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Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.
Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
supporting information
p. 390 - 398
(2021/01/13)

Investigation of Taniaphos as a chiral selector in chiral extraction of amino acid enantiomers
Finding chiral selector with high stereoselectivity to a variety of amino acid enantiomers remains a challenge and warrants further research. In this work, Taniaphos, a chiral ligand with rotatable spatial configuration, was employed as a chiral extractant to enantioseparate various amino acid enantiomers. Phenylalanine (Phe), homophenylalanine (Hphe), 4-nitrophenylalanine (Nphe), and 3-chloro-phenylglycine (Cpheg) were used as substrates to evaluate the extraction efficiency. The results revealed that Taniaphos-Cu exhibited good abilities to enantioseparate Phe, Hphe, Nphe, and Cpheg with the highest separation factors (α) of 3.13, 2.10, 2.32, and 2.14, respectively. Taniaphos-Cu is more conducive to combine with D-amino acid in extraction. The influences of pH, Taniaphos-Cu, and concentration and extraction temperature on extraction were comprehensively evaluated. The highest performance factors (pf) for Phe, Hphe, Nphe, and Cpheg at optimal extraction conditions were 0.08892, 0.1250, 0.09621, and 0.08021, respectively. The recognition mechanism between Taniaphos-Cu and amino acid enantiomers was discussed. The coordination interaction between Taniaphos-Cu and -COO?, π-π interaction between Taniaphos-Cu and amino acid enantiomers are important acting forces in chiral extraction. The steric-hindrance between -NH2 and -OH lead to Taniaphos-Cu-D-Phe is more stable than Taniaphos-Cu-L-Phe. This work provided a chiral extractant that has good abilities to enantioseparate various amino acid enantiomers.
Xiao, Wenjie,Chen, Shuhuan,Liu, Xiong,Ma, Yu
p. 292 - 302
(2021/03/29)

Reconstruction of Hyper-Thermostable Ancestral L-Amino Acid Oxidase to Perform Deracemization to D-Amino Acids
L-amino acid oxidases (LAAOs) with broad substrate specificity can be used in the deracemization of D,L-amino acids (D,L-AAs) to their D-enantiomers. Hyper-thermostable LAAO (HTAncLAAO) was designed through a combination of manual sequence data mining and ancestral sequence reconstruction. Soluble expression of HTAncLAAO (>50 mg/L) can be achieved using an E. coli system. HTAncLAAO, which recognizes seven L-AAs as substrates, exhibits extremely high thermal stability and long-term stability; the t1/2 value was 95 °C and 99 % ee, D-enantiomer). These results suggest that HTAncLAAO is an excellent biocatalyst to perform this deracemization.
Ishida, Chiharu,Miyata, Ryo,Hasebe, Fumihito,Miyata, Azusa,Kumazawa, Shigenori,Ito, Sohei,Nakano, Shogo
p. 5228 - 5235
(2021/11/05)

Efficient Synthesis of D-Phenylalanine from L-Phenylalanine via a Tri-Enzymatic Cascade Pathway
D-phenylalanine is an important intermediate in food and pharmaceutical industries. Here, to enable efficient D-phenylalanine biosynthesis from L-phenylalanine, a tri-enzymatic cascade was designed and reconstructed in vivo. The activity of Proteus vulgaris meso-diaminopimelate dehydrogenase (PvDAPDH) toward phenyl pyruvic acid was identified as the limiting step. To overcome, the tension in the phenyl pyruvic acid side-chain, PvDAPDH was engineered, generating PvDAPDHW121A/R181S/H227I, whose catalytic activity of 6.86 U mg?1 represented an 85-fold increase over PvDAPDH. Introduction of PvDAPDHW121A/R181S/H227I, P. mirabilis L-amino acid deaminase, and Bacillus megaterium glucose dehydrogenase in E. coli enabled the production of 57.8 g L?1 D-phenylalanine in 30 h, the highest titer to date using 60 g L?1 L-phenylalanine as starting substrate, which meant a 96.3 % conversion rate and >99 % enantioselectivity on a 3-L scale. The proposed tri-enzymatic cascade provides a novel potential bio-based approach for industrial production of D-phenylalanine from cheap amino acids.
Lu, Cui,Zhang, Sheng,Song, Wei,Liu, Jia,Chen, Xiulai,Liu, Liming,Wu, Jing
p. 3165 - 3173
(2021/06/09)

Protein Engineering of d-Succinylase from Cupriavidus sp. for d-Amino Acid Synthesis and the Structural Implications
d-Amino acids are important chiral building blocks for pharmaceuticals and agrochemicals. Previously, we have used d-Succinylase (DSA) from Cupriavidus sp. P4-10-C and N-succinyl amino acid racemase (NSAR, EC.4.2.1.113) from Geobacillus stearothermophilus NCA1503 to produce d-amino acids via the dynamic kinetic resolution of N-succinyl-dl-amino acids. However, the use of this bioconversion system remains challenging for industrial application due to the insufficient enantioselectivity of DSA toward N-succinyl-d-amino acids. Therefore, we screened DSA mutants for improved enantioselectivity by directed evolution. Several mutants showed improved enantioseletivity compared to wild-type DSA. L182E mutant had superior enantioselectivity, and the thermal stability was also remarkably improved by this single mutation. We solved the crystal structure of the L182E mutant in complex with succinic acids at a resolution 2.0 ?. The mutated residues in all generated mutants that showed improved enantioselectivity (including the substituted Glu182 in the L182E mutant) are found very close to the active site. The solved crystal structure also provides some rationale to explain the higher thermostability of the L182E mutant compared to wild-type DSA. d-phenylalanine and d-tryptophan were produced in high conversion (approximately 90%) with 98.8% ee and 99.6% ee, respectively, using coupled L182E DSA and NSAR with the one-pot enzymatic method. These data suggested that L182E DSA may be a useful biocatalyst for industrial d-amino acids production. (Figure presented.).
Azuma, Masayuki,Kumagai, Shinya,Nishiya, Yoshiaki,Sumida, Yosuke,Yamada, Toshihide,Yamasaki, Masayuki
p. 4770 - 4778
(2021/08/30)

Adiponectin-Secretion-Promoting Cyclic Peptide-Polyketide Hybrids from a Halophyte-Associated Fungus, Colletotrichum gloeosporioides JS0417
Three new cyclic peptide-polyketide hybrids (1-3) and two new chaetiacandin-type polyketides (4 and 5) along with nine known compounds were isolated from cultures of a halophyte-associated fungus, Colletotrichum gloeosporioides JS0417. Spectroscopic analysis revealed that 1-3 were cyclic depsipeptides where 3,5,11-trihydroxy-2,6-dimethyldodecanoic acid was linked to two amino acids through amide and ester bonds to form a 12-membered ring. Relative and absolute configurations for the peptides were determined with spectroscopic analysis and chemical reactions. The cyclic depsipeptides 2 and 6 were determined to act as strong adiponectin-secretion-promoting modulators with potential to treat metabolic diseases associated with hypoadiponectinemia. Notably, a known compound, tryptophol, significantly inhibited PGE2synthesis and also promoted adiponectin secretion, exhibiting a similar biological activity profile to aspirin, but with greater potency. The presence of an isoleucine moiety and non-glycosylation may be important for biological activity of the cyclic peptide-polyketide hybrids, and non-methoxylation of the side chain may influence activity of the indole derivatives.
An, Seungchan,Bang, Sunghee,Deyrup, Stephen T.,Gong, Junpyo,Kim, Jaekyeong,Ko, Hyejin,Lee, Changyeol,Noh, Minsoo,Shim, Sang Hee
(2022/03/02)

Simultaneous Preparation of (S)-2-Aminobutane and d -Alanine or d -Homoalanine via Biocatalytic Transamination at High Substrate Concentration
(S)-2-Aminobutane, d-alanine, and d-homoalanine are important intermediates for the production of various active pharmaceutical ingredients and food additives. The preparation of these small chiral amine or amino acids with high water solubility still demands searching for efficient methods. In this work, we identified an ω-transaminase (ω-TA) from Sinirhodobacter hungdaonensis (ShdTA) that catalyzed the kinetic resolution of racemic 2-aminobutane at a concentration of 800 mM using pyruvate as the amino acceptor, leading to the simultaneous isolation of enantiopure (S)-2-aminobutane and d-alanine in 46% and 90% yield, respectively. In addition, (S)-2-aminobutane (98% ee) and d-homoalanine (99% ee) were isolated in 45% and 93% yield, respectively, in the kinetic resolution of racemic 2-aminobutane at a concentration of 400 mM coupled with deamination of l-threonine by threonine deaminase. We thus developed a biocatalytic process for the practical synthesis of these valuable small chiral amine and d-amino acids.
Li, Jianjiong,Wang, Yingang,Wu, Qiaqing,Yao, Peiyuan,Yu, Shanshan,Zhu, Dunming
supporting information

(2022/03/01)

Asymmetric Reduction of Aromatic α-Dehydroamino Acid Esters with Water as Hydrogen Source
The asymmetric reduction of aromatic α-dehydroamino acid esters with water as the hydrogen source was developed by a Rh/Cu co-catalytic system. The reaction tolerates various functional groups, providing a valuable synthetic tool to access chiral α-amino acid esters readily. Moreover, the present methodology also was applied in the cost-effective and easy to handle preparation of chiral deuterated α-amino esters by using D2O.
Dai, Yuze,Chen, Jingchao,Wang, Zheting,Wang, Ting,Wang, Lin,Yang, Yong,Qiao, Xingfang,Fan, Baomin
p. 7141 - 7147
(2021/05/29)

A novel phenylalanine ammonia-lyase from Pseudozyma antarctica for stereoselective biotransformations of unnatural amino acids
A novel phenylalanine ammonia-lyase of the psychrophilic yeast Pseudozyma antarctica (PzaPAL) was identified by screening microbial genomes against known PAL sequences. PzaPAL has a significantly different substrate binding pocket with an extended loop (26 aa long) connected to the aromatic ring binding region of the active site as compared to the known PALs from eukaryotes. The general properties of recombinant PzaPAL expressed in E. coli were characterized including kinetic features of this novel PAL with L-phenylalanine (S)-1a and further racemic substituted phenylalanines rac-1b-g,k. In most cases, PzaPAL revealed significantly higher turnover numbers than the PAL from Petroselinum crispum (PcPAL). Finally, the biocatalytic performance of PzaPAL and PcPAL was compared in the kinetic resolutions of racemic phenylalanine derivatives (rac-1a-s) by enzymatic ammonia elimination and also in the enantiotope selective ammonia addition reactions to cinnamic acid derivatives (2a-s). The enantiotope selectivity of PzaPAL with o-, m-, p-fluoro-, o-, p-chloro- and o-, m-bromo-substituted cinnamic acids proved to be higher than that of PcPAL.
Varga, Andrea,Csuka, Pál,Sonesouphap, Orlavanah,Bánóczi, Gergely,To?a, Monica Ioana,Katona, Gabriel,Molnár, Zsófia,Bencze, László Csaba,Poppe, László,Paizs, Csaba
p. 185 - 194
(2020/04/28)

Hydrogen Bond Assisted l to d Conversion of α-Amino Acids
l to d conversion of unactivated α-amino acids was achieved by solubility-induced diastereomer transformation (SIDT). Ternary complexes of an α-amino acid with 3,5-dichlorosalicylaldehyde and a chiral guanidine (derived from corresponding chiral vicinal diamine) were obtained in good yield as diastereomerically pure imino acid salt complexes and were hydrolysed to obtain enantiopure α-amino acids. A combination of DFT computation, NMR spectroscopy, and crystal structure provide detailed insight into how two types of strong hydrogen bonds assist in rapid epimerization of the complexes that is essential for SIDT.
Chin, Jik,Fu, Rui,Lough, Alan J.,So, Soon Mog
p. 4335 - 4339
(2020/02/11)

Exploration of Transaminase Diversity for the Oxidative Conversion of Natural Amino Acids into 2-Ketoacids and High-Value Chemicals
The use of 2-ketoacids is very common in feeds, food additives, and pharmaceuticals, and 2-ketoacids are valuable precursors for a plethora of chemically diverse compounds. Biocatalytic synthesis of 2-ketoacids starting from l-amino acids would be highly desirable because the substrates are readily available from biomass feedstock. Here, we report bioinformatic exploration of a series of aminotransferases (ATs) to achieve the desired conversion. Thermodynamic control was achieved by coupling an l-glutamate oxidation reaction in the cascade for the recycling of the amine acceptor. These enzymes were able to convert a majority of proteinogenic amino acids into the corresponding 2-ketoacids with high conversion (up to 99percent) and atom-efficiency. Furthermore, this enzyme cascade was extendable, and one-pot two-step processes were established for the synthesis of d-amino acids and N-methylated amino acids, achieving great overall conversion (up to 99percent) and high ee values (>99percent). These developed enzymatic methodologies offer convenient routes for utilizing amino acids as synthetic reagents.
Chen, Yanchun,Cui, Xuexian,Cui, Yinglu,Li, Chuijian,Li, Ruifeng,Li, Tao,Sun, Jinyuan,Wu, Bian,Zhu, Tong
p. 7950 - 7957
(2020/08/21)

D-Phenylglycine aminotransferase (d-PhgAT)-substrate scope and structural insights of a stereo-inverting biocatalyst used in the preparation of aromatic amino acids
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
p. 6533 - 6543
(2020/11/13)

Iheyamides A-C, Antitrypanosomal Linear Peptides Isolated from a Marine Dapis sp. Cyanobacterium
Iheyamides A (1), B (2), and C (3), new linear peptides, were isolated from a marine Dapis sp. cyanobacterium. Their structures were elucidated by spectroscopic analyses and degradation reactions. Iheyamide A (1) showed moderate antitrypanosomal activities against Trypanosoma brucei rhodesiense and Trypanosoma brucei brucei (IC50 = 1.5 μM), but the other two analogues, iheyamides B (2) and C (3), did not (IC50 > 20 μM, respectively). The structure-activity relationship clarified that an isopropyl-O-Me-pyrrolinone moiety was necessary for the antitrypanosomal activity. Furthermore, the cytotoxicity of 1 against normal human cells, WI-38, was 10 times weaker than its antitrypanosomal activity (IC50 = 18 μM).
Kurisawa, Naoaki,Iwasaki, Arihiro,Jeelani, Ghulam,Nozaki, Tomoyoshi,Suenaga, Kiyotake
p. 1684 - 1690
(2020/06/08)

Characterization of diketopiperazine heterodimers as potential chemical markers for discrimination of two dominant black aspergilli, Aspergillus niger and Aspergillus tubingensis
Black aspergilli are distributed worldwide and represent one of the most prolific sources of metabolites with biomedical and agrochemical interests. However, due to their similar morphological characteristics and insufficient molecular identification, the taxonomic classification of black aspergilli remains ill-defined. The production of specialised metabolites is often unique for species among black aspergilli and could be used as diagnostic chemical markers for species identification. In this study, chemical investigation of Aspergillus tubingensis OUCMBIII 143291 led to the discovery of the diagnostic chemical marker asperazine, a complex diketopiperazine heterodimer, as well as two previously undescribed analogues, asperazine B and C. In addition, an undescribed 2-benzylpyridin-4(1H)-one-containing amide, pestalamide D, along with four known related metabolites were isolated. Their chemical structures, including their absolute configurations, were established on the basis of comprehensive spectral analysis and chiral HPLC analysis of the acidic hydrolysates. Asperazines B and C can serve as potential chemical markers for distinguishing A. tubingensis from A. niger, two representative species of black aspergilli that are usually incorrectly identified. Moreover, the isolated compounds were evaluated for their antifungal activity against eight phytopathogenic fungi including Alternaria alternata, A. brassicae, Botrytis cinerea, Colletotrichum lagenarium, Fusarium oxysporum, Gaeumannomyces graminis, Penicillium digitatum, and Valsa mali. Pestalamide D exhibited significant activities against B. cinerea, C. lagenarium, and V. mali, with MIC values of 4, 8, and 8 μg/mL, respectively, compared with the positive controls carbendazim (MICs = 8, 4, and 4 μg/mL) and prochloraz (MICs = 8, 8, and 4 μg/mL). The results of this study reveal two additional chemical markers and provide a powerful tool for the rapid identification of black aspergilli.
Deng, Ning,Li, Wei,Ren, Guang-Wei,Wang, Xiao-Qiang,Wang, Xiu-Fang,Xu, Ce,Xu, Kuo,Yuan, Xiao-Long,Zhang, Peng
(2020/05/13)

Pagoamide A, a Cyclic Depsipeptide Isolated from a Cultured Marine Chlorophyte, Derbesia sp., Using MS/MS-Based Molecular Networking
A thiazole-containing cyclic depsipeptide with 11 amino acid residues, named pagoamide A (1), was isolated from laboratory cultures of a marine Chlorophyte, Derbesia sp. This green algal sample was collected from America Samoa, and pagoamide A was isolated using guidance by MS/MS-based molecular networking. Cultures were grown in a light- and temperature-controlled environment and harvested after several months of growth. The planar structure of pagoamide A (1) was characterized by detailed 1D and 2D NMR experiments along with MS and UV analysis. The absolute configurations of its amino acid residues were determined by advanced Marfey's analysis following chemical hydrolysis and hydrazinolysis reactions. Two of the residues in pagoamide A (1), phenylalanine and serine, each occurred twice in the molecule, once in the d- and once in the l-configuration. The biosynthetic origin of pagoamide A (1) was considered in light of other natural products investigations with coenocytic green algae.
Cottrell, Garrison W.,Fang, Fang,Gerwick, Lena,Gerwick, William H.,Glukhov, Evgenia,Guan, Huashi,Kim, Hyunwoo,Leao, Tiago,Li, Yueying,Mao, Huanru Henry,Murray, Thomas F.,Pierce, Marsha L.,Yu, Hao-Bing,Zhang, Chen,Zhang, Yi
supporting information

(2020/01/31)

Preparation and characterization of a new open-tubular capillary column for enantioseparation by capillary electrochromatography
In order to use the enantioseparation capability of cationic cyclodextrin and to combine the advantages of capillary electrochromatography (CEC) with open-tubular (OT) column, in this study, a new OT-CEC, coated with cationic cyclodextrin (1-allylimidazolium-β-cyclodextrin [AI-β-CD]) as chiral stationary phase (CSP), was prepared and applied for enantioseparation. Synthesized AI-β-CD was characterized by infrared (IR) spectrometry and mass spectrometry (MS). The preparation conditions for the AI-β-CD-coated column were optimized with the orthogonal experiment design L9(34). The column prepared was characterized by scanning electron microscopy (SEM) and elemental analysis (EA). The results showed that the thickness of stationary phase in the inner surface of the AI-β-CD-coated columns was about 0.2 to 0.5?μm. The AI-β-CD content in stationary phase based on the EA was approximately 2.77?mmol·m?2. The AI-β-CD-coated columns could separate all 14 chiral compounds (histidine, lysine, arginine, glutamate, aspartic acid, cysteine, serine, valine, isoleucine, phenylalanine, salbutamol, atenolol, ibuprofen, and napropamide) successfully in the study and exhibit excellent reproducibility and stability. We propose that the column, coated with AI-β-CD, has a great potential for enantioseparation in OT-CEC.
Li, Yingjie,Tang, Yimin,Qin, Shili,Li, Xue,Dai, Qiang,Gao, Lidi
p. 283 - 292
(2019/02/05)

Highly selective synthesis of d-amino acids from readily available l-amino acids by a one-pot biocatalytic stereoinversion cascade
d-Amino acids are key intermediates required for the synthesis of important pharmaceuticals. However, establishing a universal enzymatic method for the general synthesis of d-amino acids from cheap and readily available precursors with few by-products is challenging. In this study, we constructed and optimized a cascade enzymatic route involving l-amino acid deaminase and d-amino acid dehydrogenase for the biocatalytic stereoinversions of l-amino acids into d-amino acids. Using l-phenylalanine (l-Phe) as a model substrate, this artificial biocatalytic cascade stereoinversion route first deaminates l-Phe to phenylpyruvic acid (PPA) through catalysis involving recombinant Escherichia coli cells that express l-amino acid deaminase from Proteus mirabilis (PmLAAD), followed by stereoselective reductive amination with recombinant meso-diaminopimelate dehydrogenase from Symbiobacterium thermophilum (StDAPDH) to produce d-phenylalanine (d-Phe). By incorporating a formate dehydrogenase-based NADPH-recycling system, d-Phe was obtained in quantitative yield with an enantiomeric excess greater than 99%. In addition, the cascade reaction system was also used to stereoinvert a variety of aromatic and aliphatic l-amino acids to the corresponding d-amino acids by combining the PmLAAD whole-cell biocatalyst with the StDAPDH variant. Hence, this method represents a concise and efficient route for the asymmetric synthesis of d-amino acids from the corresponding l-amino acids.
Zhang, Danping,Jing, Xiaoran,Zhang, Wenli,Nie, Yao,Xu, Yan
p. 29927 - 29935
(2019/10/01)

An Ugi-like Biosynthetic Pathway Encodes Bombesin Receptor Subtype-3 Agonists
Isocyanide functional groups can be found in a variety of natural products. Rhabduscin is one such isocyanide-functionalized immunosuppressant produced in Xenorhabdus and Photorhabdus gammaproteobacterial pathogens, and deletion of its biosynthetic gene cluster inhibits virulence in an invertebrate animal infection model. Here, we characterized the first "opine-glycopeptide" class of natural products termed rhabdoplanins, and strikingly, these molecules are spontaneously produced from rhabduscin via an unprecedented multicomponent "Ugi-like" reaction sequence in nature. The rhabdoplanins also represent new lead G protein-coupled receptor (GPCR) agonists, stimulating the bombesin receptor subtype-3 (BB3) GPCR.
Oh, Joonseok,Kim, Nam Y.,Chen, Haiwei,Palm, Noah W.,Crawford, Jason M.
p. 16271 - 16278
(2019/11/02)

Deracemization and stereoinversion to aromatic d-amino acid derivatives with ancestral l-amino acid oxidase
Enantiomerically pure amino acid derivatives could be foundational compounds for peptide drugs. Deracemization of racemates to l-amino acid derivatives can be achieved through the reaction of evolved d-amino acid oxidase and chemical reductants, whereas deracemization to d-amino acid derivatives has not progressed due to the difficulty associated with the heterologous expression of l-amino acid oxidase (LAAO). In this study, we succeeded in developing an ancestral LAAO (AncLAAO) bearing broad substrate selectivity (13 l-amino acids) and high productivity through an Escherichia coli expression system (50.7 mg/L). AncLAAO can be applied to perform deracemization to d-amino acids in a similar way to deracemization to l-amino acids. In fact, full conversion (>99% ee, d-form) could be achieved for 16 racemates, including nine d,l-Phe derivatives, six d,l-Trp derivatives, and a d,l-phenylglycine. Taken together, we believe that AncLAAO could be a key enzyme to obtain optically pure d-amino acid derivatives in the future.
Nakano, Shogo,Minamino, Yuki,Hasebe, Fumihito,Ito, Sohei
p. 10152 - 10158
(2019/10/19)

"Fishing and hunting"-selective immobilization of a recombinant phenylalanine ammonia-lyase from fermentation media
This article overviews the numerous immobilization methods available for various biocatalysts such as whole-cells, cell fragments, lysates or enzymes which do not require preliminary enzyme purification and introduces an advanced approach avoiding the costly and time consuming downstream processes required by immobilization of purified enzyme-based biocatalysts (such as enzyme purification by chromatographic methods and dialysis). Our approach is based on silica shell coated magnetic nanoparticles as solid carriers decorated with mixed functions having either coordinative binding ability (a metal ion complexed by a chelator anchored to the surface) or covalent bond-forming ability (an epoxide attached to the surface via a proper linker) enabling a single operation enrichment and immobilization of a recombinant phenylalanine ammonia-lyase from parsley fused to a polyhistidine affinity tag.
Sánta-Bell, Evelin,Molnár, Zsófia,Varga, Andrea,Nagy, Flóra,Hornyánszky, Gábor,Paizs, Csaba,Balogh-Weiser, Diána,Poppe, László
supporting information

(2019/11/28)

Artificial Biocatalytic Cascade with Three Enzymes in One Pot for Asymmetric Synthesis of Chiral Unnatural Amino Acids
Two biocatalytic reactions, transamination catalyzed by transaminases and reductive amination catalyzed by amino acid dehydrogenases, can be used for asymmetric synthesis of optically pure unnatural amino acids. However, although transaminases show a great diversity and broad substrate spectrum, most transaminase reactions are reversible, while amino acid dehydrogenases catalyze reductive amination irreversibly but with strict substrate specificity. Accordingly, herein we developed a tri-enzyme one-pot reaction system to exploit the respective advantages of transaminases and amino acid dehydrogenases, while overcoming the disadvantages of each. In this work, representatives of all four subgroups of transaminases coupled with different amino acid dehydrogenases to produce five l- and four d- unnatural amino acid products, using ammonia and the co-enzyme NAD(P)H, which is regenerated by a robust alcohol dehydrogenase with 2-propanol as cheap cosubstrate. The complete conversion and high enantiopurity (ee > 99 %) of the products, demonstrated it as an ideal alternative for asymmetric synthesis of chiral amino acid compounds.
Zhou, Haisheng,Meng, Lijun,Yin, Xinjian,Liu, Yayun,Xu, Gang,Wu, Jianping,Wu, Mianbin,Yang, Lirong
supporting information
p. 6470 - 6477
(2019/11/02)

Molecularly imprinted polymer as stationary phase for HPLC separation of phenylalanine enantiomers
Abstract: l-Phenylalanine molecularly imprinted polymers were synthesized by bulk polymerization. Methacrylic acid and acrylamide were tested as functional monomers. Ethanol and acetonitrile were used as porogenic solvents. Optimal composition of polymerization mixture was methacrylic acid, template, and ethylene glycol dimethacrylate in molar ratio 1:5:26. MIP was applied as HPLC chiral stationary phase. The influences of the mobile phase composition, flow rate, column temperature, and column length on the efficiency of enantioseparation were investigated. The enantioselective separation of phenylalanine was attained in reversed phase mode at 45?°C with acetonitrile/water containing 1.5% acetic acid (90/10, v/v) as mobile phase (resolution value was 1.49, selectivity factor was 1.38). Applicability of polymeric stationary phase prepared for l-phenylalanine was tested for analysis of dietary supplement sample. The UV detection limits for both enantiomers were 1?mg?cm?3 (S/N?=?3). Good linearity was observed from 1 to 10?mg?cm?3.
Hroboňová, Katarína,Lomenova, Anna
p. 939 - 946
(2018/02/21)

Evaluation of the Edman degradation product of vancomycin bonded to core-shell particles as a new HPLC chiral stationary phase
A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.
Hellinghausen, Garrett,Lopez, Diego A.,Lee, Jauh T.,Wang, Yadi,Weatherly, Choyce A.,Portillo, Abiud E.,Berthod, Alain,Armstrong, Daniel W.
p. 1067 - 1078
(2018/08/01)

Complex-precipitation using functionalized chiral ionic liquids with L-proline anion and chromatographic analysis for enantioseparation of racemic amino acids
As one kind of functionalized green medium, chiral ionic liquids (CILs) have been widely applied in fields of asymmetric catalysis, enantioseparation, and so on. In this study, four kinds of amino acid–based CILs were synthesized by using trimethylamine, N-methylpyrrolidine, N-methylimidazole, and tropine as cationic nucleus, respectively. Then their specific optical rotation and solubility in common solvents were determined for further resolution application. The effect of different cations in these CILs was explored on the separation of racemic phenylalanine in complex-precipitation way. Moreover, various factors were systematically investigated for their effects on resolution efficiency, including the type of additive copper salts, the molar ratio of Cu (II) to CIL, pH value, the amount of racemic phenylalanine, and temperature. Under the appropriate conditions, L-phenylalanine mainly existed in solid phase and could be separated from its enantiomers in liquid phase. Furthermore, the mechanism of resolution was studied by thermogravimetric analysis, infrared spectrum, and molecular simulation. The resolution system has characteristics of no organic solvent, fast separation speed, simple resolution process, and easy scale-up.
Zang, Huimin,Yao, Shun,Luo, Yingjie,Tang, Dan,Song, Hang
p. 1182 - 1194
(2018/09/12)

Engineered Aminotransferase for the Production of d-Phenylalanine Derivatives Using Biocatalytic Cascades
d-Phenylalanine derivatives are valuable chiral building blocks for a wide range of pharmaceuticals. Here, we developed stereoinversion and deracemization biocatalytic cascades to synthesize d-phenylalanine derivatives that contain electron-donating or -withdrawing substituents of various sizes and at different positions on the phenyl ring with a high enantiomeric excess (90 to >99 % ee) from commercially available racemic mixtures or l-amino acids. These whole-cell systems couple Proteus mirabilis l-amino acid deaminase with an engineered aminotransferase that displays native-like activity towards d-phenylalanine, which we generated from Bacillus sp. YM-1 d-amino acid aminotransferase. Our cascades are applicable to preparative-scale synthesis and do not require cofactor-regeneration systems or chemical reducing agents.
Walton, Curtis J. W.,Parmeggiani, Fabio,Barber, Janet E. B.,McCann, Jenna L.,Turner, Nicholas J.,Chica, Roberto A.
p. 470 - 474
(2017/12/15)

Structure-guided engineering of: Meso -diaminopimelate dehydrogenase for enantioselective reductive amination of sterically bulky 2-keto acids
meso-Diaminopimelate dehydrogenase (DAPDH) and mutant enzymes are an excellent choice of biocatalysts for the conversion of 2-keto acids to the corresponding d-amino acids. However, their application in the enantioselective reductive amination of bulky 2-keto acids, such as phenylglyoxylic acid, 2-oxo-4-phenylbutyric acid, and indole-3-pyruvic acid, is still challenging. In this study, the structure-guided site-saturation mutagenesis of a Symbiobacterium thermophilum DAPDH (StDAPDH) gave rise to a double-site mutant W121L/H227I, which showed dramatically improved enzyme activities towards various 2-keto acids including these sterically bulky substrates. Several d-amino acids were prepared in optically pure form. The molecular docking of substrates into the active sites of wild-type and mutant W121L/H227I enzymes revealed that the substrate binding cavity of the mutant enzyme was reshaped to accommodate these bulky substrates, thus leading to higher enzyme activity. These results lay a foundation for further shaping the substrate binding pocket and manipulating the interactions between the substrate and binding sites to access highly active d-amino acid dehydrogenases for the preparation of synthetically challenging d-amino acids.
Cheng, Xinkuan,Chen, Xi,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
p. 4994 - 5002
(2018/10/17)

One-Pot Enzymatic Synthesis of d-Arylalanines Using Phenylalanine Ammonia Lyase and l-Amino Acid Deaminase
The phenylalanine ammonia-lyase (AvPAL) from Anabaena variabilis catalyzes the amination of substituent trans-cinnamic acid (t-CA) to produce racemic d,l-enantiomer arylalanine mixture owing to its low stereoselectivity. To produce high optically pure d-arylalanine, a modified AvPAL with high d-selectivity is expected. Based on the analyses of catalytic mechanism and structure, the Asn347 residue in the active site was proposed to control stereoselectivity. Therefore, Asn347 was mutated to construct mutant AvPAL-N347A, the stereoselectivity of AvPAL-N347A for d-enantiomer arylalanine was 2.3-fold higher than that of wild-type AvPAL (WtPAL). Furthermore, the residual l-enantiomer product in reaction solution could be converted into the d-enantiomer product through stereoselective oxidation by PmLAAD and nonselective reduction by reducing agent NH3BH3. At optimal conditions, the conversion rate of t-CA and optical purity (enantiomeric excess (eeD)) of d-phenylalanine reached 82% and exceeded 99%, respectively. The two enzymes displayed activity toward a broad range of substrate and could be used to efficiently synthesize d-arylalanine with different groups on the phenyl ring. Among these d-arylalanines, the yield of m-nitro-d-phenylalanine was highest and reached 96%, and the eeD exceeded 99%. This one-pot synthesis using AvPAL and PmLAAD has prospects for industrial application.
Zhu, Longbao,Feng, Guoqiang,Ge, Fei,Song, Ping,Wang, Taotao,Liu, Yi,Tao, Yugui,Zhou, Zhemin
p. 1 - 15
(2018/06/11)

Discovery of new A- and B-type laxaphycins with synergistic anticancer activity
Two new cyclic lipopeptides termed laxaphycins B4 (1) and A2 (2) were discovered from a collection of the marine cyanobacterium Hormothamnion enteromorphoides, along with the known compound laxaphycin A. The planar structures were solved based on a combined interpretation of 1D and 2D NMR data and mass spectral data. The absolute configurations of the subunits were determined by chiral LC-MS analysis of the hydrolysates, advanced Marfey's analysis and 1D and 2D ROESY experiments. Consistent with similar findings on other laxaphycin A- and B-type peptides, laxaphycin B4 (1) showed antiproliferative effects against human colon cancer HCT116 cells with IC50 of 1.7 μM, while laxaphycins A and A2 (2) exhibited weak activities. The two major compounds isolated from the sample, laxaphycins A and B4, were shown to act synergistically to inhibit the growth of HCT116 colorectal cancer cells.
Cai, Weijing,Matthew, Susan,Chen, Qi-Yin,Paul, Valerie J.,Luesch, Hendrik
p. 2310 - 2319
(2018/04/02)

Streptopyrazinones A?D, rare metabolites from marine-derived Streptomyces sp. ZZ446
Secondary metabolites from marine-associated actinomycetes are important source for the discovery of novel bioactive compounds. In this study, an actinomycete Streptomyces sp. ZZ446 was isolated from coastal soils and different media were used to culture this isolated marine actinomycete. It has been found that this actinomycete in the liquid medium of 2216 E with sea salt produced five new compounds of streptopyrazinones A?D (1–4) and N-acetyl-L-isoleucine-L-leucinamide (5) as well as six known diketopiperazines (6–11) and one alkaloid (12). Structures of the new compounds were determined by extensive NMR analyses, HRESIMS data, electronic circular dichroism (ECD) calculation, chemical degradation, Marfey's method, and X-ray diffraction analysis. This type of streptopyrazinones A?D (1–4) is rarely found in the natural resources. New compounds 1–5 showed activity in inhibiting the growth of Candida albicans and methicillin-resistant Staphylococcus aureus.
Chen, Mengxuan,Chai, Weiyun,Zhu, Rongyao,Song, Tengfei,Zhang, Zhizhen,Lian, Xiao-Yuan
supporting information
p. 2100 - 2106
(2018/03/26)

Chromatographic Resolution of α-Amino Acids by (R)-(3,3'-Halogen Substituted-1,1'-binaphthyl)-20-crown-6 Stationary Phase in HPLC
Three new chiral stationary phases (CSPs) for high-performance liquid chromatography were prepared from R-(3,3'-halogen substituted-1,1'-binaphthyl)-20-crown-6 (halogen = Cl, Br and I). The experimental results showed that R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 (CSP-1) possesses more prominent enantioselectivity than the two other halogen-substituted crown ether derivatives. All twenty-one α-amino acids have different degrees of separation on R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6-based CSP-1 at room temperature. The enantioselectivity of CSP-1 is also better than those of some commercial R-(1,1'-binaphthyl)-20-crown-6 derivatives. Both the separation factors (α) and the resolution (Rs) are better than those of commercial crown ether-based CSPs [CROWNPAK CR(+) from Daicel] under the same conditions for asparagine, threonine, proline, arginine, serine, histidine and valine, which cannot be separated by commercial CR(+). This study proves the commercial usefulness of the R-(3,3'-dibromo-1,1'-binaphthyl)-20-crown-6 chiral stationary phase.
Wu, Peng,Wu, Yuping,Zhang, Junhui,Lu, Zhenyu,Zhang, Mei,Chen, Xuexian,Yuan, Liming
supporting information
p. 1037 - 1042
(2017/07/25)

Bio-inspired enantioselective full transamination using readily available cyclodextrin
The mimics of vitamin B6-dependent enzymes that catalyzed an enantioselective full transamination in the pure aqueous phase have been realized for the first time through the establishment of a new “pyridoxal 5′-phosphate (PLP) catalyzed non-covalent cyclodextrin (CD)-keto acid inclusion complexes” system, and various optically active amino acids have been obtained.
Zhang, Shiqi,Li, Guangxun,Liu, Hongxin,Wang, Yingwei,Cao, Yuan,Zhao, Gang,Tang, Zhuo
p. 4203 - 4208
(2017/02/05)

Thermo-responsive adsorption and separation of amino acid enantiomers using smart polymer-brush-modified magnetic nanoparticles
Multifunctional magnetic nanoparticles simultaneously possessing thermo-responsive properties and chiral recognition ability show great potential in enantiomeric separation. In this study, a novel type of multifunctional magnetic Fe3O4 nanoparticle, decorated with smart polymer brushes consisting of poly(N-isopropylacrylamide-co-glycidyl methacrylate) chains with pendent β-cyclodextrin (β-CD) units, was fabricated as a chiral nanoselector for the thermo-sensitive selective adsorption and separation of three amino acid enantiomers. These smart polymer brushes were grafted on the surface of Fe3O4 nanoparticles via a combination of surface-initiated atom transfer radical polymerization and ring-opening reaction. The pendent β-CD units can serve as smart receptors for selectively recognizing enantiomeric molecules via formation of stable host-guest inclusion complexes. The thermo-sensitive poly(N-isopropylacrylamide) chains can act as microenvironmental adjustors for tuning the inclusion constants of β-CD toward enantiomeric guest molecules. The prepared multifunctional magnetic nanoparticles exhibit excellent thermo-responsive adsorption and decomplexation performances toward amino acid enantiomers. Via simply changing the operation temperature, the decomplexation of amino acid enantiomers and regeneration of the smart chiral magnetic nanoparticles can be easily achieved. Besides, the magnetic properties of the regenerated smart nanoparticles enable easy recovery under an external magnetic field for reuse. Such multifunctional magnetic nanoparticles with highly chiral recognition capability, excellent thermo-sensitive adsorption and decomplexation properties toward amino acid enantiomers, and recyclability show great potential in chiral separations.
Song, Ya-Ya,Song, Xiao-Dong,Yuan, Heng,Cheng, Chang-Jing
p. 3194 - 3207
(2016/05/09)

A reaction-extraction separation phenylalanie antimer of the new method
The invention discloses a new method for separation of phenylalanine enantiomer by reaction extraction, which uses (S)-BINAP-copper complex as chiral extractant in the organic phase to extract and separate phenylalanine enantiomer from the water phase. The invention discloses a preparation method for (S)-BINAP-copper complex. (S)-BINAP-copper complex has good complexing capability and high enantiomer selectivity to phenylalanine enantiomer, and the separation factor alpha is up to over 5.0.
-
Paragraph 0017; 0018

(2017/01/26)

Model tropic alcohol amino acid anionic chiral ion liquid preparation, immobilized and its split DL-phenylalanie and method for DL-tryptophan
The invention discloses a method for preparing a novel tropenol amino acid anionic chiral ionic liquid, an immobilization method thereof and methods for resolving racemic phenylalanine and tryptophan by using the same. The ionic liquid structure disclosed by the invention is represented by a general formula (I) as shown in the specification and is mainly characterized in that the ionic liquid and an inorganic salt solution are formed into aqueous two phases and enriched in the upper layer. The method for resolving the DL-phenylalanine comprises the steps of adding quantitative copper acetate and DL-phenylalanine to the ionic liquid, then adding the quantitative salt solution to form aqueous two phases, layering by centrifuging, enabling D-type phenylalanine to be enriched in the ionic liquid phase and L-type phenylalanine to be enriched in the solid phase. The formula (II) represents a silica-gel-immobilized ionic liquid structure disclosed by the invention. The method for resolving the DL-tryptophan and phenylalanine comprises the steps of enabling the ionic liquid to adsorb metal Cu2 to be saturated and to be used as filler of a column chromatography and firstly eluting D-configuration amino acids prior to L-configuration amino acids. Compared with the existing research, the novel tropenol amino acid anionic chiral ionic liquid disclosed by the invention is prominently characterized in that the ionic liquid structure having the formula (I) has strong capability in phase forming and can be used for resolution of water-soluble type DL-phenylalanine, an organic solvent is not needed and the effect is better.
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Paragraph 0077-0078

(2017/03/22)

Asymmetric Transamination of α-Keto Acids Catalyzed by Chiral Pyridoxamines
A new type of novel chiral pyridoxamines 3a-g containing a side chain has been developed. The pyridoxamines displayed catalytic activity and promising enantioselectivity in biomimetic asymmetric transamination of α-keto acids, to give various α-amino acids in 47-90% yields with up to 87% ee's under very mild conditions. An interesting effect of the side chain on enantioselectivity was observed in the reaction.
Lan, Xiaoyu,Tao, Chuangan,Liu, Xuliang,Zhang, Aina,Zhao, Baoguo
supporting information
p. 3658 - 3661
(2016/08/16)

Single-Biocatalyst Synthesis of Enantiopure d-Arylalanines Exploiting an Engineered d-Amino Acid Dehydrogenase
A practical and efficient biocatalytic synthesis of aromatic d-amino acids has been developed, based on the reductive amination of the corresponding α-keto acids via a recombinant whole cell system composed of an engineered dehydrogenase and cofactor recycling apparatus. The reaction was shown to give excellent enantioselectivity (≥98%) and good yields at the preparative scale across a broad range of substrates. Additionally, the structure of the variant enzyme was solved to allow rationalisation of the observed reaction rates. The engineered whole cell catalyst was also used to mediate the production of d-phenylalanine derivatives from racemic mixtures and cheaper l-amino acids by combining it with an enantiocomplementary deaminase. (Figure presented.).
Parmeggiani, Fabio,Ahmed, Syed T.,Thompson, Matthew P.,Weise, Nicholas J.,Galman, James L.,Gahloth, Deepankar,Dunstan, Mark S.,Leys, David,Turner, Nicholas J.
p. 3298 - 3306
(2016/10/20)

Influence of the aromatic moiety in α- And β-arylalanines on their biotransformation with phenylalanine 2,3-aminomutase from: Pantoea agglomerans
In this study enantiomer selective isomerization of various racemic α- and β-arylalanines catalysed by phenylalanine 2,3-aminomutase from Pantoea agglomerans (PaPAM) was investigated. Both α- and β-arylalanines were accepted as substrates when the aryl moiety was relatively small, like phenyl, 2-, 3-, 4-fluorophenyl or thiophen-2-yl. While 2-substituted α-phenylalanines bearing bulky electron withdrawing substituents did not react, the corresponding substituted β-aryl analogues were converted rapidly. Conversion of 3- and 4-substituted α-arylalanines happened smoothly, while conversion of the corresponding β-arylalanines was poor or non-existent. In the range of pH 7-9 there was no significant influence on the conversion of racemic α- or β-(thiophen-2-yl)alanines, whereas increasing the concentration of ammonia (ammonium carbonate from 50 to 1000 mM) inhibited the isomerization progressively and decreased the amount of the by-product (i.e. (E)-3-(thiophen-2-yl)acrylic acid was detected). In all cases, the high ee values of the products indicated excellent enantiomer selectivity and stereospecificity of the isomerization except for (S)-2-nitro-α-phenylalanine (ee 92%) from the β-isomer. Substituent effects were rationalized by computational modelling revealing that one of the main factors controlling biocatalytic activity was the energy difference between the covalent regioisomeric enzyme-substrate complexes.
Varga, Andrea,Bánóczi, Gergely,Nagy, Botond,Bencze, László Csaba,To?a, Monica Ioana,Gellért, ákos,Irimie, Florin Dan,Rétey, János,Poppe, László,Paizs, Csaba
p. 56412 - 56420
(2016/07/06)

Novel chiral open-chain pyridoxamine catalyst and synthesis method and application thereof
The invention relates to a novel chiral open-chain pyridoxamine catalyst and a synthesis method and application thereof. The structural general formula of the pyridoxamine catalyst is shown in the specification, wherein R1, R2, R3 and R4 are one of hydrogen, C1-24 alkyl, C1-24 alkyl containing substituent groups, substances shown in the specification and halogen, the substituent groups on C1-24 alkyl are a substance shown in the specification or a substance shown in the specification or a substance shown in the specification or O-Rw or S-Rw' or halogen, and Rx, Rx', Ry, Ry', Ry'', Rz, Rz', Rw and Rw' are one of hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, tertiary butyl, cyclopentyl, cyclohexyl, cycloheptyl, phenyl, benzyl, (1-phenyl)ethyl, 1-naphthyl, 2-naphthyl and halogen. Compared with the prior art, the pyridoxamine catalyst can achieve rapid and efficient synthesis of chiral amino acid, the preparation raw materials are easy to obtain, reaction conditions are mild, cost is low, and when the novel chiral open-chain pyridoxamine catalyst is used for a transamination reaction, the conditions are mild, and the reaction is stable.
-
Paragraph 0175; 0176; 0177; 0178; 0185; 0186; 0187; 0188

(2017/01/19)

A L-phenylalanie asymmetric conversion D-phenylalanie method of preparation
The invention discloses a method for preparing D-phenylalanine through asymmetric transformation of L-phenylalanine, and belongs to the technical field of chirality organic compounds. The method comprises steps: dissolving the L-phenylalanine and aldehyde catalysts in organic acid, adding D-tartaric acid, performing a reaction for 5-10 hours at the temperature of 60-90 DEG C, performing cooling and filtration, and washing a solid with an organic solvent so as to obtain D-tartaric acid .D-phenylalanine salt; and adding the obtained D-tartaric acid .D-phenylalanine salt into alkali liquid in batches, performing dissociation, performing a stirring reaction for 1-2 hours, and performing filtration, washing and drying so as to obtain the D-phenylalanine. The method disclosed by the invention solves the problems of poor stability, low resolution efficiency, poor product quality, high production cost and the like existing in the technology of preparing the D-phenylalanine through the L-phenylalanine. The method disclosed by the invention has the advantages of being high in yield, low in production cost, simple to operate, easy in industrialization and the like.
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Paragraph 0025-0026

(2018/02/04)

2-Pyridinyl-N-(2,4-difluorobenzyl)aminoethyl Group As Thermocontrolled Implement for Protection of Carboxylic Acids
A thermolabile protecting group strategy for carboxylic acids is expanded. Thermosensitive esters are readily prepared using a known procedure, and their stability under neutral condition is investigated. Effective thermolytic deprotection initiated only by temperature for different carboxylic acids is demonstrated, and the compatibility of a thermolytic protecting group with acidic and basic protecting groups in an orthogonal protection strategy is also presented. This study showed interesting correlations between the pKa of acids and the deprotection rate of their well-protected moieties.
Brzezinska, Jolanta,Witkowska, Agnieszka,Balbańska, Sandra,Chmielewski, Marcin K.
p. 3230 - 3233
(2016/07/14)

A new type of chiral-pyridoxamines for catalytic asymmetric transamination of α-keto acids
A new type of chiral pyridoxamines bearing an adjacent chiral stereocenter has been developed via multi-step synthesis. The pyridoxamines displayed catalytic activity in asymmetric transamination of α-keto acids to give a variety of optically active amino acids in 27–78% yields with 34–62% ee's under very mild conditions. This work provides a synthetic strategy to construct new chiral pyridoxamines using bromopyridine 7 as a key synthon and also represents an early example of the applications of chiral pyridoxamines in asymmetric catalysis.
Chen, Jianfeng,Zhao, Junyu,Gong, Xing,Xu, Dongfang,Zhao, Baoguo
supporting information
p. 4612 - 4615
(2016/09/23)

Enantioselective ester hydrolysis by an achiral catalyst co-embedded with chiral amphiphiles into a vesicle membrane
Co-embedding of an amphiphilic non-chiral hydrolysis catalyst with amphiphilic chiral additives into the membrane of a phospholipid vesicle induces different rates of ester hydrolysis for enantiomeric amino acid esters.
Poznik,K?nig
p. 44456 - 44458
(2016/06/09)

An easy 'Filter-and-Separate' method for enantioselective separation and chiral sensing of substrates using a biomimetic homochiral polymer
We present a polyfluorene appended with protected l-glutamic acid that exhibited a reversible α-helix/β-sheet-like conformation and helical porous fibrous morphology mimicking the super-structure of proteins. The new homochiral polymer probe enabled efficient heterogeneous enantioselective separation and chiral sensing of a wide variety of substrates from their aqueous racemic mixture using an easy 'Filter-and-Separate' method.
Senthilkumar,Asha
supporting information
p. 8931 - 8934
(2015/05/27)

Fabrication of mesoporous carbon tube and foam: Application as supports in enantio-selective separation of optically pure amino acid from racemates
The mesoporous monolithic carbon (MMC) foams and carbon tubes were newly fabricated in cmscale using the mixture of triblock copolymers and phenol/HCHO resin precursors. The regular mesoporosity were formed in the body of MMC foam and carbon fibers. In this work, the organic phases containing chiral ARCA adsorbent and a phase transfer catalyst were coated on the surfaces of mesoporous carbon support, and this ARCA/carbon mixture was adopted for the enantioselective separation of amino acid in the circulation system. (S)-ARCA coated MMC support showed high selcetivity up to 90% for the separation of D-type phenylalanine, serine and tryptophan from racemic mixtures.
Jeon, Hoon-Gi,Lee, Ju-Hyun,Kim, Gye-Ryung,Park, Da-Min,Kim, Geon-Joong
p. 334 - 338
(2015/03/18)

ｔ-BUTYLKETONE BINAPHTHOL DERIVATIVES AND PREPARING METHOD THEREOF
The present disclosure relates to a t-butylketone binaphthol derivative and a method of preparing the same, the t-butylketone binaphthol derivative being a high-efficiency chiral extracting agent which has a very high chiral selectivity enabling to extract an amino acid from an aqueous solution phase to an organic layer and to facilitate its hydrolysis, and enabling a continuous reuse of the organic layer.
-
Paragraph 0097

(2017/01/17)

AXIAL-ASYMMETRIC N-(2-ACYLARYL)-2-[5, 7-DIHYDRO-6H-DIBENZO [C, E] AZEPINE-6-YL] ACETAMIDE COMPOUND AND CHIRALITY CONVERSION METHOD FOR A-AMINO ACID USING SAME
An object of the present invention is to provide a method for producing an optically active amino acid in high yield and in a highly enantioselective manner, which method has fewer restrictions on the material that can be used as the substrate, and to provide, among others, a compound useful as a chiral auxiliary for the method. The present invention provides an N-(2-acylaryl)-2-[5,7-dihydro-6H-dibenzo[c,e]azepin-6-yl]ac etamide compound represented by Formula (1): or a salt thereof, or a metal complex represented by Formula (3) :
-
Paragraph 0146; 0147; 0148

(2015/11/27)

Ulleungamides A and B, Modified α,β-Dehydropipecolic Acid Containing Cyclic Depsipeptides from Streptomyces sp. KCB13F003
Two novel cyclic depsipeptides, ulleungamides A (1) and B (2), were isolated from cultures of terrestrial Streptomyces sp. Their structures were determined by analyses of spectroscopic data and various chemical transformations, including modified Mosher's method, advanced Marfey's method, PGME, GITC derivatizations, and Snatzke's method. Ulleungamides were determined to be a new class of peptides bearing unprecedented units, such as 5-hydroxy-6-methyl-2,3-dehydropipecolic acid, 4,5-dihydroxy-6-methyl-2,3-dehydropipecolic acid, and amino-linked 2-isopropylsuccinic acid. Ulleungamide A displayed growth inhibitory activity against Staphylococcus aureus and Salmonella typhimurium without cytotoxicity.
Son, Sangkeun,Ko, Sung-Kyun,Jang, Mina,Lee, Jae Kyoung,Ryoo, In-Ja,Lee, Jung-Sook,Lee, Kyung Ho,Soung, Nak-Kyun,Oh, Hyuncheol,Hong, Young-Soo,Kim, Bo Yeon,Jang, Jae-Hyuk,Ahn, Jong Seog
supporting information
p. 4046 - 4049
(2015/09/01)

Efficient synthesis of chiral binaphthol aldehyde with phenyl ether linkage for enantioselective extraction of amino acids
A binaphthol aldehyde with phenyl ether linkage, compound 2, has been synthesized starting from binaphthol-3-carboxylic acid. The axially chiral binaphthol ring was racemized during the synthesis due to high temperatures required in O-phenylation reaction. The enantiomerically pure form of 2 was obtained from the resolution of the diastereomeric imine of 2. Optically pure compound (S)-2 was applied to the enantioselective liquid-liquid extraction of amino acid between CH2Cl2 and aqueous layers.The stereoselectivities, that is, D/L ratio of the amino acid extracted, ranged from 3.57 to 11.1. One carbon was absent in compound (S)-2 compared to the compound (S)-1 with benzyl ether linkage, which differentiated the conformations of their imines formed with amino acids.
Choi, Misun,Jun, Moo-Jin,Kim, Kwan Mook
p. 1834 - 1837
(2015/07/15)

Enantiomeric separation of underivatized amino acids: Predictability of chiral recognition on ristocetin a chiral stationary phase
The present work aimed to investigate the predictability of the chromatographic behavior for the separation of underivatized amino acids on ristocetin A, known as Chirobiotic R, using a DryLab high-performance liquid chromatography (HPLC) method development software, which is typically used to predict the effect of changing various chromatographic parameters on resolution in the reversed phase mode. After implementing the basic runs, and judging the predictability via the computed resolution map, it can be deduced that the chiral recognition mechanisms tend towards a hydrophilic interaction chromatography rather than the reversed phase mode, which limits the ability of DryLab software to predict separations on Chirobiotic R.
Wagdy, Hebatallah A.,Hanafi, Rasha S.,El-Nashar, Rasha M.,Aboul-Enein, Hassan Y.
p. 132 - 135
(2014/03/21)

Coordination properties of 3-functionalised β-cyclodextrins: Thermodynamic stereoselectivity of copper(II) complexes of the 3-histamine derivative and its exploitation in ligand-exchange capillary electrophoresis
A histamine derivative of β-cyclodextrin functionalised at the secondary rim was synthesised and characterised by optical and NMR spectroscopy. Its binary systems both with proton and copper(II) were thermodynamically characterised through pH-metric potentiometry. In addition, the ternary systems with the enantiomers of tryptophan, phenylalanine and alanine were investigated. Thermodynamic stereoselectivity was observed for both the tryptophan and phenylalanine enantiomers. The properties of the synthesised cyclodextrin derivative as a chiral selector were verified in chiral ligand-exchange capillary electrophoresis (CLECE) towards the enantiomeric pairs of some amino acids. A β-cyclodextrin histamine-functionalised at the secondary rim was synthesised and characterised as a chiral selector of aromatic amino acids.
Giuffrida, Alessandro,Cucinotta, Vincenzo,MacCarrone, Giuseppe,Messina, Marianna,Rizzarelli, Enrico,Vecchio, Graziella
p. 377 - 383
(2014/01/23)