- A Facile Method for the Production of D-p-Hydroxyphenylglycine. Asymmetric Transformation of DL-p-Hydroxyphenylglycine Using (+)-1-Phenylethanesulfonic Acid
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A practical method for the production of D-p-hydroxyphenylglycine, useful as a starting material for preparing semisynthetic penicillins or cephalosporins, has been developed.The diastereomeric salts of DL-p-hydroxyphenylglycine with (+)-1-phenylethanesulfonic acid as a resolving agent, were efficiently resolved into less soluble D-p-hydroxyphenylglycine (+)-1-phenylethanesulfonate and soluble L-HPG * (+)-PES by the fractional crystallization of its salts in aqueous solution.The soluble L-HPG * (+)-PES could be easily epimerized into DL-HPG * (+)-PES by heating it with water containing a 0.1 molar equivalent of free DL-HPG in an autoclave.When the fractional crystallization of DL-HPG with (+)-PES was simultaneously carried out under the epimerizing conditions, the DL-HPG * (+)-PES was transformed into D-HPG * (+)-PES in up to 90percent yield.The present asymmetric transformation should be a suitable method for preparing D-HPG in a large scale.
- Yoshioka, Ryuzo,Tohyama, Masanori,Yamada, Shigeki,Ohtsuki, Osamu,Chibata, Ichiro
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- Crystallization induced asymmetric transformation: Synthesis of D-p-hydroxyphenylglycine
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D-p-hydroxyphenylglycine (D-HPG) is prepared from racemic HPG via salicylaldehyde mediated resolution-racemization of the corresponding D-3-bromocamphor-8-sulfonate salt in acetic acid. After slurry purification to improve the de to > 99.9%, the crystallized salt is neutralized to produce D-HPG in 92% overall yield and 99.9% ee.
- Bhattacharya,Araullo-Mcadams,Meier
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Read Online
- The Optical Resolution and Asymmetric Transformation of DL-p-Hydroxyphenylglycine with (+)-1-Phenylethanesulfonic Acid
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Optically active 1-phenylethanesulfonic acid was found to be an efficient resolving agent for the optical resolution and asymmetric transformation of DL-p-hydroxyphenylglycine.When DL-p-hydroxyphenylglycine was resolved by the fractional crystallization of its diastereomeric salt with (+)-1-phenylethanesulfonic acid, less soluble D-p-hydroxyphenylglycine (+)-1-phenylethanesulfonate was obtained in a good yield.Soluble L-HPG*(+)-PES was easily epimerized into DL-HPG*(+)-PES by heating it at 100 deg C in glacial acetic acid in the presence of a small amount of salicylaldehyde.Under such epimerizing conditions, the asymmetric transformation of DL-HPG*(+)-PES was attempted by simultaneously combining the fractional crystallization of the less soluble D-HPG*(+)-PES and the epimerization of the soluble L-HPG*(+)-PES.This asymmetric tranformation was achieved succesfully; that is, 80percent of the DL-HPG used as the starting material was converted into D-HPG.
- Yoshioka, Ryuzo,Tohyama, Masanori,Ohtsuki, Osamu,Yamada, Shigeki,Chibata, Ichiro
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- D-2-AMINO-2-(4-HYDROXYPHENYL)ACETAMIDO.
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The 4 -methyoxybenzyloxycarbonyl group of 7- left bracket D-2-(4-hydroxyphenyl)-2-(4-methoxybenzyloxycarbonylamino)acetamido right bracket cephalosporanic acid was effectively removed with p-toluenesulfonic acid in acetonitrile. The mechanism of the deprotection is discussed and the role of acetonitrile can reasonably be explained in terms of the Ritter reaction.
- Yamada,Tobiki,Tanno,Suzuki,Jimpo,Ueda,Nakagome
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- RETRACTED ARTICLE: Chemoenzymatic Method for Enantioselective Synthesis of (R)-2-Phenylglycine and (R)-2-Phenylglycine Amide from Benzaldehyde and KCN Using Difference of Enzyme Affinity to the Enantiomers
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In general, enzymatic and chemoenzymatic methods for asymmetric synthesis of α-amino acids are performed using highly enantioselective enzymes. The enzymatic reactions using α-aminonitrile as a starting material have been performed using reaction conditions apart from the chemical Strecker synthesis. We developed a new chemoenzymatic method for the asymmetric synthesis of α-amino acids from aldehydes and KCN by performing Strecker synthesis and nitrilase reaction in the same reaction mixture. Nitrilase AY487533 that showed rather low enantioselectivity in hydrolysis of 2-phenylglycinonitrile (2PGN) to 2-phenylglycine (2PG) was utilized in the hydrolysis of aminonitrile formed from benzaldehyde and KCN via 2PGN by Strecker synthesis, preferentially synthesizing (R)-2PG with more than 95 % yield and enantiomeric excess (ee). The method was also utilized for the synthesis of (R)-2-phenylglycine amide ((R)-2PGNH2) from benzaldehyde and KCN by the chemoenzymatic reaction in the presence of a mutated nitrilase AY487533W186A, which catalyzes the conversion of 2PGN to 2PGNH2.
- Kawahara, Nobuhiro,Asano, Yasuhisa
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Read Online
- Clean production method of L-p-hydroxyphenylglycine
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The invention relates to a clean production method of L-p-hydroxyphenylglycine, which comprises the following steps: reacting phenol and sulfamic acid in an alkane solvent to generate phenol ammonium sulfate, adding a glyoxylic acid aqueous solution with the mass concentration of 50%, carrying out addition reaction with the phenol ammonium sulfate, carrying out azeotropic separation on brought-in water, and after the charging is completed, continuously conducting heating and refluxing for 2-5 hours until the glyoxylic acid is completely converted and the ammoniation reaction is completed; adding deionized water into the reaction liquid, and hydrolyzing reactants to generate DL-p-HPG sulfamic acid double salt; and adding a seed crystal and then conducting cooling to obtain a D-p-HPG sulfamic acid double salt crystal, and further neutralizing the D-p-HPG sulfamic acid double salt crystal by ammonia water to obtain a D-p-HPG product with the content of 99.1%-99.7%, and the molar yield of 60%-64%. The synthesis process and the splitting process of the DL-p-HPG are carried out in one pot, so that the generation of waste mother liquor is greatly reduced. According to the method, the sulfamic acid is used for multiple purposes and serves as a catalyst, an aminating agent and a resolving agent for synthesizing the D-p-HPG at the same time, the raw material cost for preparing the D-p-HPG is reduced, the economical efficiency of the process technology is improved, and the method has industrial application prospects.
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Paragraph 0027-0034
(2022/01/24)
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- Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
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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
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supporting information
p. 390 - 398
(2021/01/13)
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- D-Phenylglycine aminotransferase (d-PhgAT)-substrate scope and structural insights of a stereo-inverting biocatalyst used in the preparation of aromatic amino acids
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Enantiopure amines are key building blocks in the synthesis of many pharmaceuticals, so a route to their production is a current goal for biocatalysis. The stereo-inverting d-phenylglycine aminotransferase (d-PhgAT), isolated from Pseudomonas stutzeri ST-201, catalyses the reversible transamination from l-glutamic acid to benzoylformate, yielding α-ketoglutarate and d-phenylglycine (d-Phg). Detailed kinetic analysis revealed a range of amine donor and acceptor substrates that allowed the synthesis of enantiopure aromatic d-amino acids at a preparative scale. We also determined the first X-ray crystal structure of d-PhgAT with its bound pyridoxal 5′-phosphate (PLP) cofactor at 2.25 ? resolution. A combination of structural analysis and site-directed mutagenesis of this class III aminotransferase revealed key residues that are potentially involved in the dual substrate recognition, as well as controlling the stereo-inverting behaviour of d-PhgAT. Two arginine residues (Arg34 and Arg407) are involved in substrate recognition within P and O binding pockets respectively. These studies lay the foundation for further enzyme engineering and promote d-PhgAT as a useful biocatalyst for the sustainable production of high value, aromatic d-amino acids. This journal is
- Akhtar, M. Kalim,Campopiano, Dominic J.,De Cesare, Silvia,Loake, Gary J.,Marles-Wright, Jon,Serpico, Annabel
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p. 6533 - 6543
(2020/11/13)
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- Ultrasound-Controlled Chiral Separation of Four Amino Acids and 2,2,2-Trifluoro-1-(9-anthryl)ethanol
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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
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p. 146 - 149
(2019/02/07)
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- Efficient synthesis of cefadroxil in [Bmim][NTf2]-phosphate cosolvent by magnetic immobilized penicillin G acylase
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For the first time, cefadroxil was synthesized from 7-Amino-3-desacetoxycephalosporanic acid and d-hydroxyphenylglycine methyl ester in [Bmim][NTf2]-phosphate cosolvent capable of dissolving the substrates using the penicillin G acylase (PGA) immobilized on the micrometer-size magnetic polymer microspheres having high activity of 2,083 U/g. The high synthesis/hydrolysis (S/H) ratio of 1.12 was achieved with 79.0% yield, where only the S/H ratio of 0.19 and yield of 20.0% was obtained using free PGA under the identical optimum reaction conditions. Cefadroxil had been synthesized efficiently in [Bmim][NTf2]-phosphate cosolvent by the magnetic immobilized PGA, which illuminated that there are two very critical and essential designs, that is, effective support and suitable solvent system by PGA, in enzymatic synthesis of cefadroxil. Obviously, there is great potential for the magnetic immobilized PGA and ionic liquid solvent in application to biocatalysis.
- Zhaoyu, Zheng,Chunmiao, Hu,Chuanhu, Du,Ping, Xue,Weiwei, Zhang
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p. 1649 - 1657
(2019/11/03)
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- Optical resolution and mechanism using enantioselective cellulose, sodium alginate and hydroxypropyl-β-cyclodextrin membranes
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Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl-β-cyclodextrin were prepared for chiral dialysis separations. After optimizing the membrane material concentrations, the membrane preparation conditions and the feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were obtained for mandelic acid on the cellulose membrane, p-hydroxy phenylglycine on the sodium alginate membrane, and p-hydroxy phenylglycine on the hydroxypropyl-β-cyclodextrin membrane, respectively. To study the optical resolution mechanism, chiral discrimination by membrane adsorption, solid phase extraction, membrane chromatography, high-pressure liquid chromatography ultrafiltration were performed. All of the experimental results showed that the first adsorbed enantiomer was not the enantiomer that first permeated the membrane. The crystal structures of mandelic acid and p-hydroxy phenylglycine are the racematic compounds. We suggest that the chiral separation mechanism of the solid membrane is “adsorption – association – diffusion,” which is able to explain the optical resolution of the enantioselective membrane. This is also the first report in which solid membranes of sodium alginate and hydroxypropyl-β-cyclodextrin were used in the chiral separation of p-hydroxy phenylglycine.
- Yuan, Li-Ming,Ma, Wei,Xu, Mei,Zhao, Hui-Lin,Li, Yuan-Yuan,Wang, Rui-Lin,Duan, Ai-Hong,Ai, Ping,Chen, Xue-Xian
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p. 315 - 324
(2017/05/29)
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- Chromatographic Resolution of α-Amino Acids by (R)-(3,3'-Halogen Substituted-1,1'-binaphthyl)-20-crown-6 Stationary Phase in HPLC
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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
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p. 1037 - 1042
(2017/07/25)
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- Method for synthesizing left-handed p-hydroxyphenyl glycine
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The invention discloses a method for synthesizing left-handed p-hydroxyphenyl glycine. According to the method, mixing-handed p-hydroxyphenyl glycine is taken as a raw material, drinking water is taken as solvent, and D-3-bromine camphorsulfonic acid is taken as a resolving agent. The method comprises the following steps that 1, the mixing-handed p-hydroxyphenyl glycine is heated and dissolved in the drinking water, then the resolving agent is added, and mixing is performed for a reaction to obtain double salt prepared from the mixing-handed p-hydroxyphenyl glycine and the resolving agent; 2, the double salt prepared form the mixing-handed p-hydroxyphenyl glycine and the resolving agent is dissolved in water and then mixed with alkali liquor, and the left-handed p-hydroxyphenyl glycine is obtained through stirring crystallizing, separating, washing and drying. The method has the advantages that the conversion rate of the mixing-handed p-hydroxyphenyl glycine to the left-handed p-hydroxyphenyl glycine can reach 99.9%, the unit consumption of the resolving agent can reach 0.023-0.025, optical rotation of the left-handed p-hydroxyphenyl glycine can reach minus 158 degrees-160 degrees, no right-handed p-hydroxyphenyl glycine is detected out, the product quality is high, and the international enterprise requirements are totally met.
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Paragraph 0022; 0023; 0024
(2016/10/24)
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- NOVEL CRYSTALLINE CEFOPERAZONE INTERMEDIATE
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The present invention relates to a crystalline form of an intermediate for cefoperazone of formula (1) and to a process for the preparation thereof by enzymatic condensation of a 3′-thiosubstituted β-lactam nucleus with a phenylglycine derivative.
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Paragraph 0062
(2015/04/28)
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- Preparation of α-amino acids by oxidative oxazoline-oxazinone rearrangement-hydrogenation (OOOH). Scope and limitations
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The range and scope of the oxidative oxazoline-oxazinone rearrangement-hydrogenation sequence (OOOH)-a short, direct asymmetric synthesis of α-amino acids from carboxylic acids-was explored. The highest yet reported diastereoselectivity for hydrogenation of the oxazinone C=N bond (d.r.=>80:1) is disclosed and rationalized with the aid of ab initio molecular calculations.
- Liu, Chaomin,Molinski, Tadeusz F.
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supporting information; experimental part
p. 2022 - 2027
(2011/11/29)
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- One-pot, regioselective synthesis of substituted arylglycines for kinetic resolution by penicillin G acylase
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Amido-alkylation of electron-rich arenes with phenylacetamide and glyoxylic acid offers an in-expensive route to a large variety of N-phenylacetylated arylglycines that are suited for immediate enzymatic resolution by penicillin G acylase. When performed under mild conditions at 5 °C in acetic acid/HCl, this simple one-pot operation resulted in the formation of single regioisomers only (≥98%). Subsequent kinetic resolution of the amino acid derivatives by penicillin G acylase at pH 8.0 occurred generally with E values >100 and thus furnished free (S)-configurated arylglycines with high enantiomeric purity. The corresponding enantiopure (R)-substrates, easily separable by a phase-selective extraction process, provided the corresponding (R)-enantiomers upon conventional hydrolysis. This one-pot, two-step procedure for arylglycine synthesis, resolution and work-up requires a minimum of equipment and grants rapid access to both enantiopure (S)- and (R)-antipodes of non-natural α-amino acids in small-to large-scale quantities.
- Grundmann, Peter,Fessner, Wolf-Dieter
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experimental part
p. 1729 - 1735
(2009/07/24)
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- Using ionic liquid [EMIM][CH3COO] as an enzyme-'friendly' co-solvent for resolution of amino acids
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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
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p. 2491 - 2498
(2007/10/03)
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- Application of aminoacylase I to the enantioselective resolution of α-amino acid esters and amides
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Aminoacylase I from Aspergillus melleus, a readily available and inexpensive enzyme mainly used in the industrial production of enantiopure L-amino acids from their N-acetyl derivatives, is shown to hydrolyze the esters and amides of natural and non-natural amino acids with high enantioselectivity (for the ester hydrolysis, E is up to 76, in case of amides E >300). The reaction rates of amide and ester hydrolysis are comparable, and in some cases these conversions proceeded even faster than 'traditional' aminoacylase- catalyzed hydrolysis of N-acetyl derivatives thus providing new possibilities for the resolution of the corresponding racemates. This novel approach provides an alternative route for the biocatalytic production of optically active amino acids and their derivatives.
- Youshko, Maxim I.,Van Langen, Luuk M.,Sheldon, Roger A.,Svedas, Vytas K.
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p. 1933 - 1936
(2007/10/03)
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- 3-oxopropane-1-sulphonic acids and sulphonates
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The invention relates to 1,3-disubstituted-3-oxopropane-1-sulfonic acids and sulfonates and enantiomerically inriched forms thereof. The invention further relates to the use of these enantiomerically inriched compounds to resolve mixtures of enantiomers, in particular mixtures of enantiomers of amino-functionalized compounds.
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Page/Page column 12-13
(2008/06/13)
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- Dutch resolution of racemic 4-hydroxy- and 4-fluorophenylglycine with mixtures of phenylglycine and (+)-10-camphorsulfonic acid
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4-Hydroxyphenylglycine and 4-fluorophenylglycine can be resolved with (+)-10-camphorsulfonic acid only if DL- or D-(-)-phenylglycine is added. When using DL-phenylglycine this is co-resolved in this process. In this resolution process mixed crystals are formed of the (+)-10-camphorsulfonic acid salts of the D-(-)-enantiomers of phenylglycine and the para substituted phenylglycines. In the crystal lattice of the mixed salts approximately 25- 30% of the D-(-)-phenylglycine molecules can be randomly replaced by D-(-)- para substituted phenylglycines, resulting in the desired resolution. The overall non-stoichiometric composition of the mixed crystals reflects to some extent the composition in solution. This behaviour is typical for solid solutions. The solid solution behaviour in this so called 'Dutch resolution' is proven by differential scanning calorimetry (DSC), X-ray crystal structure determination and powder diffraction. (C) 2000 Elsevier Science Ltd.
- Kaptein, Bernard,Elsenberg, Henk,Grimbergen, Reinier F. P.,Broxterman, Quirinus B.,Hulshof, Lumbertus A.,Pouwer, Kees L.,Vries, Ton R.
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p. 1343 - 1351
(2007/10/03)
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- New hydantoinases from thermophilic microorganisms - Synthesis of enantiomerically pure D-amino acids
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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
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p. 1257 - 1260
(2007/10/02)
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- Racemization of Optically Active Aromatic N-Acetylamino Acids and Asymmetric Transformation of N-Acetyl-2-(4-hydroxyphenyl)glycine via Salt Formation with Optically Active α-Methylbenzylamine
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The racemization rates of N-acetyl-(S)-tyrosine, N-acetyl-(S)-phenylalanine, N-acetyl-(R)-2-(4-hydroxyphenyl)glycine , N-acetyl-(R)-2-phenylglycine, and N-acetyl-(S)-alanine were measured by use of (RS)-α-methylbenzylamine as base-catalyst.The first-order rate constant for racemization tended to increase with an increase in the polar substituent constant of the N-acetylamino acid side chain.The racemization appeared to be subject to the inductive effect by the side chain.An asymmetric transformation of (RS)-AcHpg by using (R)-MBA, based on the result of racemization, gave an optically pure salt of (R)-AcHpg with (R)-MBA by successive use of the filtrate as the solvent.Optically pure (R)-2-(4-hydroxyphenyl)glycine was separated from the salt in 87-90percent yield based on the starting (RS)-AcHpg.In addition, the asymmetric transformation of (R)-AcHpg was achieved by using (S)-MBA to give optically pure (S)-Hpg in 80percent yield after purification of the salt of (S)-AcHpg with (S)-MBA followed by hydrolysis.
- Shiraiwa, Tadashi,Sakata, Shinji,Natsuyama, Hisashi,Fujishima, Keiko,Miyazaki, Hideya,et al.
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p. 965 - 970
(2007/10/02)
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- STRUCTURE OF COMPLESTATIN, A VERY STRONG INHIBITOR OF PROTEASE ACTIVITY OF COMPLEMENT IN THE HUMAN COMPLEMENT SYSTEM
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The structure of complestatin, which strongly inhibits the protease activity of complements in the human complement system, has been determined as shown in Fig.2 mainly based on HMBC.Its structure is closely related to glycopeptide antibiotics.
- Seto, Haruo,Fujioka, Tomoyuki,Furihata, Kazuo,Kaneko, Isao,Takahashi, Shuji
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p. 4987 - 4990
(2007/10/02)
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- Screening of Microorganism Producing D-p-Hydroxyphenylglicine from DL-5-(p-Hydroxyphenyl)hydantoin
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Microorganism that assymetrically produce D-p- hydroxyphenylglycine (D-HPG) from DL-5-(p-hydroxyphenyl)hydantoin (DL-HPH), an intermediate in the chemical synthesis of DL-HPG, were screened from stock cultures and soil samples.Of the 430 strains of bacteria, yeasts and actinomycetes obtained from our stock cultures, only two, Achromobacter delicatulus AJ-2446 and Achromobacter dendriticum AJ-2447, were capable of producing D-HPG from DL-HPH, but the yields were rather low.A bacterium with high productivity was isolated from a soil sample.It was classified as a bacterium belonging to the genus, Pseudomonas.In the presence of intact cels of Pseudomonas sp.AJ-11220 isolated from soil, which was selected as the best strain, D-HPG was produced from D-, L- and DL-HPH at a molar yield of more than 90 percent.This suggests that racemization and asymetric hydrolysis occured simultaneously in this reaction system.
- Yokozeki, Kenzo,Nakamori, Shigeru,Eguchi, Chikahiko,Yamada, Kazuhiko,Mitsugi, Koji
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p. 355 - 362
(2007/10/02)
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- Mechanism of Asymmetric Production of D-Amino Acids from the Corresponding Hydantoins by Pseudomonas sp.
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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
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p. 721 - 728
(2007/10/02)
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- Optimal Conditions for the Enzymatic Production of D-Amino Acids from the Corresponding 5-Substituted Hydantoins
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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
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p. 715 - 720
(2007/10/02)
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- Asymmetric Transformation of DL-p-Hydroxyphenylglycine by a Combination of Preferential Crystallization and Simultaneous Racemization of the o-Toluenesulfonate
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The asymmetric transformation of DL-p-hydroxyphenylglycine was achieved between two enantiomers by a combination of preferential crystallization of desired enantiomer of p-hydroxyphenylglycine o-toluenesulfonate (HPG.o-Ts) and the simultaneous racemization of the antipode.L-HPG.o-TS was easily racemized by heating at 100 deg C in aqueous 95percent (v/v) acetic acid in the presence of small amounts of salicylaldehyde and free DL-HPG.A supersaturated solution of DL-HPG.o-TS placed under such conditions for racemization was seeded with the crystals of D-HPG.o-TS, and added with DL-HPG and o-toluenesulfonic acid in order to provide contonously the supersaturated of DL-HPG.o-TS as a driving force.As a result, 77.2percent of DL-HPG added was transformed to D-isomer.
- Hongo, Chikara,Tohyama, Masanori,Yoshioka, Ryuzoki,Yamada, Shigeki,Chibata, Ichiro
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p. 433 - 436
(2007/10/02)
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