- Highly stereoselective recognition and deracemization of amino acids by supramolecular self-assembly
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The highly stereoselective supramolecular self-assembly of α-amino acids with a chiral aldehyde derived from binol and a chiral guanidine derived from diphenylethylenediamine (dpen) to form the imino acid salt is reported. This system can be used to cleanly convert D-amino acids into L-amino acids or vice versa at ambient temperature. It can also be used to synthesize α-deuterated D- or L-amino acids. A crystal structure of the ternary complex together with DFT computation provided detailed insight into the origin of the stereoselective recognition of amino acids. A communal effort: A chiral guanidine derivative 1 and a chiral aldehyde 2 underwent self-assembly with amino acids to promote inversion of the stereogenic center of the guest (see scheme). The supramolecular self-assembly exhibited high stereoselectivity for amino acid recognition and was found to be useful for the separation of racemic mixtures of amino acids as well as for their deracemization. Copyright
- So, Soon Mog,Moozeh, Kimia,Lough, Alan J.,Chin, Jik
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- Kinetics of enantioselective liquid-liquid extraction of phenylglycine enantiomers using a BINAP-copper complex as chiral selector
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Kinetic study of reactive extraction of phenylglycine (PhgH) racemate with S-BINAP ((S)-(-)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene)- copper complex (BINAP-Cu) as the chiral selector was performed in a modified Lewis cell. The theory of extraction accompanied by a chemical reaction was applied to achieve insightful understanding of the extraction process. The effects of agitation speed, interface area, pH value of the aqueous phase, initial concentration of PhgH racemate, and initial concentration of BINAP-Cu on the specific rate of extraction were investigated. An extraction course was simulated based on the rate equations. The forward rate constants of 3.14 × 10-5 m3.4 mol-0.7 s-1 for R-PhgH and 4.03 × 10-5 m3.4 mol-0.7 s-1 for S-PhgH, respectively, were found. The modeled extraction course was in good agreement with the experimental one.
- Zhang, Pan-Liang,Luo, Jing-Jing,Tang, Ke-Wen,Yi, Jian-Min
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- Stereoselective hydration of (RS)-phenylglycine nitrile by new whole cell biocatalysts
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Five new bacterial isolates with stereoselective nitrile hydratase activity against (RS)-2-phenylpropionitrile and (RS)-phenylglycine nitrile were investigated. The permeabilized whole cell isolates selectively hydrate the (S)-enantiomer of phenylglycine nitrile with E values of 1.2-5.4. One isolate, which was identified as Pantoea endophytica, produced pure (S)-phenylglycine (>99% ee) as a result of hydrolysis of (S)-phenylglycine amide by an (S)-specific amidase. Surprisingly, in the hydrolysis of (RS)-phenylglycine nitrile, it was found that the (R)-amide was accumulated in excess (21% ee) despite the nitrile hydratase produced by Pantoea endophytica was (S)-selective. The synthesis of pure (R)-phenylglycine (>99% ee) was achieved in time course studies using another Pantoea sp. with (R)-selective amidase. In the case of Nocardioides sp. the intermediate product, (S)-phenylglycine amide, could be produced (52% ee) without its subsequent hydrolysis into the acid due to the apparent absence of any amidase activity.
- Hensel, Martina,Lutz-Wahl, Sabine,Fischer, Lutz
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- Deracemisation of mandelic acid to optically pure non-natural L-phenylglycine via a redox-neutral biocatalytic cascade
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A biocatalytic redox-neutral reaction cascade was designed for the deracemisation of racemic mandelic acid to yield optically pure L-phenylglycine employing three enzymes. The cascade consisted of three steps: a racemisation, an enantioselective oxidation and a stereoselective reductive amination. The enantioselective oxidation of Dmandelic acid to the corresponding oxo acid was coupled with the stereoselective reductive amination of the latter; thus the oxidation as well as the reduction reactions were performed simultaneously. The formal hydrogen abstracted in the first step the oxidation - was consumed in the reductive amination allowing a redox-neutral cascade due to a cascade-internal cofactor recycling. The enantiomers of the starting material were interconverted by a racemase (mandelate racemase) ensuring that in theory 100% of the starting material can be transformed. Using this set-up racemic mandelic acid was transformed to optically pure L-phenylglycine (ee >97%) at 94% conversion without the requirement of any additional redox reagents in stoichiometric amounts.
- Resch, Verena,Fabian, Walter M. F.,Kroutil, Wolfgang
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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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- Directed evolution of formate dehydrogenase and its application in the biosynthesis of L-phenylglycine from phenylglyoxylic acid
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Formate dehydrogenase (FDH) is a D-2?hydroxy acid dehydrogenase, and catalyzes the oxidation of formate to carbon dioxide, coupled with reduction of NAD+ to NADH that plays a key role in the process of NADH regeneration. In order to obtain high activity formate dehydrogenase mutants, the formate dehydrogenase CbFDHC23S was used as the parent to conduct two rounds of directed evolution, and a mutant M2 was obtained which specific activity was about 4 times more than the parent and was more suitable for coenzyme regeneration under physiological conditions. Then, the molecular mechanism of temperature characteristic and catalytic efficiency change was preliminarily elucidated by computer-aided method. Finally, an engineered E. coli strain was established to co-express formate dehydrogenase and L-leucine dehydrogenase and enantioselectively transform phenylglyoxylic acid to give L- phenylglycine (e.e. >99%), the yield and space-time yield of L- phenylglycine can reach 90.46% and 82.07 g?L?1?d?1. This study laid a theoretical foundation for the green biosynthesis of food additives such as chiral alcohols and amino acid derivatives catalyzed by FDH coupling to enhance the regeneration capacity of NADH, reduce the regeneration cost of NADH, and achieve high efficiency and low cost.
- Bai, Fang-Hui,Kan, Yun-Chao,Lu, Yun-Feng,Shi, Hong-Ling,Tang, Cun-Duo,Xie, Yu-Li,Yang, Tian-Tian,Yao, Lun-Guang,Zhang, Si-Pu,Zhang, Zheng-Hua
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- Semi-rational hinge engineering: modulating the conformational transformation of glutamate dehydrogenase for enhanced reductive amination activity towards non-natural substrates
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The active site is the common hotspot for rational and semi-rational enzyme activity engineering. However, the active site represents only a small portion of the whole enzyme. Identifying more hotspots other than the active site for enzyme activity engineering should aid in the development of biocatalysts with better catalytic performance. Glutamate dehydrogenases (GluDHs) are promising and environmentally benign biocatalysts for the synthesis of valuable chirall-amino acids by asymmetric reductive amination of α-keto acids. GluDHs contain an inter-domain hinge structure that facilitates dynamic reorientations of the domains relative to each other. Such hinge-bending conformational motions of GluDHs play an important role in regulating the catalytic activity. Thus, the hinge region represents a potential hotspot for catalytic activity engineering for GluDHs. Herein, we report semi-rational activity engineering of GluDHs with the hinge region as the hotspot. Mutants exhibiting significantly improved catalytic activity toward several non-natural substrates were identified and the highest activity increase reached 104-fold. Molecular dynamics simulations revealed that enhanced catalytic activity may arise from improving the open/closed conformational transformation efficiency of the protein with hinge engineering. In the batch production of three valuablel-amino acids, the mutants exhibited significantly improved catalytic efficiency, highlighting their industrial potential. Moreover, the catalytic activity of several active site tailored GluDHs was also increased by hinge engineering, indicating that hinge and active site engineering are compatible. The results show that the hinge region is a promising hotspot for activity engineering of GluDHs and provides a potent alternative for developing high-performance biocatalysts toward chirall-amino acid production.
- Liu, Yayun,Meng, Lijun,Wu, Jianping,Yang, Lirong,Yin, Xinjian,Zhou, Haisheng
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p. 3376 - 3386
(2020/06/09)
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- Process Optimisation Studies and Aminonitrile Substrate Evaluation of Rhodococcus erythropolis SET1, A Nitrile Hydrolyzing Bacterium
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A comprehensive series of optimization studies including pH, solvent and temperature were completed on the nitrile hydrolyzing Rhodococcus erythropolis bacterium SET1 with the substrate 3-hydroxybutyronitrile. These identified temperature of 25 °C and pH of 7 as the best conditions to retain enantioselectivity and activity. The effect of the addition of organic solvents to the biotransformation mixture was also determined. The results of the study suggested that SET1 is suitable for use in selected organo-aqueous media at specific ratios only. The functional group tolerance of the isolate with unprotected and protected β-aminonitriles, structural analogues of β-hydroxynitriles was also investigated with disappointingly poor isolated yields and selectivity obtained. The isolate was further evaluated with the α- aminonitrile phenylglycinonitrile generating acid in excellent yield and ee (>99 % (S) – isomer and 50 % yield). A series of pH studies with this substrate indicated pH 7 to be the optimum pH to avoid product and substrate degradation.
- Coady, Tracey M.,Coffey, Lee,Kinsella, Michael,Lennon, Claire M.,Mareya, Tatenda M.,O'Reilly, Catherine
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p. 512 - 520
(2020/10/02)
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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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- 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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p. 5014 - 5020
(2018/10/20)
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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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supporting information
p. 1037 - 1042
(2017/07/25)
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- Highly efficient enantioselective liquid-liquid extraction of 1,2-amino-alcohols using SPINOL based phosphoric acid hosts
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Access to enantiopure compounds on large scale in an environmentally friendly and cost-efficient manner remains one of the greatest challenges in chemistry. Resolution of racemates using enantioselective liquid-liquid extraction has great potential to meet that challenge. However, a relatively feeble understanding of the chemical principles and physical properties behind this technique has hampered the development of hosts possessing sufficient resolving power for their application to large scale processes. Herein we present, employing the previously untested SPINOL based phosphoric acids host family, an in depths study of the parameters affecting the efficiency of the resolution of amino-alcohols in the optic of further understanding the core principles behind ELLE. We have systematically investigated the dependencies of the enantioselection by parameters such as the choice of solvent, the temperature, as well as the pH and bring to light many previously unsuspected and highly intriguing interactions. Furthermore, utilizing these new insights to our advantage, we developed novel, highly efficient, extraction and resolving protocols which provide remarkable levels of enantioselectivity. It was shown that the extraction is catalytic in host by demonstrating transport in a U-tube and finally it was demonstrated how the solvent dependency could be exploited in an unprecedented triphasic resolution system.
- Pinxterhuis, Erik B.,Gualtierotti, Jean-Baptiste,Heeres, Hero J.,De Vries, Johannes G.,Feringa, Ben L.
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p. 6409 - 6418
(2017/08/29)
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- One-Pot Enantioselective Synthesis of d-Phenylglycines from Racemic Mandelic Acids, Styrenes, or Biobased l-Phenylalanine via Cascade Biocatalysis
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Enantiopure d-phenylglycine and its derivatives are an important group of chiral amino acids with broad applications in thepharmaceutical industry. However, the existing synthetic methods for d-phenylglycine mainly rely on toxic cyanide chemistry and multistep processes. To provide green and safe alternatives, we envisaged cascade biocatalysis for the one-pot synthesis of d-phenylglycine from racemic mandelic acid, styrene, and biobased l-phenylalanine, respectively. Recombinant Escherichia coli (LZ110) was engineered to coexpress four enzymes to catalyze a 3-step reaction in one pot, transforming mandelic acid (210 mM) to give enantiopure d-phenylglycine in 29.5 g L?1 (195 mM) with 93% conversion. Using the same whole-cell catalyst, twelve other d-phenylglycine derivatives were also produced from the corresponding mandelic acid derivatives in high conversion (58–94%) and very high ee (93–99%). E. coli (LZ116) expressing seven enzymes was constructed for the transformation of styrene to enantiopure d-phenylglycine in 80% conversion via a one-pot 6-step cascade biotransformation. Twelve substituted d-phenylglycines were also produced from the corresponding styrene derivatives in high conversion (45–90%) and very high ee (92–99%) via the same cascade reactions. A nine-enzymeexpressing E. coli (LZ143) was engineered to transform biobased l-phenylalanine to enantiopure d-phenylglycine in 83% conversion via a one-pot 8-step transformation. Preparative biotransformations were also demonstrated. The high-yielding synthetic methods use cheap and green reagents (ammonia, glucose, and/or oxygen), and E. coli whole-cell catalysts, thus providing green and useful alternative methods for manufacturing d-phenylglycine. (Figure presented.).
- Zhou, Yi,Wu, Shuke,Li, Zhi
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p. 4305 - 4316
(2017/11/21)
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- Efficient access to l-phenylglycine using a newly identified amino acid dehydrogenase from: Bacillus clausii
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An amino acid dehydrogenase from Bacillus clausii (BcAADH) was identified and overexpressed in Escherichia coli BL21(DE3) for the preparation of l-phenylglycine from benzoylformic acid. Recombinant BcAADH was purified to homogeneity and characterized. BcAADH could catalyse reductive amination and oxidative deamination at optimum pHs of 9.5 and 10.5. Furthermore, BcAADH has a broad substrate spectrum, displaying activities toward various aromatic and aliphatic keto acids. When coexpressed with glucose dehydrogenase from Bacillus megaterium, the potential application of BcAADH in the preparation of l-phenylglycine was investigated at a high substrate loading and low biocatalyst addition. As much as 400 mM benzoylformic acid could be fully reduced into l-phenylglycine within 6 h at >99.9% ee. With merely 0.5 g DCW L-1, 200 mM benzoylformic acid was completely reduced, resulting in a substrate to biocatalyst ratio of 60 g g-1, environmental factor of 4.7 and 91.7% isolation yield at gram scale. This study provides guidance for the application of BcAADH in the synthesis of chiral non-natural amino acids.
- Cheng, Jun,Xu, Guochao,Han, Ruizhi,Dong, Jinjun,Ni, Ye
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p. 80557 - 80563
(2016/11/15)
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- Cascade Biocatalysis for Sustainable Asymmetric Synthesis: From Biobased l-Phenylalanine to High-Value Chiral Chemicals
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Sustainable synthesis of useful and valuable chiral fine chemicals from renewable feedstocks is highly desirable but remains challenging. Reported herein is a designed and engineered set of unique non-natural biocatalytic cascades to achieve the asymmetric synthesis of chiral epoxide, diols, hydroxy acid, and amino acid in high yield and with excellent ee values from the easily available biobased l-phenylalanine. Each of the cascades was efficiently performed in one pot by using the cells of a single recombinant strain over-expressing 4–10 different enzymes. The cascade biocatalysis approach is promising for upgrading biobased bulk chemicals to high-value chiral chemicals. In addition, combining the non-natural enzyme cascades with the natural metabolic pathway of the host strain enabled the fermentative production of the chiral fine chemicals from glucose.
- Zhou, Yi,Wu, Shuke,Li, Zhi
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supporting information
p. 11647 - 11650
(2016/11/17)
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- Synthesis of Air- and Moisture-Stable, Storable Chiral Oxorhenium Complexes and Their Application as Catalysts for the Enantioselective Imine Reduction
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Air-/moisture-stable, crystalline, and storable chiral salicyloxazoline based oxorhenium(V) complexes have been synthesized and their catalytic application for the asymmetric reduction of ketimines using hydrosilane as hydride source is disclosed. A broad substrate scope, high yields, and excellent enantioselectivities (up to 99 %) are attained. Furthermore, the syntheses of enantiopure α-amino esters, γ- and δ-lactams, and isoindolinones have also been carried out using this methodology. Finally, the method has been applied to synthetic targets of pharmaceutical relevance, such as R-(+)-salsolidine and R-(+)-crispine A.
- Das, Braja Gopal,Nallagonda, Rajender,Dey, Dhananjay,Ghorai, Prasanta
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p. 12601 - 12605
(2015/09/01)
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- Stereoselective synthesis of arylglycine derivatives via palladium-catalyzed α-arylation of a chiral nickel(II) glycinate
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A practical and efficient stereoselective synthesis of arylglycine derivatives was realized via palladium-catalyzed α-arylation of a chiral nickel(II) glycinate complex with aryl bromides. The structurally diverse arylglycine products were obtained in excellent isolated yields and with good diastereoselectivity. A simple acidic hydrolysis furnished optically pure arylglycines in high yield, and the chiral ligand (S)-BPB could be efficiently recovered and reused.
- Zhang, Fan,Sun, Hengzhi,Song, Zhuang,Zhou, Shuxi,Wen, Xiaoan,Xu, Qing-Long,Sun, Hongbin
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p. 4459 - 4464
(2015/05/13)
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- Nitrilases
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The invention relates to nitrilases and to nucleic acids encoding the nitrilases. In addition, methods of designing new nitrilases and methods of use thereof are also provided. The nitrilases have increased activity and stability at increased pH and temperature.
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Paragraph 0495
(2015/09/22)
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- Stereoselective synthesis of l-tert-leucine by a newly cloned leucine dehydrogenase from Exiguobacterium sibiricum
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A leucine dehydrogenase from Exiguobacterium sibiricum (EsLeuDH) was discovered by genome mining approach. The EsLeuDH was overexpressed in Escherichia coli BL21, purified to homogeneity and characterized. This enzyme showed good thermostability with a half-life of 3.1 h at 60 °C. Furthermore, EsLeuDH has a broad spectrum of substrate specificity, showing activities toward many aliphatic α-keto acids and L-amino acids, in addition to some aryl α-keto acids and aryl α-amino acids, such as α-oxobenzeneacetic and l-phenylglycine. The EsLeuDH was successfully coexpressed with Bacillus megaterium glucose dehydrogenase (BmGDH) in Escherichia coli BL21 for the production of l-tert-leucine. By using the coexpressed whole cells, a decagram preparation of l-tert-leucine was performed at a substrate concentration of 0.6 M (78.1 g L-1) in 1 L scale with 99% conversion after 5.5 h, resulting in 80.1% yield and > 99% ee (enantiomeric excess).2014 Published by Elsevier B.V.
- Li, Jing,Pan, Jiang,Zhang, Jie,Xu, Jian-He
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- Amidohydrolase Process: Expanding the use of l-N-carbamoylase/N-succinyl- amino acid racemase tandem for the production of different optically pure l-amino acids
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A bienzymatic system comprising an N-succinylamino acid racemase from Geobacillus kaustophilus CECT4264 (GkNSAAR) and an enantiospecific l-N-carbamoylase from Geobacillus stearothermophilus CECT43 (BsLcar) has been developed. This biocatalyst has been able to produce optically pure natural and non-natural l-amino acids starting from racemic mixtures of N-acetyl-, N-formyl- and N-carbamoyl-amino acids by dynamic kinetic resolution. The fastest conversion rate was found with N-formyl-amino acids, followed by N-carbamoyl- and N-acetyl-amino acids, and GkNSAAR proved to be the limiting step of the system due to its lower specific activity. Metal ion cobalt was essential for the activity of the biocatalyst and the system was optimally active when Co 2+ was added directly to the reaction mixture. The optimum pH for the biocatalyst proved to be 8.0, for both N-formyl- and N-carbamoyl-amino acid substrates, whereas optimum temperature ranges were 45-55 °C for N-formyl-amino acids and 55-70 °C for N-carbamoyl-derivatives. The bienzymatic system was equally efficient in converting aromatic and aliphatic substrates. Total conversion was also achieved using high substrate concentrations (100 and 500 mM) with no noticeable inhibition. This "Amidohydrolase Process" enables the production of both natural and non-natural l-amino acids from a broad substrate spectrum with yields of over 95%.
- Soriano-Maldonado, Pablo,Rodríguez-Alonso, María José,Hernández-Cervantes, Carmen,Rodríguez-García, Ignacio,Clemente-Jiménez, Josefa María,Rodríguez-Vico, Felipe,Martínez-Rodríguez, Sergio,Las Heras-Vázquez, Francisco Javier
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p. 1281 - 1287
(2014/07/22)
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- High yield synthesis of d-phenylglycine and its derivatives by nitrilase mediated dynamic kinetic resolution in aqueous-1-octanol biphasic system
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A strategy of nitrilase mediated dynamic kinetic resolution toward the synthesis of d-phenylglycine was developed, using aqueous-1-octanol biphasic system. Due to the efficient suppression of the decomposition of phenylglycinonitrile, a maximum yield of 81% is obtained. This result indicates that the nitrilase mediated dynamic kinetic resolution is a promising method toward the synthesis of d-phenylglycine and its derivatives.
- Qiu, Jian,Su, Erzheng,Wang, Wei,Wei, Dongzhi
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p. 1448 - 1451
(2014/03/21)
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- Large α-aminonitrilase activity screening of nitrilase superfamily members: Access to conversion and enantiospecificity by LC-MS
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A high-throughput screening for the identification of nitrilases demonstrating activity towards alpha-aminonitriles is reported. A LC-MS assay giving access to both conversion and enantiospecificity was developed. 588 candidate enzymes were screened as cell lysates against six alpha-aminonitriles in 96-well microplates. The candidate enzymes were selected following two criteria, their sequence identity with a set of known nitrilases or their phylogenetic position among the nitrilase superfamily. Five enzymes were identified and found to hydrolyse alpha-aminonitrile into the corresponding alpha-aminoacid. The substrate range was found to be very narrow as only two different alpha-aminonitriles, 2-aminovaleronitrile and 2-amino-2- phenylacetonitrile, were found to be substrates. The biocatalytic capabilities of three enzymes were further investigated and the best result was obtained with an enzyme from Burkholderia xenovorans catalysing the enantiospecific hydrolysis of 2-aminovaleronitrile into (S)-norvaline with excellent conversion and enantiomeric excess.
- Bordier, Franck,Stam, Mark,Darii, Ekaterina,Tricot, Sabine,Fossey, Aurelie,Rohault, Johanna,Debard, Adrien,Mariage, Aline,Pellouin, Virginie,Petit, Jean-Louis,Perret, Alain,Vallenet, David,Salanoubat, Marcel,Weissenbach, Jean,Vergne-Vaxelaire, Carine,De Berardinis, Veronique,Zaparucha, Anne
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- Biocatalytic asymmetric synthesis of unnatural amino acids through the cascade transfer of amino groups from primary amines onto keto acids
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Flee to the hills: An unfavorable equilibrium in the amino group transfer between amino acids and keto acids catalyzed by α-transaminases was successfully overcome by coupling with a ω-transaminase reaction as an equilibrium shifter, leading to efficient asymmetric synthesis of diverse unnatural amino acids, including L-tert-leucine and D-phenylglycine. Copyright
- Park, Eul-Soo,Dong, Joo-Young,Shin, Jong-Shik
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p. 3538 - 3542
(2014/01/06)
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- SEPARATING AGENT FOR CHROMATOGRAPHY
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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.
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Paragraph 0074; 0075
(2013/08/15)
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- Efficient kinetic resolution of amino acids catalyzed by lipase AS 'Amano' via cleavage of an amide bond
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Herein the efficient kinetic resolution of non-natural alpha-amino acids catalyzed by lipase AS 'Amano' via cleaving the amide bond is reported. The starting materials were the corresponding amino acid amides and the amino acids were generated with ees of up to 99% with E values of >600. These results indicated that the lipase AS 'Amano' could be a powerful amide hydrolase for the kinetic resolution of amino acid starting from the corresponding amino acid amides.
- Wang, Bo,Liu, Yanfeng,Zhang, Dela,Feng, Yuhong,Li, Jiacheng
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p. 1338 - 1342,5
(2020/09/16)
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- Enzymatic synthesis of chiral phenylalanine derivatives by a dynamic kinetic resolution of corresponding amide and nitrile substrates with a multi-enzyme system
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Mutant α-amino-ε-caprolactam (ACL) racemase (L19V/L78T) from Achromobacter obae with improved substrate specificity toward phenylalaninamide was obtained by directed evolution. The mutant ACL racemase and thermostable mutant D-amino acid amidase (DaaA) from Ochrobactrum anthropi SV3 co-expressed in Escherichia coli (pACLmut/pDBFB40) were utilized for synthesis of (R)-phenylalanine and non-natural (R)-phenylalanine derivatives (4-OH, 4-F, 3-F, and 2-F-Phe) by dynamic kinetic resolution (DKR). Recombinant E. coli with DaaA and mutant ACL racemase genes catalyzed the synthesis of (R)-phenylalanine with 84% yield and 99% ee from (RS)-phenylalaninamide (400 mM) in 22 h. (R)-Tyrosine and 4-fluoro-(R)-phenylalanine were also efficiently synthesized from the corresponding amide compounds. We also co-expresed two genes encoding mutant ACL racemase and L-amino acid amidase from Brevundimonas diminuta in E. coli and performed the efficient production of various (S)-phenylalanine derivatives. Moreover, 2-aminophenylpropionitrile was converted to (R)-phenylalanine by DKR using a combination of the non-stereoselective nitrile hydratase from recombinamt E. coli and mutant ACL racemase and DaaA from E. coli encoding mutant ACL racemase and DaaA genes. Copyright
- Yasukawa, Kazuyuki,Asano, Yasuhisa
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p. 3327 - 3332
(2013/01/15)
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- Preparation of cross-linked enzyme aggregates of l-aminoacylase via co-aggregation with polyethyleneimine
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l-Aminoacylase from Aspergillus melleus was co-aggregated with polyethyleneimine and subsequently cross-linked with glutaraldehyde to obtain aminoacylase-polyethyleneimine cross-linked enzyme aggregates (termed as AP-CLEA). Under the optimum conditions, AP-CLEA expressed 74.9% activity recovery and 81.2% aggregation yield. The said method of co-aggregation and cross-linking significantly improved the catalytic stability of l-aminoacylase with respect to temperature and storage. AP-CLEA were employed for enantioselective synthesis of three unnatural amino acids (namely: phenylglycine, homophenylalanine and 2-naphthylalanine) via chiral resolution of their ester-, amide- and N-acetyl derivatives. The enantioselectivity of AP-CLEA was the highest for hydrolysis of amino acid amides; was moderate for hydrolysis of N-acetyl amino acids and was the least for hydrolysis of amino acid esters. Furthermore, AP-CLEA were found to retain more than 92% of the initial activity after five consecutive batches of (RS)-homophenylalanine hydrolysis suggesting an adequate operational stability of the biocatalyst.
- Vaidya, Bhalchandra K.,Kuwar, Suyog S.,Golegaonkar, Sandeep B.,Nene, Sanjay N.
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experimental part
p. 184 - 191
(2012/03/22)
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- Chiral imprinting with amino acids of ordered mesoporous silica exhibiting enantioselectivity after calcination
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Chiral ordered mesoporous silica (COMS) was synthesized in basic media by combining tetraethyl orthosilicate and quaternized aminosilane (with a templating role) silica sources together with four different standard amino acids (arginine, histidine, isoleucine, and proline). Besides the hexagonal MCM-41-type structure, narrow pore size distribution, and high specific surface area, it was found that these solids have potential for enantiomeric separation because of the transference of chirality from the amino acid to the silica. This is illustrated by the resolution of several racemic mixtures (those of proline, isoleucine, trans-4-hydroxyproline, pipecolic acid, valine, leucine, and phenylglycine) with the calcined COMS prepared with l-proline. The opposite behavior observed in induced circular dichroism experiments with calcined COMS, obtained using both enantiomers of proline, confirmed their chiral nature. The high number and variety of existing amino acids, and chiral organic compounds in general, makes these ordered silicas attractive for the production of enantiopure substances.(Figure Presented)
- Lacasta, Susana,Sebastian, Victor,Casado, Clara,Mayoral, Alvaro,Romero, Pilar,Larrea, Angel,Vispe, Eugenio,Lopez-Ram-De-Viu, Pilar,Uriel, Santiago,Coronas, Joaquin
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scheme or table
p. 1280 - 1287
(2012/02/15)
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- Asymmetric strecker synthesis of α-arylglycines
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A practically simple three-component Strecker reaction for the asymmetric synthesis of enantiopure α-arylglycines has been developed. Addition of a range of aryl-aldehydes to a solution of sodium cyanide and (S)-1-(4- methoxyphenyl)ethylamine affords highly crystalline (S,S)-α-aminonitriles that are easily obtained in diastereomerically pure form. Heating the resultant (S,S)-α-aminonitriles in 6 M aqueous HCl at reflux resulted in cleavage of their chiral auxiliary fragments and concomitant hydrolysis of their nitrile groups to afford enantiopure (S)-α-arylglycines. The enantiopurities of these (S)-α-arylglycines were determined via derivatization of their corresponding methyl esters with 2-formylphenylboronic acid and (S)-BINOL, followed by 1H NMR spectroscopic analysis of the resultant mixtures of diastereomeric iminoboronate esters.
- Perez-Fuertes, Yolanda,Taylor, James E.,Tickell, David A.,Mahon, Mary F.,Bull, Steven D.,James, Tony D.
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p. 6038 - 6047
(2011/10/08)
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- Totally diastereoselective addition of aryl Grignard reagents to the nitrone-based chiral glycine equivalent MiPNO
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The reaction of the chiral nitrone MiPNO (2-isopropyl-2,3-dimethyl-1-oxy-2, 3-dihydro-imidazol-4-one) with Grignard reagents is totally diastereoselective. Using simple and functionalized arylmagnesium reagents, enantiopure hydroxylamines were obtained in fair to good yields, which in turn could be easily transformed into new chiral ketonitrones. The preparation of enantiopure l-phenylglycine derivatives is also described.
- Thiverny, Maryse,Farran, Daniel,Philouze, Christian,Blandin, Veronique,Chavant, Pierre Y.
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p. 1274 - 1281
(2011/11/28)
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- Alcaligenes faecalis penicillin G acylase-catalyzed enantioselective acylation of dl-phenylalanine and derivatives in aqueous medium
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A new strategy based on enantioselective acylation properties of relatively unknown penicillin G acylase from Alcaligenes faecalis has been developed for the production of pharmacologically interesting enantiomerically pure d-phenylalanine. In order to get high reaction rate and enantioselectivity, two key factors (pH and temperature) and eight different acyl donors were optimized, and the optimal acylation reaction was carried out at pH 10, 35 °C, using phenylacetamide as the acyl donor. This enantioselective acylating method is also illustrated by the effective production of five different p-substituted phenylalanine derivatives in enantiopure.
- Gong, Xiangyu,Su, Erzheng,Wang, Pixiang,Wei, Dongzhi
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supporting information; experimental part
p. 5398 - 5402
(2011/10/19)
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- Highly enantioselective titanium-catalyzed cyanation of imines at room temperature
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(Figure presented) A highly active and enantioselective titanium-catalyzed cyanatlon of imines at room temperature Is described. The catalyst used Is a partially hydrolyzed titanium alkoxide (PHTA) precatalyst together with a readily available N-salicyl-β-aminoalcohol ligand. Up to 98% ee was obtained with quantitative yields In 15 min of reaction time using 5 mol % of the catalyst. Various N-protecting groups such as benzyl, benzhydryl, Boc, and PMP are tolerated.
- Seayad, Abdul Majeed,Ramalingam, Balamurugan,Yoshinaga, Kazuhiko,Nagata, Takushi,Chai, Christina L. L.
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supporting information; experimental part
p. 264 - 267
(2010/03/24)
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- A remarkable titanium-catalyzed asymmetric strecker reaction using hydrogen cyanide at room temperature
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Close to perfect enantioselectivity (up to 98% ee) is obtained for the formation of amino nitrites using hydrogen cyanide (HCN) as the cyanide source at room temperature for the first time. In an operationally simple process, the catalyst generated from a partially hydrolyzed titanium alkoxide (PHTA) and (S)-N-salicyl-ss-amino alcohol ligand, catalyzes the cyanation of imines in a short reaction time.
- Ramalingam, Balamurugan,Seayad, Abdul Majeed,Chuanzhao, Li,Garland, Marc,Yoshinaga, Kazuhiko,Wadamoto, Manabu,Nagata, Takushi,Chai, Christina L. L.
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supporting information; scheme or table
p. 2153 - 2158
(2010/11/04)
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- Crystallisation-induced asymmetric transformation (CIAT) for the synthesis of dipeptides containing homophenylalanine
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A novel synthesis of highly enantioenriched dipeptides containing homophenylalanine is described. The process involves a crystallisation-induced asymmetric transformation (CIAT) in a Michael addition followed by exhaustive reduction. A unique example of a formally stereodivergent CIAT in conjugate addition of an achiral N-nucleophile to enantiomerically pure Michael acceptor has been discovered.
- Jakubec, Pavol,Berkes, Dusan
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p. 2807 - 2815
(2011/03/18)
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- Amino ester hydrolase from Xanthomonas campestris pv. campestris, ATCC 33913 for enzymatic synthesis of ampicillin
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α-Amino ester hydrolases (AEH) are a small class of proteins, which are highly specific for hydrolysis or synthesis of α-amino containing amides and esters including β-lactam antibiotics such as ampicillin, amoxicillin, and cephalexin. A BLAST search revealed the sequence of a putative glutaryl 7-aminocephalosporanic acid (GL-7-ACA) acylase 93% identical to a known AEH from Xanthomonas citri. The gene, termed gaa, was cloned from the genomic DNA of Xanthomonas campestris pv. campestris sp. strain ATCC 33913 and the corresponding protein was expressed into Escherichia coli. The purified protein was able to perform both hydrolysis and synthesis of a variety of α-amino β-lactam antibiotics including (R)-ampicillin and cephalexin, with optimal ampicillin hydrolytic activity at 25 °C and pH 6.8, with kinetic parameters of kcat of 72.5 s-1 and KM of 1.1 mM. The synthesis parameters α, βo, and γ for ampicillin, determined here first for this class of proteins, are α = 0.25, βo = 42.8 M-1, and γ = 0.23, and demonstrate the excellent synthetic potential of these enzymes. An extensive study of site-directed mutations around the binding pocket of X. campestris pv. campestris AEH strongly suggests that mutation of almost any first-shell amino acid residues around the active site leads to inactive enzyme, including Y82, Y175, D207, D208, W209, Y222, and E309, in addition to those residues forming the catalytic triad, S174, H340, and D307.
- Blum, Janna K.,Bommarius, Andreas S.
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experimental part
p. 21 - 28
(2010/12/19)
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- (9H-fluoren-9-yl)methanesuIfonyl (Fms): An amino protecting group complementary to Fmoc
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A sulfonamide-based protecting group (PG), (9H-fluoren-9yl)methanesulfonyl (Fms), which can be used in a similar way to the well-established Fmoc PG, was developed. The advantages of this new PG were demonstrated in the successful formation of a phosphonamide between an N-Fmsprotected a-phosphonoalanine monoester and secondary alkylamines, including (R)-2-phenylethylamine, (S)-phenylalanine iert-butyl ester (H-Phe-OtBu), H-Pro-Gly-OtBu, and H-Phe-Phe-OtBu, without formation of oxazaphospholine, which is a serious problem associated with the Fmoc PG. The success should pave the way to the solid-phase synthesis of unnatural peptides substituted with a-amino phosphonic acid (AP) at essentially any arbitrary position without significant modification of the Fmoc-based chemistry that has been accumulated since Carpino's report in 1970. The N-Fms-AP monomer would attract much attention in the field of peptide mimetics.
- Ishibashi, Yoshitaka,Miyata, Kengo,Kitamura, Masato
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scheme or table
p. 4201 - 4204
(2010/10/02)
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- Formation and hydrolysis of amide bonds by lipase A from Candida antarctica; Exceptional features
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Various commercial lyophilized and immobilized preparations of lipase A from Candida antarctica (CAL-A) were studied for their ability to catalyze the hydrolysis of amide bonds in N-acylated α-amino acids, 3-butanamidobutanoic acid (β-amino acid) and its ethyl ester. The activity toward amide bonds is highly untypical of lipases, despite the close mechanistic analogy to amidases which normally catalyze the corresponding reactions. Most CAL-A preparations cleaved amide bonds of various substrates with high enantioselectivity, although high variations in substrate selectivity and catalytic rates were detected. The possible role of contaminant protein species on the hydrolytic activity toward these bonds was studied by fractionation and analysis of the commercial lyophilized preparation of CAL-A (Cat#ICR-112, Codexis). In addition to minor impurities, two equally abundant proteins were detected, migrating on SDS-PAGE a few kDa apart around the calculated size of CAL-A. Based on peptide fragment analysis and sequence comparison both bands shared substantial sequence coverage with CAL-A. However, peptides at the C-terminal end constituting a motile domain described as an active-site flap were not identified in the smaller fragment. Separated gel filtration fractions of the two forms of CAL-A both catalyzed the amide bond hydrolysis of ethyl 3-butanamidobutanoate as well as the N-acylation of methyl pipecolinate. Hydrolytic activity towards N-acetylmethionine was, however, solely confined to the fractions containing the truncated form of CAL-A. These fractions were also found to contain a trace enzyme impurity identified in sequence analysis as a serine carboxypeptidase. The possible role of catalytic impurities versus the function of CAL-A in amide bond hydrolysis is further discussed in the paper. The Royal Society of Chemistry 2010.
- Liljeblad, Arto,Kallio, Pauli,Vainio, Marita,Niemi, Jarmo,Kanerva, Liisa T.
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scheme or table
p. 886 - 895
(2010/06/20)
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- Chiral separation of underivatized amino acids by reactive extraction with palladium-BINAP complexes
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(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.
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experimental part
p. 6526 - 6533
(2010/03/01)
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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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- Synthesis of optically active α-methylamino acids and amides through biocatalytic kinetic resolution of amides
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Catalyzed by Rhodococcus sp. AJ270, a nitrile hydratase and amidase containing microbial whole-cell catalyst, under very mild conditions, a number of racemic α-methylamino amides were resolved into the corresponding optically active (S)-(+)-α-methylamino acids and (R)-(-)-α- methylamino amides. The steric requirement of the amidase against α-amino phenylacetamides bearing methyl group(s) at α-amino nitrogen and/or α-carbon was also studied. Coupled with the chemical hydrolysis of amide, the biotransformation process provided a direct synthesis of α-methylamino acids in both enantiomeric forms from readily available racemic amides.
- Wang, Mei-Xiang,Liu, Jun,Wang, De-Xian,Zheng, Qi-Yu
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p. 2409 - 2416
(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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- Chemoenzymatic approaches to the dynamic kinetic asymmetric synthesis of aromatic amino acids
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Enzymatic approaches for the production of amino acids by nitrilases are described. Dynamic kinetic asymmetric synthesis conditions were established for the aromatic aminonitriles, phenylglycinonitrile and 4- fluorophenylglycinonitrile, at high pH to produce the corresponding amino acid products in high enantiomeric excess. N-Acylation of aromatic aminonitriles led to spontaneous racemization at pH 8, allowing preferential enzymatic hydrolysis of the (R)-enantiomer to afford the product N-acylamino acids in up to 99% enantiomeric excess (ee).
- Chaplin, Jennifer A.,Levin, Michael D.,Morgan, Brian,Farid, Nancy,Li, Jen,Zhu, Zuolin,McQuaid, Jeff,Nicholson, Lawrence W.,Rand, Cynthia A.,Burk, Mark J.
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p. 2793 - 2796
(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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- Novel enantioselective synthesis of both enantiomers of furan-2-yl amines and amino acids
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A new enantioselective synthesis of furan-2-yl amines and amino acids is described, in which the key step is the oxazaborolidine-catalyzed enantioselective reduction of O-benzyl (E)- and (Z)-furan-2-yl ketone oximes to the corresponding chiral amines. The chirality of the furan-2-yl amines is fully controlled by the appropriate choice of the geometrical isomer of the O-benzyl oxime. Oxidation of the furan ring furnished amino acids in high yields.
- Demir, Ayhan S.,Sesenoglu, Oezge,Uelkue, Dincer,Arici, Cengiz
-
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- Glutaryl Acylases: One-Reaction Enzymes or Versatile Enantioselective Biocatalysts?
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A significant broad substrate specificity, that crosses over the usual β-lactam derivatives, has been observed with an industrial glutaryl-7-aminocephalosporanic acid acylase (GA). This enzyme possesses significant enantioselective amidase and even esterase activity, with a stereopreference for the S-enantiomer. The easy separation of products from unreacted reagents, possessing different physical-chemical properties, is achieved by solvent extraction, avoiding chromatography or distillation during reaction work-up.
- Raimondi, Stefano,Monti, Daniela,Pagnoni, Ugo Maria,Riva, Sergio
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p. 783 - 789
(2007/10/03)
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- Practical and convenient enzymatic synthesis of enantiopure α-amino acids and amides
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Catalyzed by the nitrile hydratase and the amidease in Rhodococcus sp. AJ270 cells under very mild conditions, a number of α-aryl- and α-alkyl-substituted DL-glycine nitriles 1 rapidly underwent a highly enantioselective hydrolysis to afford D-(-)-α-amino acid amides 2 and L-(+)-α-amino acids 3 in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of a high L-enantioselective amidase and a low enantioselective nitrile hydratase. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects. Coupled with chemical hydrolysis of D-(-)-α-phenylglycine amide, biotransformation of DL-phenylglycine nitrile was applied in practical scale to produce both D- and L-phenylglycines in high optical purity.
- Wang, Mei-Xiang,Lin, Shuang-Jun
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p. 6542 - 6545
(2007/10/03)
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- Deracemisation and stereoinversion of alpha-amino acids using D-amino acid oxidase and hydride reducing agents.
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The deracemisation and stereoinversion of both cyclic and acyclic DL-alpha-amino acids, using porcine kidney D-amino acid oxidase (DAAO) and a hydride reducing agent (NaCNBH3-NaBH4), has been investigated.
- Beard, Timothy M,Turner, Nicholas J
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p. 246 - 247
(2007/10/03)
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- Propargyloxycarbonyl (Poc) amino acid chlorides as efficient coupling reagents for the synthesis of 100% diastereopure peptides and resin bound tetrathiomolybdate as an effective deblocking agent for the Poc group
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Synthesis of short peptides using propargyloxycarbonyl amino acid chlorides as effective coupling reagents and polymer supported tetrathiomolybdate as an efficient deblocking agent are reported.
- Bhat, Ramakrishna G.,Sinha, Surajit,Chandrasekaran, Srinivasan
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p. 812 - 813
(2007/10/03)
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- Highly efficient and enantioselective synthesis of L-arylglycines and D-arylglycine amides from biotransformations of nitriles
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Under very mild conditions, the Rhodococcus sp. AJ270-catalysed biotransformation of arylglycine nitriles 1, prepared easily from the reaction of substituted benzaldehydes, ammonium chloride and potassium cyanide, proceeded efficiently to produce optically active D-arylglycine amides 2 and L-arylglycines 3 in excellent yields with enantiomeric excesses higher than 99%.
- Wang, Mei-Xiang,Lin, Shuang-Jun
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p. 6925 - 6927
(2007/10/03)
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