sulfoxide form.
- Reubsaet,Beijnen,Bult,Hop,Vermaas,Kellekule,Kettenes-Van Den Bosch,Underberg
-
p. 4431 - 4436
(2007/10/02)
-
- Characterization of D-aminoacylase from Alcaligenes denitrificans DA181.
-
The D-aminoacylase produced by Alcaligenes denitrificans DA181 was a new type of aminoacylase which had both high stereospecificity and specific activity. The molecular weight and isoelectric point of this enzyme were 58,000 and 4.4, respectively. The apparent Km and kcat values of this enzyme for N-acetyl-D-methionine were estimated to be 0.48 mM and 6.24 x 10(4) min-1, respectively. The optimum temperature was 45 degrees C. The enzyme was stable up to 55 degrees C for 1 hr in the presence of 0.2 mg/ml bovine serum albumin. The enzyme was stable in the pH range of 6.0 to 11.0 with an optimum pH of 7.5. This enzyme contained about 2.1 g atom of zinc per mole of enzyme. Enzyme activity was inhibited by incubation with EDTA. The inhibition by EDTA was fully reversed by Co2+ and partially by Zn2+.
- Yang,Hsiao,Li,Yano,Tsugita,Tsai
-
p. 1392 - 1395
(2007/10/02)
-
- Plasmid-based, D-aminopeptidase-catalysed synthesis of (R)-amino acids
-
The gene for D-aminopeptidase from Ochrobactrum anthropi SCRC Cl-38 was cloned in Eschericha coli JM 109.An expression plasmid pCl138DP (4.5 kb) was constructed.The amount of the enzyme in a cell-free extract of E. coli JM109/pCl138DP was elevated up to 288000 units/liter culture, which is about 3600-fold over that of O.anthropi SCRC Cl-38.It was calculated that the enzyme comprised about 30percent of the total extractable cellular protein.The intact cells of the E.coli transformant were used as a catalyst for (R)-stereospecific hydrolysis of several racemic amino amides HCl.Complete hydrolysis of (R)-alanine amide was achieved in a short time (4 1/2 h) from 5.0M racemic alanine amide HCl using cells of the E.coli transformant.The concentration of (R)-alanine reached 220 g/l.The cells or the cell-free extract catalyzed the synthesis of (R)-2-aminobutyric acid, (R)-methionine, (R)-norvaline and (R)-norleucine from their amides in a similar manner.
- Asano, Yasuhisa,Kishino, Katsuhiko,Yamada, Akiko,Hanamoto, Sawako,Kondo, Kiyosi
-
p. 206 - 208
(2007/10/02)
-
- Method of making a diastereomeric mixture containing two diastereomeric N-acyl-amino acid esters
-
In the process of hydrocarboxylating an α-enamide with CO and an organic hydroxyl compound to produce a N-acyl-α-amino acid ester, the improvement comprising using as the organic hydroxyl compound reactant, an organic hydroxyl compound which has a chiral center that is essentially all L or D, thereby producing a reaction mixture having essentially no enantiomeric pairs and containing diastereomeric N-acyl-α-amino acid esters having two chiral centers.
- -
-
-
- Effect of the Side Chain on the Racemization of Amino Acids in Aqueous Solution
-
The rate of racemization of 13 amino acids possessing hydroxy, carboxy, alkoxy, carboalkoxy, alkyl, aryl, and thioether side chains were compared.Reaction conditions were identical for all amino acids studied.Gas chromatography was used to determine the percent of D isomer present.Hydroxy amino acids racemized most rapidly, but conversion to an ether function reduced the rate considerably.The increased racemization rate of methionine (R = CH2CH2SCH3) over Ala (R = CH3) has been attributed to orbital overlap from the sulfur.Asp racemized faster than Glu, α-aminoadipic acid, and pyroglutamic acid. β- and γ-monomethyl esters of aspartic and glutamic acids, respectively, racemized only slightly faster than the corresponding free acids.The slight increase in rate appears attributable to a solvent change brought on by ester hydrolysis.Under the reaction conditions, pH 8 and 140 deg C, hydrolysis of the esters competed favorably with racemization at the methine carbon.The relatively lower racemization rate observed in the case of Glu compared with Asp resulted from the slow formation of pyroglutamic acid.Pyroglutamic acid racemized at a considerably slower rate than acidic amino acids.The differences in the racemization rates with changes in the R group are discussed in terms of several factors, including intramolecular reactions, direct field effects, orbital overlap, and solvation effects, as well as inductive, resonance, and steric factors.
- Smith, Grant Gill,Reddy, G. Vanita
-
p. 4529 - 4535
(2007/10/02)
-
- Method of making a diastereomeric mixture containing two diastereomeric N-acyl-amino acid esters
-
In the process of hydrocarboxylating an α-enamide with CO and an organic hydroxyl compound to produce a N-acyl-α-amino acid ester, the improvement comprising using as the organic hydroxyl compound reactant, an organic hydroxyl compound which has a chiral center that is essentially all L or D, thereby producing a reaction mixture having essentially no enantiomeric pairs and containing diastereomeric N-acyl-α-amino acid esters having two chiral centers.
- -
-
-
- Mechanism of Asymmetric Production of D-Amino Acids from the Corresponding Hydantoins by Pseudomonas sp.
-
The mechanism of asymmetric production of D-amino acids from the corresponding hydantoins by Pseudomonas sp.AJ-11220 was examined by investigating the properties of the enzymes involved in the hydrolysis of DL-5-substituted hydantoins.The enzymatic production of D-amino acids from the corresponding hydantoins by Pseudomonas sp.AJ-11220 involved the following two successive reactions; the D-isomer specific hydrolysis, i.e., the ring opening of D-5-substituted hydantoins to D-form N-carbamyl amino acids by an enzyme, D-hydantoin hydrolase (D-HYD hydrolase), followed by the D-isomer specific hydrolysis, i.e., the cleavage of N-carbamyl-D-amino acids to D-amino acids by an enzyme, N-carbamyl-D-amino acid hydrolase (D-NCA hydrolase).L-5-Substituted hydantoins not hydrolyzed by D-HYD hydrolase were converted to D-form 5-substituted hydantoins through spontaneous racemization under the enzymatic reaction conditions.It was proposed that almost all of the DL-5-substituted hydantoins were stoichiometrically and directly converted to the corresponding D-amino acids through the successive reactions of D-HYD hydrolase and D-NCA hydrolase in parallel with the spontaneous racemization of L-5-substituted hydantoins to those of DL-form.
- Yokozeki, Kenzo,Kubota, Koji
-
p. 721 - 728
(2007/10/02)
-
- Optimal Conditions for the Enzymatic Production of D-Amino Acids from the Corresponding 5-Substituted Hydantoins
-
The reaction conditions for the production of D-p-hydroxyphenylglycine (D-HPG) from DL-5-(p-hydroxyphenyl)hydantoin (DL-HPH) by cells of Pseudomonas sp.AJ-11220 and the cultural conditions for this bacterium for the formation of the D-HPG-producing enzyme involved by this bacterium were investigated.The optimal pH of this reaction was about 8.0 and the optimal temperature about 43 deg C.The D-HPG producing enzyme was inducibly produced in Pseudomonas sp.AJ-11220 in proportion to the cell growth.Cells containing high activity were obtained when Pseudomonas sp.AJ-11220 was grown in a medium containing 20 g of glucose 5 g of (NH4)2SO4, 1g of KH2PO4, 3 g of K2HPO4, 0.5 g of MgSO4.7H2O, 0.01 g of FeSO4.7H2O, 0.01 g of MnSO4.4H2O, 10 g of yeast extract 5 g of DL-5-cyanoethylhydantoin and 20 g of CaCO3 in a total volume of 1 liter (pH 7.0).Under the optimal conditions, 25 mg/ml of D-HPG was asymmetrically and directly produced from 30 mg/ml of DL-HPH with a molar yield of 92percent.Various D-amino acids could also be effectively produced from the corresponding 5-substituted hydantoins.
- Yokozeki, Kenzo,Nakamori, Shigeru,Yamanaka, Shigeru,Eguchi, Chikahiko,Mitsugi, Koji,Yoshinaga, Fumihiro
-
p. 715 - 720
(2007/10/02)
-
- PALLADIUM-CATALYZED REACTION OF ALLYL CARBAMATES; ALLYLATION OF CARBONUCLEOPHILES, AND PROTECTION-DEPROTECTION OF AMINES
-
Allylation of carbonucleophiles with allylic carbamates under neutral conditions has been studied.The C-allylation of carbonucleophile is competitive with the N-allylation of amines, and the structure of amines is crucial for the selectivity.Bulky secondary amines gave the best results.Also a new method of protection-deprotection of amines as carbamates has been developed.Smooth deprotection is possible by the palladium-catalyzed reaction of allyl carbamates with formic acid.This method is particulary useful for primary amines, including optically active amino acids.
- Minami, Ichiro,Ohashi, Yukihiro,Shimizu, Isao,Tsuji, Jiro
-
p. 2449 - 2452
(2007/10/02)
-
- Homocysteine Transmethylation in Methanol-utilizing Bacteria and Its Application to L-Methionine Production
-
Resting cells of ribulose monophosphate pathway (RMP)-type methylotroph strain OM33 and serine pathway-type methylotroph Pseudomonas FM518 actively catalyzed the formation of L-methionine from DL-homocysteine and methanol.Cyanocobalamin stimulated the L-methionine formation by strain OM33, indicating that vitamin B12 dependent homocysteine transmethylase functions in this obligate methylotroph.Whereas, the L-methionine formation by Pseudomonas FM518 was not stimulated by added cyanocobalamin because this strain is a vitamin B12-producer.The Pseudomonas FM518 cells formed L-methionine with betaine or L-serine as well as methanol as the methyl donor source.The conditions for the formation of L-methionine from DL-homocysteine and methanol were investigated preliminarily using the reaction system with resting cells of an ethionine-resistant mutant of Pseudomonas FM518.The methanol-grown cells at the exponential phase of growth possessed the highest activity.Under the optimum reaction conditions, 2.6 mM L-methionine was formed from 30 mM DL-homocysteine and 0.8 M methanol.
- Morinaga, Yasushi,Tani, Yoshiki,Yamada, Hideaki
-
p. 143 - 148
(2007/10/02)
-
- Obtention d'amino acides optiquement actifs a l'aide d'hydantoinases
-
5-substituted hydantoines are intermediates in the Bucherer synthesis, the most widely used chemical synthesis of α-aminoacids.Enzymatic hydrolysis of these intermediates with hydantoinases leads to asymetric synthesis of optically active aminoacids.The enzymatic activities of two microbial strains are described: a Pseudomonas Sp. and an Arthrobacter globiformis, which catalyze the hydrolysis of a wide variety of hydantoines into D and L α-aminoacids respectively.In both cases, it was noticed that α-ureido (or 2-carbamoyl acids) are the reactive intermediates.Evidence is provided for the existence of a racemase.The experimental conditions for the culture of Arthrobacter are briefly described.
- Guivarch, Marcel,Gillonnier, Claude,Brunie, Jean-Claude
-
-