- Preparation of a novel bridged bis(β-cyclodextrin) chiral stationary phase by thiol-ene click chemistry for enhanced enantioseparation in HPLC
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A bridged bis(β-cyclodextrin) ligand was firstly synthesized via a thiol-ene click chemistry reaction between allyl-ureido-β-cyclodextrin and 4-4′-thiobisthiophenol, which was then bonded onto a 5 μm spherical silica gel to obtain a novel bridged bis(β-cyclodextrin) chiral stationary phase (HTCDP). The structures of HTCDP and the bridged bis(β-cyclodextrin) ligand were characterized by the 1H nuclear magnetic resonance (1H NMR), solid state 13C nuclear magnetic resonance (13C NMR) spectra spectrum, scanning electron microscope, elemental analysis, mass spectrometry, infrared spectrometry and thermogravimetric analysis. The performance of HTCDP in enantioseparation was systematically examined by separating 21 chiral compounds, including 8 flavanones, 8 triazole pesticides and 5 other common chiral drugs (benzoin, praziquantel, 1-1′-bi-2-naphthol, Tr?ger's base and bicalutamide) in the reversed-phase chromatographic mode. By optimizing the chromatographic conditions such as formic acid content, mobile phase composition, pH values and column temperature, 19 analytes were completely separated with high resolution (1.50-4.48), in which the enantiomeric resolution of silymarin, 4-hydroxyflavanone, 2-hydroxyflavanone and flavanone were up to 4.34, 4.48, 3.89 and 3.06 within 35 min, respectively. Compared to the native β-CD chiral stationary phase (CDCSP), HTCDP had superior enantiomer separation and chiral recognition abilities. For example, HTCDP completely separated 5 other common chiral drugs, 2 flavanones and 3 triazole pesticides that CDCSP failed to separate. Unlike CDCSP, which has a small cavity (0.65 nm), the two cavities in HTCDP joined by the aryl connector could synergistically accommodate relatively bulky chiral analytes. Thus, HTCDP may have a broader prospect in enantiomeric separation, analysis and detection. This journal is
- Gong, Bolin,Guo, Siyu,Zhang, Ning
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p. 35754 - 35764
(2021/12/02)
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- C3 The symmetry contains a chiral ligand H3L of an amide bond. Preparation method and application
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The invention discloses C. 3 Chiral ligand H with symmetric amide bond3 L Relates to the technical field of material chemistry and chiral chemistry. The invention further provides the chiral ligand H. 3 L Preparation method and application thereof. The present invention has the advantage that the chiral ligand H of the present invention is a chiral ligand. 3 The L has a higher C. 3 The symmetric and flexible amide group enables coordination of the lanthanide metal ions with high coordination number and high oxygen affinity to be assembled into a novel structure-structure lanthanide metal chiral porous coordination cage. Moreover, the abundant chiral amide groups and amino acid residues on the ligand framework can be directly introduced into the synthesized lanthanide metal chiral porous coordination cage, thereby being beneficial to generating multiple chiral recognition sites and unique chiral microenvironments which mimic the biological enzyme binding pocket and further realize the purpose of high enantioselectivity separation of a series of chiral small molecule compounds.
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Paragraph 0092-0100
(2021/09/08)
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- Microbial synthesis of (S)- And (R)-benzoin in enantioselective desymmetrization and deracemization catalyzed by aureobasidium pullulans included in the blossom protect agent
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In this study, we examined the Aureobasidium pullulans strains DSM 14940 and DSM 14941 included in the Blossom Protect agent to be used in the bioreduction reaction of a symmetrical dicarbonyl compound. Both chiral 2-hydroxy-1,2-diphenylethanone antipodes were obtained with a high enantiomeric purity. Mild conditions (phosphate buffer [pH 7.0, 7.2], 30 ?C) were successfully employed in the synthesis of (S)-benzoin using two different methodologies: benzyl desymmetrization and rac-benzoin deracemization. Bioreduction carried out with higher reagent concentrations, lower pH values and prolonged reaction time, and in the presence of additives, enabled enrichment of the reaction mixture with (R)-benzoin. The described procedure is a potentially useful tool in the synthesis of chiral building blocks with a defined configuration in a simple and economical process with a lower environmental impact, enabling one-pot biotransformation.
- Ko?odziejska, Renata,Studzinska, Renata,Tafelska-Kaczmarek, Agnieszka,Pawluk, Hanna,Mlicka, Dominika,Wozniak, Alina
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- Homochiral Dodecanuclear Lanthanide "cage in Cage" for Enantioselective Separation
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It is extremely difficult to anticipate the structure and the stereochemistry of a complex, particularly when the ligand is flexible and the metal node adopts diverse coordination numbers. When trivalent lanthanides (LnIII) and enantiopure amino acid ligands are utilized as building blocks, self-assembly sometimes yields rare chiral polynuclear structures. In this study, an enantiopure carboxyl-functionalized amino acid-based ligand with C3 symmetry reacts with lanthanum cations to give a homochiral porous coordination cage, (Δ/λ)12-PCC-57. The dodecanuclear lanthanide cage has an unprecedented octahedral "cage-in-cage"framework. During the self-assembly, the chirality is transferred from the enantiopure ligand and fixed by the binuclear lanthanide cluster to give 12 metal centers that have either Δor λ homochiral stereochemistry. The cage exhibits excellent enantioselective separation of racemic alcohols, 2,3-dihydroquinazolinones, and multiple commercially available drugs. This finding exhibits a rare example of a multinuclear lanthanide complex with a dual-walled topology and homochirality. The highly ordered self-assembly and self-sorting of flexible amino acids and lanthanides shed light on the chiral transformation between different complicated artificial systems that mimic natural enzymes.
- Zhu, Chengfeng,Tang, Haitong,Yang, Keke,Fang, Yu,Wang, Kun-Yu,Xiao, Zhifeng,Wu, Xiang,Li, Yougui,Powell, Joshua A.,Zhou, Hong-Cai
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supporting information
p. 12560 - 12566
(2021/08/23)
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- Structural insights into the desymmetrization of bulky 1,2-dicarbonyls through enzymatic monoreduction
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Benzil reductases are dehydrogenases preferentially active on aromatic 1,2-diketones, but the reasons for this peculiar substrate recognition have not yet been clarified. The benzil reductase (KRED1-Pglu) from the non-conventional yeast Pichia glucozyma showed excellent activity and stereoselectivity in the monoreduction of space-demanding aromatic 1,2-dicarbonyls, making this enzyme attractive as biocatalyst in organic chemistry. Structural insights into the stereoselective monoreduction of 1,2-diketones catalyzed by KRED1-Pglu were investigated starting from its 1.77 ? resolution crystal structure, followed by QM and classical calculations; this study allowed for the identification and characterization of the KRED1-Pglu reactive site. Once identified the recognition elements involved in the stereoselective desymmetrization of bulky 1,2-dicarbonyls mediated by KRED1-Pglu, a mechanism was proposed together with an in silico prediction of substrates reactivity.
- Rabuffetti, Marco,Cannazza, Pietro,Contente, Martina Letizia,Pinto, Andrea,Romano, Diego,Hoyos, Pilar,Alcantara, Andres R.,Eberini, Ivano,Laurenzi, Tommaso,Gourlay, Louise,Di Pisa, Flavio,Molinari, Francesco
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supporting information
(2021/01/25)
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- Enantioselective Acyloin Rearrangement of Acyclic Aldehydes Catalyzed by Chiral Oxazaborolidinium Ion
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A catalytic enantioselective acyloin rearrangement of acyclic aldehydes to synthesize highly optically active acyloin derivatives is described. In the presence of a chiral oxazaborolidinium ion catalyst, the reaction provided chiral α-hydroxy aryl ketones in high yield (up to 95%) and enantioselectivity (up to 98% ee). In addition, the enantioselective acyloin rearrangement of α,α-dialkyl-α-siloxy aldehydes produced chiral α-siloxy alkyl ketones in high yield (up to 92%) with good enantioselectivity (up to 89% ee).
- Cho, Soo Min,Lee, Si Yeon,Ryu, Do Hyun
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supporting information
p. 1516 - 1520
(2021/03/03)
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- Enantioselective N-heterocyclic carbene-catalysed intermolecular crossed benzoin condensations: Improved catalyst design and the role of in situ racemisation
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The enantioselective intermolecular crossed-benzoin condensation mediated by novel chiral N-heterocyclic carbenes derived from pyroglutamic acid has been investigated. A small library of chiral triazolium ions were synthesised. Each possessed a tertiary alcohol H-bond donor and a variable N-aryl substituent. It was found that increasing both the steric requirement and the electron-withdrawing characteristics of the N-aryl ring led to more chemoselective, efficient and enantioselective chemistry, however both quenching the reaction at different times and deuterium incorporation experiments involving the product revealed that this is complicated by product racemisation in situ (except in the case of benzoin itself), which explains the dependence of enantioselectivity on the electrophilicity of the reacting aldehydes common in the literature. Subsequent protocol optimisation, where one reacting partner was an o-substituted benzaldehyde, allowed a range of crossed-benzoins to be synthesised in moderate-good yields with moderate to excellent enantioselectivity.
- Delany, Eoghan G.,Connon, Stephen J.
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supporting information
p. 248 - 258
(2021/01/14)
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- Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
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Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
- Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
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p. 1080 - 1090
(2020/05/25)
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- Catalytic Asymmetric Acyloin Rearrangements of α-Ketols, α-Hydroxy Aldehydes, and α-Iminols by N, N′-Dioxide-Metal Complexes
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A highly enantioselective acyloin rearrangement of cyclic α-ketols has been developed with a chiral Al(III)-N,N′-dioxide complex as catalyst. This strategy provided an array of optically active 2-acyl-2-hydroxy cyclohexanones in moderate to good yields with high enantioselectivities. The asymmetric isomerizations of acyclic α-hydroxy aldehydes and α-iminols were achieved as well under modified conditions, affording the corresponding chiral α-hydroxy ketones and α-amino ketones in moderate results. Moreover, further transformations of product to enantioenriched diols were carried out.
- Dai, Li,Li, Xiangqiang,Zeng, Zi,Dong, Shunxi,Zhou, Yuqiao,Liu, Xiaohua,Feng, Xiaoming
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supporting information
p. 5041 - 5045
(2020/07/03)
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- Asymmetric aerobic oxidation of secondary alcohols catalyzed by poly(: N-vinyl-2-pyrrolidone)-stabilized gold clusters modified with cyclodextrin derivatives
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Surface modification of poly(N-vinyl-2-pyrrolidone)-stabilized gold clusters (1.8 ± 0.6 nm) with aminated cyclodextrins induced aerobic oxidative kinetic resolution of racemic secondary alcohols (krel = 1.2).
- Hirano, Koto,Takano, Shinjiro,Tsukuda, Tatsuya
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supporting information
p. 15033 - 15036
(2020/01/03)
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- HPLC with cellulose Tris (3,5-DimethylPhenylcarbamate) chiral stationary phase: Influence of coating times and coating amount on chiral discrimination
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Coating cellulose tris (3,5-dimethylphenylcarbamate) (CDMPC) on silica gels with large pores have been demonstrated as an efficient way for the preparation of chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC). During the process, a number of parameters, including the type of coating solvent, amount of coating, and the method for subsequent solvent removing, have been proved to affect the performance of the resultant CSPs. Coating times and the concentration of coating solution, however, also makes a difference to CSPs' performance by changing the arrangement of cellulose derivatives while remaining the coating amount constant, have much less been studied before, and thereby, were systematically investigated in this work. Results showed that CSPs with more coating times exhibited higher chiral recognition and column efficiency, suggesting that resolution was determined by column efficiency herein. Afterwards, we also investigated the effect of coating amount on the performance of CSPs, and it was shown that the ability of enantio-recognition did not increase all the time as the coating amount; and four of seven racemates achieved best resolution when the coating amount reached to 18.37%. At the end, the reproducibility of CDMPC-coated CSPs were further confirmed by two methods, ie, reprepared the CSP-0.15-3 and reevaluated the effect of coating times.
- Wei, Qiuhong,Su, Hongjiu,Gao, Diannan,Wang, Shudong
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p. 164 - 173
(2019/01/18)
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- Three-State Switchable Chiral Stationary Phase Based on Helicity Control of an Optically Active Poly(phenylacetylene) Derivative by Using Metal Cations in the Solid State
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An unprecedented three-state switchable chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) was developed using a helical poly(phenylacetylene) bearing a chiral (R)-α-methoxyphenylacetic acid residue as the pendant (poly-1). The left- and right-handed helical conformations were induced in poly-1-based CSP upon coordination with a catalytic amount of soluble sodium and cesium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate salts (MBArF), respectively, which are soluble in the HPLC conditions [hexane-2-propanol (95:5, v/v)]. The switch between the two different helical states of poly-1 can be easily achieved by rinsing the poly-1-based CSP with MeOH and the subsequent addition of the proper MBArF salt. Using this dynamic helical CSP, we demonstrate how changes on the orientation of the secondary structure of a chiral polymer (right-handed, left-handed, and racemic helices) can alter and even invert the elution order of the enantiomers. This study was done without adding chiral additives or changing the mobile phase, which could produce changes on the retention times and make it more difficult to determine the role of the secondary structure during the chiral recognition process.
- Hirose, Daisuke,Isobe, Asahi,Qui?oá, Emilio,Freire, Félix,Maeda, Katsuhiro
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supporting information
(2019/06/10)
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- Three-State Switchable Chiral Stationary Phase Based on Helicity Control of an Optically Active Poly(phenylacetylene) Derivative by Using Metal Cations in the Solid State
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An unprecedented three-state switchable chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) was developed using a helical poly(phenylacetylene) bearing a chiral (R)-α-methoxyphenylacetic acid residue as the pendant (poly-1). The left- and right-handed helical conformations were induced in poly-1-based CSP upon coordination with a catalytic amount of soluble sodium and cesium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate salts (MBArF), respectively, which are soluble in the HPLC conditions [hexane-2-propanol (95:5, v/v)]. The switch between the two different helical states of poly-1 can be easily achieved by rinsing the poly-1-based CSP with MeOH and the subsequent addition of the proper MBArF salt. Using this dynamic helical CSP, we demonstrate how changes on the orientation of the secondary structure of a chiral polymer (right-handed, left-handed, and racemic helices) can alter and even invert the elution order of the enantiomers. This study was done without adding chiral additives or changing the mobile phase, which could produce changes on the retention times and make it more difficult to determine the role of the secondary structure during the chiral recognition process.
- Hirose, Daisuke,Isobe, Asahi,Qui?oá, Emilio,Freire, Félix,Maeda, Katsuhiro
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supporting information
p. 8592 - 8598
(2019/06/13)
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- Homochiral Metal-Organic Frameworks for Enantioselective Separations in Liquid Chromatography
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Selective separation of enantiomers is a substantial challenge for the pharmaceutical industry. Chromatography on chiral stationary phases is the standard method, but at a very high cost for industrial-scale purification due to the high cost of the chiral stationary phases. Typically, these materials are poorly robust, expensive to manufacture, and often too specific for a single desired substrate, lacking desirable versatility across different chiral analytes. Here, we disclose a porous, robust homochiral metal-organic framework (MOF), TAMOF-1, built from copper(II) and an affordable linker prepared from natural l-histidine. TAMOF-1 has shown to be able to separate a variety of model racemic mixtures, including drugs, in a wide range of solvents of different polarity, outperforming several commercial chiral columns for HPLC separations. Although not exploited in the present article, it is worthy to mention that the preparation of this new material is scalable to the multikilogram scale, opening unprecedented possibilities for low-energy chiral separation at the industrial scale.
- Corella-Ochoa, M. Nieves,Tapia, Jesús B.,Rubin, Heather N.,Lillo, Vanesa,González-Cobos, Jesús,Nú?ez-Rico, José Luis,Balestra, Salvador R.G.,Almora-Barrios, Neyvis,Lledós, Marina,Gu?ll-Bara, Arnau,Cabezas-Giménez, Juanjo,Escudero-Adán, Eduardo C.,Vidal-Ferran, Anton,Calero, Sofiá,Reynolds, Melissa,Martí-Gastaldo, Carlos,Galán-Mascarós, José Ramón
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p. 14306 - 14316
(2019/10/11)
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- Two enantiocomplementary ephedrine dehydrogenases from arthrobacter sp. TS-15 with broad substrate specificity
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The recently identified pseudoephedrine and ephedrine dehydrogenases (PseDH and EDH, respectively) from Arthrobacter sp. TS-15 are NADH-dependent members of the oxidoreductase superfamily of short-chain dehydrogenases/reductases (SDRs). They are specific for the enantioselective oxidation of (+)-(S) N-(pseudo)ephedrine and (-)-(R) N-(pseudo)ephedrine, respectively. Anti-Prelog stereospecific PseDH and Prelog-specific EDH catalyze the regio- A nd enantiospecific reduction of 1-phenyl-1,2-propanedione to (S)-phenylacetylcarbinol and (R)-phenylacetylcarbinol with full conversion and enantiomeric excess of >99%. Moreover, they perform the reduction of a wide range of aryl-aliphatic carbonyl compounds, including ketoamines, ketoesters, and haloketones, to the corresponding enantiopure alcohols. The highest stability of PseDH and EDH was determined to be at a pH range of 6.0-8.0 and 7.5-8.5, respectively. PseDH was more stable than EDH at 25 °C with half-lives of 279 and 38 h, respectively. However, EDH is more stable at 40 °C with a 2-fold greater half-life than at 25 °C. The crystal structure of the PseDH-NAD+ complex, refined to a resolution of 1.83 ?, revealed a tetrameric structure, which was confirmed by solution studies. A model of the active site in complex with NAD+ and 1-phenyl-1,2-propanedione suggested key roles for S143 and W152 in recognition of the substrate and positioning for the reduction reaction. The wide substrate spectrum of these dehydrogenases, combined with their regio- A nd enantioselectivity, suggests a high potential for the industrial production of valuable chiral compounds.
- Shanati, Tarek,Lockie, Cameron,Beloti, Lilian,Grogan, Gideon,Ansorge-Schumacher, Marion B.
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p. 6202 - 6211
(2019/08/15)
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- Rearrangement of N- tert-Butanesulfinyl Enamines for Synthesis of Enantioenriched α-Hydroxy Ketone Derivatives
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Treating chiral N-tert-butanesulfinyl ketimines with potassium hexamethyldisilazide (or potassium tert-butoxide) and methyl triflate gives N-methylated N-tert-butanesulfinyl enamine intermediates that undergo stereoselective [2,3]-rearrangement to afford α-sulfenyloxy ketones with excellent enantiopurities. This cascade of enamination-N-methylation-rearrangement was even used to generate acyclic tertiary α-hydroxy ketones bearing two α-substituents showing negligible differences in bulkiness, such as methyl and ethyl groups.
- Li, Chun-Tian,Liu, Hui,Yao, Yun,Lu, Chong-Dao
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p. 8383 - 8388
(2019/10/14)
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- Synthesis of Tridentate Chiral Spiro Aminophosphine?Oxazoline Ligands and Application to Asymmetric Hydrogenation of α-Keto Amides
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A new type of tridentate chiral spiro aminophosphine?oxazoline ligands (SpiroOAP) have been synthesized through four steps. The SpiroOAP ligands are highly efficient for the asymmetric hydrogenation of α-keto amides, providing a variety of synthetically useful α-hydroxy amides with excellent enantioselectivity (up to 98% ee) and turnover numbers (up to 10,000). (Figure presented.).
- Zhang, Feng-Hua,Wang, Chen,Xie, Jian-Hua,Zhou, Qi-Lin
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supporting information
p. 2832 - 2835
(2019/04/13)
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- Light-assisted preparation of a cyclodextrin-based chiral stationary phase and its separation performance in liquid chromatography
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A cyclodextrin-based chiral stationary phase (CD-CSP) is one of the most widely applied CSPs due to its powerful enantioseparation ability. In this study, a facile method was developed to prepare a CD-CSP via carboxyl methyl β-cyclodextrin (CD-COOH) and diazo-resin (DR). Monodisperse silica particles were synthesized using a modified St?ber method. Then DR and CD-COOH were coated on the silica particles via ionic bonding successively and UV light was finally used to couple silica, DR and CD-COOH and the ionic bonds turned into covalent bonds. The resultant CD-DR silica particles were characterized using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA) and scanning electron microscopy (SEM). The enantioselectivity of the CD@SiO2 particles was explored in reversed phase high-performance liquid chromatography (RP-HPLC). Baseline separation of chiral drugs was achieved and the effects of separation parameters (elution mode, buffer and analyte mass) were investigated in detail. By using water soluble non-toxic DR to replace a highly toxic and moisture sensitive silane agent to modify silica microspheres, this light-assisted strategy can provide a green and effective technique to manufacture packing materials for enantioseparation applications.
- Tang, Qi,Yu, Bing,Gao, Lilong,Cong, Hailin,Zhang, Shuai
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p. 1115 - 1120
(2018/02/06)
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- Cellulose type chiral stationary phase based on reduced graphene oxide@silica gel for the enantiomer separation of chiral compounds
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The graphene oxide (GO) was covalently coupled to the surfaces of silica gel (SiO2) microspheres by amide bond to get the graphene oxide@silica gel (GO@SiO2). Then, the GO@SiO2 was reduced with hydrazine to the reduced graphene oxide@silica gel (rGO@SiO2), and the cellulose derivatives were physically coated on the surfaces of rGO@SiO2 to prepare a chiral stationary phase (CSP) for high performance liquid chromatography. Under the optimum experimental conditions, eight benzene-enriched enantiomers were separated completely, and the resolution of trans-stilbene oxide perfectly reached 4.83. Compared with the blank column of non-bonded rGO, the separation performance is better on the new CSP, which is due to the existence of rGO to produce special retention interaction with analytes, such as π-π stacking, hydrophobic effect, π-π electron-donor–acceptor interaction, and hydrogen bonding. Therefore, the obtained CSP shows special selectivity for benzene-enriched enantiomers, improves separation selectivity and efficiency, and rGO plays a synergistic effect with cellulose derivatives on enantioseparation.
- Li, Yuanyuan,Li, Qiang,Zhu, Nan,Gao, Zhuxian,Ma, Yulong
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p. 996 - 1004
(2018/07/29)
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- N-Heterocyclic Carbene-Catalyzed Asymmetric Benzoin Reaction in Water
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A chiral N-heterocyclic carbene-catalyzed benzoin condensation reaction in water has been developed, affording α-hydroxy ketones in good to high yields and high enantioselectivities. Water was proposed as a proton shuttle in the aqueous asymmetric condens
- Yan, Jun,Sun, Rong,Shi, Kuangxi,Li, Kai,Yang, Limin,Zhong, Guofu
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p. 7547 - 7552
(2018/06/22)
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- Ultrafast chiral separations for high throughput enantiopurity analysis
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Recent developments in fast chromatographic enantioseparations now make high throughput analysis of enantiopurity on the order of a few seconds achievable. Nevertheless, routine chromatographic determinations of enantiopurity to support stereochemical investigations in pharmaceutical research and development, synthetic chemistry and bioanalysis are still typically performed on the 5-20 min timescale, with many practitioners believing that sub-minute enantioseparations are not representative of the molecules encountered in day to day research. In this study we develop ultrafast chromatographic enantioseparations for a variety of pharmaceutically-related drugs and intermediates, showing that sub-minute resolutions are now possible in the vast majority of cases by both supercritical fluid chromatography (SFC) and reversed phase liquid chromatography (RP-LC). Examples are provided illustrating how such methods can be routinely developed and used for ultrafast high throughput analysis to support enantioselective synthesis investigations.
- Barhate, Chandan L.,Joyce, Leo A.,Makarov, Alexey A.,Zawatzky, Kerstin,Bernardoni, Frank,Schafer, Wes A.,Armstrong, Daniel W.,Welch, Christopher J.,Regalado, Erik L.
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supporting information
p. 509 - 512
(2017/01/13)
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- Chromatographic enantioseparation by poly(biphenylylacetylene) derivatives with memory of both axial chirality and macromolecular helicity
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Novel poly(biphenylylacetylene) derivatives bearing two acetyloxy groups at the 2- and 2′-positions and an alkoxycarbonyl group at the 4′-position of the biphenyl pendants (poly-Ac's) were synthesized by the polymerization of the corresponding biphenylylacetylenes using a rhodium catalyst. The obtained stereoregular (cis-transoidal) poly-Ac's folded into a predominantly one-handed helical conformation accompanied by a preferred-handed axially twisted conformation of the biphenyl pendants through noncovalent interactions with a chiral alcohol and both the induced main-chain helicity and the pendant axial chirality were maintained, that is, memorized, after complete removal of the chiral alcohol. The stability of the helicity memory of the poly-Ac's in a solution was lower than that of the analogous poly(biphenylylacetylene)s bearing two methoxymethoxy groups at the 2- and 2′-positions of the biphenyl pendants (poly-MOM's). In the solid state, however, the helicity memory of the poly-Ac's was much more stable and showed a better chiral recognition ability toward several racemates than that of the previously reported poly-MOM when used as a chiral stationary phase for high-performance liquid chromatography. In particular, the poly-Ac-based CSP with a helicity memory efficiently separated racemic benzoin derivatives into enantiomers.
- Ishidate, Ryoma,Ikai, Tomoyuki,Kanoh, Shigeyoshi,Yashima, Eiji,Maeda, Katsuhiro
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p. 120 - 129
(2017/04/24)
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- Preparation and evaluation of regioselectively substituted amylose derivatives for chiral separations
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Six novel regioselectively substituted amylose derivatives with a benzoate at 2-position and two different phenylcarbamates at 3- and 6-positions were synthesized and their structures were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. Their enantioseparation abilities were then examined as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) after they were coated on 3-aminopropyl silica gels. Investigations indicated that the substituents at the 3- and 6-positions played an important role in chiral recognition of these amylose 2-benzoate serial derivatives. The derivatives demonstrated characteristic enantioseparation and some racemates were better resolved on these derivatives than on Chiralpak AD, which is one of the most efficient CSPs, utilizing coated amylose tris(3,5-dimethylphenylcarbamate) as the chiral selector. Among the derivatives prepared, amylose 2-benzoate-3-(phenylcarbamate/4-methylphenylcarbamate)-6-(3,5-dimethylphenylcarbamate) exhibited chiral recognition abilities comparable to that of Chiralpak AD and may be useful CSPs in the future. The effect of mobile phase on chiral recognition was also studied. In general, with the decreased concentration of 2-propanol, better resolutions were obtained with longer retention times. Moreover, when ethanol was used instead of 2-propanol, poorer resolutions were often achieved. However, in some cases, improved enantioselectivity was achieved with ethanol rather than 2-propanol as the mobile phase modifier.
- Tang, Shouwan,Jin, Zhaolei,Sun, Baishen,Wang, Fang,Tang, Wenyuan
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p. 512 - 521
(2017/08/26)
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- Organocatalytic Enantioselective Protonation for Photoreduction of Activated Ketones and Ketimines Induced by Visible Light
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The first catalytic asymmetric photoreduction of 1,2-diketones and α-keto ketimines under visible light irradiation is reported. A transition-metal-free synergistic catalysis platform harnessing dicyanopyrazine-derived chromophore (DPZ) as the photoredox catalyst and a non-covalent chiral organocatalyst is effective for these transformations. With the flexible use of a chiral Br?nsted acid or base in H+ transfer interchange to control the elusive enantioselective protonation, a variety of chiral α-hydroxy ketones and α-amino ketones were obtained with high yields and enantioselectivities.
- Lin, Lu,Bai, Xiangbin,Ye, Xinyi,Zhao, Xiaowei,Tan, Choon-Hong,Jiang, Zhiyong
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supporting information
p. 13842 - 13846
(2017/10/24)
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- Hydrogen Bonding-Assisted Enhancement of the Reaction Rate and Selectivity in the Kinetic Resolution of d,l-1,2-Diols with Chiral Nucleophilic Catalysts
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An extremely efficient acylative kinetic resolution of d,l-1,2-diols in the presence of only 0.5 mol% of binaphthyl-based chiral N,N-4-dimethylaminopyridine was developed (selectivity factor of up to 180). Several key experiments revealed that hydrogen bonding between the tert-alcohol unit(s) of the catalyst and the 1,2-diol unit of the substrate is critical for accelerating the rate of monoacylation and achieving high enantioselectivity. This catalytic system can be applied to a wide range of substrates involving racemic acyclic and cyclic 1,2-diols with high selectivity factors. The kinetic resolution of d,l-hydrobenzoin and trans-1,2-cyclohexanediol on a multigram scale (10 g) also proceeded with high selectivity and under moderate reaction conditions: (i) very low catalyst loading (0.1 mol%); (ii) an easily achievable low reaction temperature (0 °C); (iii) high substrate concentration (1.0 M); and (iv) short reaction time (30 min). (Figure presented.).
- Fujii, Kazuki,Mitsudo, Koichi,Mandai, Hiroki,Suga, Seiji
-
supporting information
p. 2778 - 2788
(2017/08/23)
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- Base-Free Asymmetric Transfer Hydrogenation of 1,2-Di- and Monoketones Catalyzed by a (NH)2P2-Macrocyclic Iron(II) Hydride
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The hydride isonitrile complex [FeH(CNCEt3)(1 a)]BF4 (2) containing a chiral P2(NH)2 macrocycle (1 a), in the presence of 2-propanol as hydrogen donor, catalyzes the base-free asymmetric transfer hydrogenation (ATH) of prostereogenic ketones to alcohols and the hemihydrogenation of benzils to benzoins, which contain a base-labile stereocenter. Benzoins are formed in up to 83 % isolated yield with enantioselectivity reaching 95 % ee. Ketones give the same enantioselectivity observed with the parent catalytic system [Fe(CNCEt3)2(1 a)] (3 a) that operates with added NaOtBu.
- De Luca, Lorena,Mezzetti, Antonio
-
supporting information
p. 11949 - 11953
(2017/09/20)
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- Organocatalytic Enantioselective Acyloin Rearrangement of α-Hydroxy Acetals to α-Alkoxy Ketones
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We report an unprecedented organocatalytic enantioselective acyloin rearrangement of α,α-disubstituted α-hydroxy acetals. In the presence of a catalytic amount of chiral binol-derived N-triflyl phosphoramide, α-hydroxy acetals rearranged to α-alkoxy ketones in good to high yields with high enantioselectivities. Formation of an ion pair between the in situ generated oxocarbenium ion and the chiral phosphoramide anion was proposed to be responsible for the highly efficient transfer of chirality. Conditions for removal of cyclohexyl and cyclopentyl groups from the corresponding α-alkoxy ketones were uncovered underpinning their potential general utility as hydroxy protecting groups. Conversion of the rearranged products to the enantioenriched α-hydroxy ketone, 1,2-diol, β-amino alcohol and 1,4-dioxane was also documented.
- Wu, Hua,Wang, Qian,Zhu, Jieping
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supporting information
p. 5858 - 5861
(2017/05/12)
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- Investigation of a new chiral auxiliary derived chemoenzymatically from toluene: Experimental and computational study
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A tricyclic chiral auxiliary, prepared from the enzymatically derived cis-arene dihydrodiol metabolite of toluene, was investigated as a means of asymmetric induction in several different reactions. The auxiliary was converted to an oxaziridine, and its u
- ?najdr, Ivan,Froese, Jordan,Dudding, Travis,Horáková, Pavlína,Hudlicky, Tomá?
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p. 848 - 856
(2016/10/24)
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- HPLC enantioseparation on a homochiral MOF-silica composite as a novel chiral stationary phase
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The last frontier in the development of chiral stationary phases for chromatographic enantioseparation involves homochiral metal-organic frameworks (MOFs). Using enantiopure (R)-2,2′-dihydroxy-1,1′-binaphthalene-6,6′-dicarboxylic acid as a starting material, we prepared three homochiral MOFs that were further used as chiral stationary phases for high-performance liquid chromatography to separate the enantiomers of various kinds of racemic sulfoxides, sec-alcohols, β-lactams, benzoins, flavanones and epoxides. The experimental results showed excellent performances for enantioseparation, and highlighted that enantioseparation on homochiral MOF columns is practical.
- Tanaka, Koichi,Muraoka, Toshihide,Otubo, Yasuhiro,Takahashi, Hiroki,Ohnishi, Atsushi
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p. 21293 - 21301
(2016/03/08)
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- A 3D Homochiral MOF [Cd2(d-cam)3]?2Hdma?4dma for HPLC Chromatographic Enantioseparation
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Up to now, some chiral metal-organic frameworks (MOFs) have been reported for enantioseparation in liquid chromatography. Here we report a homochiral MOF, [Cd2(d-cam)3]·2Hdma·4dma, used as a new chiral stationary phase for high-performance liquid chromatographic enantioseparation. Nine racemates of alcohol, naphthol, ketone, and base compounds were used as analytes for evaluating the separation properties of the chiral MOF packed column. Moreover, some effects such as mobile phase composition, column temperature, and analytes mass for separations on this chiral column also were investigated. The relative standard deviations for the resolution values of run-to-run and column-to-column were less than 2.1% and 3.2%, respectively. The experimental results indicate that the homochiral MOF offered good recognition ability, which promotes the application of chiral MOFs use as stationary phase for enantioseparation. Chirality 28:340-346, 2016.
- Zhang, Mei,Chen, Xinglian,Zhang, Junhui,Kong, Jiao,Yuan, Liming
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p. 340 - 346
(2016/03/19)
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- Nanocellulose derivative/silica hybrid core-shell chiral stationary phase: Preparation and enantioseparation performance
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Core-shell silica microspheres with a nanocellulose derivative in the hybrid shell were successfully prepared as a chiral stationary phase by a layer-by-layer self-assembly method. The hybrid shell assembled on the silica core was formed using a surfactant as template by the copolymerization reaction of tetraethyl orthosilicate and the nanocellulose derivative bearing triethoxysilyl and 3,5-dimethylphenyl groups. The resulting nanocellulose hybrid core-shell chiral packing materials (CPMs) were characterized and packed into columns, and their enantioseparation performance was evaluated by high performance liquid chromatography. The results showed that CPMs exhibited uniform surface morphology and core-shell structures. Various types of chiral compounds were efficiently separated under normal and reversed phase mode. Moreover, chloroform and tetrahydrofuran as mobile phase additives could obviously improve the resolution during the chiral separation processes. CPMs still have good chiral separation property when eluted with solvent systems with a high content of tetrahydrofuran and chloroform, which proved the high solvent resistance of this new material.
- Zhang, Xiaoli,Wang, Litao,Dong, Shuqing,Zhang, Xia,Wu, Qi,Zhao, Liang,Shi, Yanping
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- Synthesis of optically active poly(diphenylacetylene)s using polymer reactions and an evaluation of their chiral recognition abilities as chiral stationary phases for HPLC
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A series of optically active poly(diphenylacetylene) derivatives bearing a chiral substituent (poly-2S) or chiral and achiral substituents (poly-(2Sx-co-31-x)) on all of their pendant phenyl rings were synthesized by the reaction of poly(bis(4-carboxyphenyl)acetylene) with (S)-1-phenylethylamine ((S)-2) or benzylamine (3) in the presence of a condensing reagent. Their chiroptical properties and chiral recognition abilities as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) were investigated. Poly-2S and poly-(2Sx-co-31-x) (0.06 x-co-31-x)). Furthermore, h-poly-2S and h-poly-(2S0.36-co-30.64) emitted circularly polarized luminescence with opposite signs. h-Poly-2S showed higher chiral recognition abilities toward a larger number of racemates than poly-2S without a preferred-handed helicity and the previously reported preferred-handed poly(diphenylacetylene) derivative bearing the same chiral substituent on half of its pendant phenyl rings. h-Poly-(2S0.36-co-30.64) also exhibited good chiral recognition abilities toward several racemates, though the elution order of some enantiomers was reversed compared with h-poly-2S.
- Maeda, Katsuhiro,Maruta, Miyuki,Sakai, Yuki,Ikai, Tomoyuki,Kanoh, Shigeyoshi
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- Temperature-triggered switchable helix-helix inversion of poly(phenylacetylene) bearing L-valine ethyl ester pendants and its chiral recognition ability
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A phenylacetylene containing the L-valine ethyl ester pendant (PAA-Val) was synthesized and polymerized by an organorhodium catalyst (Rh(nbd)BPh4) to produce the corresponding one-handed helical cis-poly(phenylacetylene) (PPAA-Val). PPAA-Val showed a unique temperature-triggered switchable helix-sense in chloroform, while it was not observed in highly polar solvents, such as N,N′-dimethylformamide (DMF). By heating the solution of PPAA-Val in chloroform, the sign of the CD absorption became reversed, but recovered after cooling the solution to room temperature. Even after six cycles of the heating-cooling treatment, the helix sense of the PPAA-Val's backbone was still switchable without loss of the CD intensity. The PPAA-Val was then coated on silica gel particles to produce novel chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC). These novel PPAA-Val based CSPs showed a high chiral recognition ability for racemic mandelonitrile (α = 2.18) and racemic trans-N,N′-diphenylcyclohexane-1,2-dicarboxamide (α = 2.60). Additionally, the one-handed helical cis-polyene backbone of PPAA-Val was irreversibly destroyed to afford PPAA-Val-H by heating in dimethyl sulfoxide (DMSO) accompanied by the complete disappearance of the Cotton effect. Although PPAA-Val-H had the same L-valine ethyl ester pendants as its cis-isomer PPAA-Val, it showed no chiral recognition. It was concluded that the one-handed helical cis-polyene backbone of PPAA-Val plays an important role in the chiral recognition ability.
- Zhou, Yanli,Zhang, Chunhong,Qiu, Yuan,Liu, Lijia,Yang, Taotao,Dong, Hongxing,Satoh, Toshifumi,Okamoto, Yoshio
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- Solvent-Free Benzoin and Stetter Reactions with a Small Amount of NHC Catalyst in the Liquid or Semisolid State
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The intermolecular or intramolecular asymmetric benzoin reaction was catalyzed by a small amount of N-heterocyclic carbene (NHC) (0.2-1 mol %) under solvent-free conditions. The solvent-free intramolecular asymmetric Stetter reaction also proceeded efficiently with NHC (0.2-1 mol %). In some cases, even solid-to-solid or solid-to-liquid conversions took place with low catalyst loading (0.2-1 mol %).
- Ema, Tadashi,Nanjo, Yoshiko,Shiratori, Sho,Terao, Yuta,Kimura, Ryo
-
supporting information
p. 5764 - 5767
(2016/11/17)
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- Enantioselective benzoin condensation catalyzed by spirocyclic terpene-based N-heterocyclic carbenes
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The synthesis of new chiral spirocyclic triazolium salts, derived from (1S)-fenchone and (1R)-camphorquinone, are described. These salts, which are N-heterocyclic carbene precatalysts, were successfully employed in the catalytic asymmetric benzoin condensation affording acyloins with good yields and moderate enantioselectivities.
- Rafiński, Zbigniew
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p. 1860 - 1867
(2017/03/10)
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- Chiral Frustrated Lewis Pairs Catalyzed Highly Enantioselective Hydrosilylations of 1,2-Dicarbonyl Compounds
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A highly enantioselective hydrosilylation of 1,2-dicarbonyl compounds was successfully realized for the first time utilizing the combination of tricyclohexylphosphine and chiral alkenylborane derived in situ from diyne as a frustrated Lewis pair catalyst. A variety of optically active α-hydroxy ketones and esters were obtained in 52-98% yields with 86-99% ee's.
- Ren, Xiaoyu,Du, Haifeng
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p. 810 - 813
(2016/02/09)
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- Stereoselective reduction of aromatic ketones by a new ketoreductase from Pichia glucozyma
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A new NADPH-dependent benzil reductase (KRED1-Pglu) was identified from the genome of the non-conventional yeast Pichia glucozyma CBS 5766 and overexpressed in E. coli. The new protein was characterised and reaction parameters were optimised for the enantioselective reduction of benzil to (S)-benzoin. A thorough study of the substrate range of KRED1-Pglu was conducted; in contrast to most other known ketoreductases, KRED1-Pglu prefers space-demanding substrates, which are often converted with high stereoselectivity. A molecular modelling study was carried out for understanding the structural determinants involved in the stereorecognition experimentally observed and unpredictable on the basis of steric properties of the substrates. As a result, a new useful catalyst was identified, enabling the enantioselective preparation of different aromatic alcohols and hydroxyketones.
- Contente, Martina Letizia,Serra, Immacolata,Brambilla, Marta,Eberini, Ivano,Gianazza, Elisabetta,De Vitis, Valerio,Molinari, Francesco,Zambelli, Paolo,Romano, Diego
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p. 193 - 201
(2016/01/09)
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- Ferrites catalyzed aerobic oxidation of benzoin and its extension to enantioselective version
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Ferrites have been used as efficient catalysts for the oxidation of α-hydroxy ketones in the presence of air. The enantio selective version of the benzoin oxidation gave 30% yield with 43% ee using (L)-tartaric acid as chiral modifier on magnetite (inverse spinel).
- Shaikh, Melad,Sahu, Mahendra,Gavel, Pramod K.,Ranganath, Kalluri V.S.
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- Reversibility of asymmetric catalyzed C-C bond formation by benzoylformate decarboxylase
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Benzoylformate decarboxylase (BFD) from Pseudomonas putida catalyzed the formation of 2-hydroxy-1-phenylpropanone (2-HPP), a 2-hydroxy ketone, from the kinetic resolution of rac-benzoin in the presence of acetaldehyde. The formation rate of 2-HPP via kinetic resolution of benzoin was 700-fold lower compared to the formation via direct carboligation of benzaldehyde and acetaldehyde. Further investigations revealed that BFD not only accepts (R)-benzoin but also 2-HPP as the substrate. A typical Michaelis-Menten type kinetics was observed starting from enantiopure (S)- or (R)-2-HPP. The formation of racemic 2-HPP while using benzoin as the donor in the presence of acetaldehyde and the racemization of (R/S)-2-HPP were detected. The equilibrium constant determined, showed favoured conditions towards the product side i.e. (R)-benzoin and 2-HPP. In the end, an extended reaction mechanism was proposed by supplementing the already known mechanism with the C-C bond cleavage activity of BFD towards 2-hydroxy ketones. This journal is
- Berheide, Marco,Kara, Selin,Liese, Andreas
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p. 2418 - 2426
(2015/04/14)
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- Synthesis and Enantioseparation Ability of Xylan Bisphenylcarbamate Derivatives as Chiral Stationary Phases in HPLC
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Ten novel xylan bisphenylcarbamate derivatives bearing meta- and para-substituents on their phenyl groups were synthesized and their chiral recognition abilities were evaluated as the chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) after coating them on macroporous silica. The chiral recognition abilities of these CSPs depended on the nature, position, and number of the substituents on the phenyl moieties. The introduction of an electron-donating group was more attractive than an electron-withdrawing group to improve the chiral recognition ability of the xylan phenylcarbamate derivatives. Among the CSPs discussed in this study, xylan bis(3,5-dimethylphenylcarbamate)-based CSP seems to possess the highest resolving power for many racemates, and the meta-substituted CSPs showed relatively better chiral recognition than the para-substituted ones. For some racemates, the xylan bis(3,5-dimethylphenylcarbamate) derivative exhibited higher enantioselectivity than the CSP based on cellulose tris(3,5-dimethylphenylcarbamate). Chirality 27:518-522, 2015
- Li, Geng,Shen, Jun,Li, Qiang,Okamoto, Yoshio
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p. 518 - 522
(2015/08/03)
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- Influence of Helical Structure on Chiral Recognition of Poly(phenylacetylene)s Bearing Phenylcarbamate Residues of L -Phenylglycinol and Amide Linage as Pendants
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Four poly(phenylacetylene)s (PPA-1, PPA-2, PPA-3, PPA-4) bearing phenylcarbamate residues of L-phenylglycinol and amide linkage as pendants were prepared to be used as chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC), and the influences of coating solvents, dimethylformamide (DMF) and tetrahydrofuran (THF), which were used for coating the polymers on silica gel, on the helical structure of the polymers and their chiral recognition abilities were investigated. The structure analysis of PPA-1, PPA-2, PPA-3, PPA-4 by 1H nuclear magnetic resonance (NMR), size exclusion chromatography (SEC), optical rotation, and circular dichroism (CD) spectra indicated that the polymers possess the cis-transoidal structure with dynamic helical conformation. The polymers in THF seem to have shorter conjugated helical main chains along with a tighter twist conformation than those in DMF. The chiral recognition abilities of PPA-1, PPA-2, PPA-3, PPA-4 with the different helical structures induced by the coating solvents were evaluated as the CSPs in HPLC. The helical structures of PPA-1, PPA-2, PPA-3, PPA-4 induced with THF are preferable for chiral recognition for some racemates compared to those induced with DMF, and higher chiral recognition abilities of PPA-1, PPA-2, PPA-3, PPA-4 were achieved using THF.
- Zhang, Chunhong,Ma, Rui,Wang, Hailun,Sakai, Ryosuke,Satoh, Toshifumi,Kakuchi, Toyoji,Liu, Lijia,Okamoto, Yoshio
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p. 500 - 506
(2015/08/03)
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- Synthesis and chiral recognition ability of a novel fullerene-functionalized cellulose derivative
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The fullerene-functionalized cellulose derivative 1 was synthesized and coated onto silica gel as chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC). The chiral recognition ability of the obtained chiral packing material (CPM) was evaluated by HPLC with ten types of racemates 2-11. This CPM could be used in the eluents including chloroform and terahydrofuran (THF), which are usually unsuitable solvents for conventional coating-type CPMs. Hence the scope of application of this CPM is wider than conventional coating CPM.
- Gao, Bo,Xu, Zeyu,Fan, Luan,Xu, Xiaodong,Bai, Jianwei,Shen, Xiande
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p. 1479 - 1481
(2015/11/24)
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- Regio- and enantioselective reduction of diketones: Preparation of enantiomerically pure hydroxy ketones catalysed by Candida parapsilosis ATCC 7330
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Enantiomerically enriched hydroxy ketones were prepared by the reduction of the corresponding diketones with excellent enantiomeric excess (98%) and in good yields (up to 75%) using whole cells of Candida parapsilosis ATCC 7330. Cyclic diketones, such as 1,2-cyclohexanedione and 1,4-cyclohexanedione, resulted in hydroxy ketones as products. Cyclohexane-1,3-dione and 5,5-dimethylcyclohexane-1,3-dione gave dimerised products, such as 2,2′-(ethane-1,1-diyl)bis(3-hydroxycyclohex-2-enone) and 2,2′-(ethane-1,1-diyl)bis(3-hydroxy-5,5-dimethylcyclohex-2-enone) with acetaldehyde generated in situ from whole cells of Candida parapsilosis ATCC 7330, which is reported here for the first time.
- Mahajabeen, Pula,Chadha, Anju
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p. 1167 - 1173
(2015/10/28)
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- Biocatalyzed asymmetric reduction of benzils to either benzoins or hydrobenzoins: pH dependent switch
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Enantiopure benzoins and hydrobenzoins are precursors of various pharmaceuticals and biologically active compounds. In addition, hydrobenzoins are precursors of chiral ligands and auxiliaries in stereoselective organic synthesis. Biocatalytic reduction of benzils is a straightforward approach to prepare these molecules. However, known methods are not selective and lead to formation of a mixture of benzoin and hydrobenzoin, requiring expensive separation procedures. Here, we describe an enzyme system Talaromyces flavus, which exhibited excellent pH dependent selectivity for the conversion of benzil to either benzoin or hydrobenzion in high ee. Thus, (S)-benzoin was the exclusive product at pH 5.0 (ee >99%), whereas at pH 7.0, (S,S)-hydrobenzoin (ee >99%, dl/meso 97 : 3) was the exclusive product. The observed pH dependent selectivity was shown to be due to the presence of multiple enzymes in Talaromyces flavus, which specifically accepted either benzil or benzoin as a substrate and exhibited different pH profiles of their activity. The biocatalyst efficiently reduced a variety of symmetrical and unsymmetrical benzils. Moreover, a 36.4 kDa benzoin reductase was purified, the N-terminal sequence of which did not show a significant similarity to any of the known reductase/dehydrogenase in the database. The protein therefore appears to be a novel reductase.
- Pal, Mohan,Srivastava, Gautam,Sharma, Amar Nath,Kaur, Suneet,Jolly, Ravinder S.
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p. 4017 - 4028
(2015/08/03)
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- Uridine, thymidine and inosine used as chiral stationary phases in HPLC
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In this paper, we present the first enantioseparations research using thymidine, uridine and inosine as chiral stationary phase bonded to silica gel via 3-(triethoxysilyl)propyl isocyanate in HPLC. Thymidine and uridine chiral stationary phases possess enantioseparation selectivity for alcohols, amines, ketones and carboxylic acids to some degree in normal-phase and reversed-phase mode. This work indicates that nucleoside or deoxynucleoside can be useful for the separation of enantiomers in the liquid phase as a new kind of chiral stationary phase.
- Zhang, Mei,Zi, Min,Wang, Bang-Jin,Yuan, Li-Ming
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p. 2226 - 2228
(2014/06/09)
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- Enantioselective oxidation of 1,2-diols with quinine-derived urea organocatalyst
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Quinine-derived urea has been identified as a highly efficient organocatalyst for the enantioselective oxidation of 1,2-diols using bromination reagents as the oxidant. This simple procedure utilizes readily available reagents and operates at ambient temperature to yield a wide range of α-hydroxy ketones in good yield (up to 94%) and excellent enantioselectivity (up to 95% ee).
- Rong, Zi-Qiang,Pan, Hui-Jie,Yan, Hai-Long,Zhao, Yu
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p. 208 - 211
(2014/01/23)
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- A tailor-made chimeric thiamine diphosphate dependent enzyme for the direct asymmetric synthesis of (S)-benzoins
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Thiamine diphosphate dependent enzymes are well known for catalyzing the asymmetric synthesis of chiral α-hydroxy ketones from simple prochiral substrates. The steric and chemical properties of the enzyme active site define the product spectrum. Enzymes catalyzing the carboligation of aromatic aldehydes to (S)-benzoins have not so far been identified. We were able to close this gap by constructing a chimeric enzyme, which catalyzes the synthesis of various (S)-benzoins with excellent enantiomeric excess (>99) and very good conversion. Hybrid vigor: Combining the active-site characteristics of two thiamine diphosphate (ThDP) dependent enzymes solved the long-standing problem of enzymatic asymmetric (S)-benzoin synthesis starting from commercially available benzaldehydes. The resulting rationally designed hybrid enzyme provides access to various (S)-benzoins with excellent enantiomeric excess and good conversion.
- Westphal, Robert,Vogel, Constantin,Schmitz, Carlo,Pleiss, Jürgen,Müller, Michael,Pohl, Martina,Rother, D?rte
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supporting information
p. 9376 - 9379
(2014/09/17)
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- Synthesis of new chiral keto alcohols by baker's yeast
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Fourteen chiral α- and β-keto alcohols 2a-2r were synthesized by the asymmetric reduction of their corresponding diketones 1a-1r via baker's yeast. In addition, ten corresponding racemic α-keto alcohols were synthesized by the benzoin condensation of their corresponding aldehydes, which were used for the determination of the ee values through their chiral resolution on chiral HPLC. Amongst the 15 diketones, 1j and chiral α-keto alcohols 2i, 2j and chiral β-keto alcohol 2r are novel compounds. Six keto alcohols 2b, 2c, 2d, 2f, 2h and 2p were synthesized by baker's yeast for the first time. There are some studies in the literature where baker's yeast was applied to the diketones 1a, 1g, 1e, 1k and 1n under various conditions different to those reported herein. The yields and the ee values of these studies were not as high as ours. All of the keto alcohols synthesized were characterized by IR, NMR (1H and 13C), and MS. The relationship between the structure of the diketone and the yield, diastereoselectivity and enantiomeric excess is also discussed.
- Yildiz, Tuelay,Canta, Nurguel,Yusufoglu, Ayse
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p. 340 - 347
(2014/04/03)
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- Readily available ruthenium complex for efficient dynamic kinetic resolution of aromatic α-hydroxy ketones
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A ruthenium complex formed from commercially available [Ru(p-cymene)Cl 2]2 and 1,4-bis(diphenylphosphino)butane catalyzes the racemization of aromatic α-hydroxy ketones very efficiently at room temperature. The racemization is fully compatible with a kinetic resolution catalyzed by a lipase from Pseudomonas stutzeri. This is the first example of dynamic kinetic resolution of α-hydroxy ketones at ambient temperature in which the metal and enzyme catalysts work in concert in one pot at room temperature to give quantitative yields of esters of α-hydroxy ketones with very high enantioselectivity.
- Agrawal, Santosh,Martinez-Castro, Elisa,Marcos, Rocio,Martin-Matute, Belen
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p. 2256 - 2259
(2014/05/06)
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- Regio- and enantio-selective oxidation of diols by Candida parapsilosis ATCC 7330
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Selectivity between primary and secondary alcohols was observed in oxidation using whole cells of Candida parapsilosis ATCC 7330, where the secondary alcohol was preferentially oxidized. In racemic sec alcohols, the 'R' enantiomer was selectively oxidized to the corresponding keto alcohol (yield = 18-54%) leaving the 'S' diol (yield = 31-69% and enantiomeric excess from 14% to >99%). A biphasic system consisting of isooctane-water (48 : 2 v/v) was used as a medium for biotransformation at 25 °C. This is the first report of the regio- and enantio-selective oxidation of diols using C. parapsilosis ATCC 7330.
- Sivakumari, Thakkellapati,Chadha, Anju
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p. 60526 - 60533
(2015/02/19)
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