134562-59-7Relevant articles and documents
A High-Throughput Screening Method for the Directed Evolution of Hydroxynitrile Lyase towards Cyanohydrin Synthesis
Zheng, Yu-Cong,Ding, Liang-Yi,Jia, Qiao,Lin, Zuming,Hong, Ran,Yu, Hui-Lei,Xu, Jian-He
, p. 996 - 1000 (2021/01/15)
Chiral cyanohydrins are useful intermediates in the pharmaceutical and agricultural industries. In nature, hydroxynitrile lyases (HNLs) are a kind of elegant tool for enantioselective hydrocyanation of carbonyl compounds. However, currently available methods for demonstrating hydrocyanation are still stalled at precise, but low-throughput, GC or HPLC analyses. Herein, we report a chromogenic high-throughput screening (HTS) method that is feasible for the cyanohydrin synthesis reaction. This method was highly anti-interference and sensitive, and could be used to directly profile the substrate scope of HNLs either in cell-free extract or fermentation clear broth. This HTS method was also validated by generating new variants of PcHNL5 that presented higher catalytic efficiency and stronger acidic tolerance in variant libraries.
Stabilization of Hydroxynitrile Lyases from Two Variants of Passion Fruit, Passiflora edulis Sims and Passiflora edulis Forma flavicarpa, by C-Terminal Truncation
Nuylert, Aem,Motojima, Fumihiro,Khanongnuch, Chartchai,Hongpattarakere, Tipparat,Asano, Yasuhisa
, p. 181 - 189 (2019/12/12)
Because the synthesis of chiral compounds generally requires a broad range of substrate specificity and stable enzymes, screening for better enzymes and/or improvement of enzyme properties through molecular approaches is necessary for sustainable industri
Supported Ionic Liquid-Like Phases (SILLPs) as Immobilised Catalysts for the Multistep and Multicatalytic Continuous Flow Synthesis of Chiral Cyanohydrins
Peris, Edgar,Porcar, Raúl,Burguete, María Isabel,García-Verdugo, Eduardo,Luis, Santiago V.
, p. 1955 - 1962 (2019/03/13)
Supported Ionic Liquid-Like Phases have been found to be efficient organocatalysts for the synthesis of cyanohydrin esters under solvent-free conditions by an “electrophile-nucleophile dual activation” based on hydrogen bond formation. The combination of
Controlled Exchange of Achiral Linkers with Chiral Linkers in Zr-Based UiO-68 Metal-Organic Framework
Tan, Chunxia,Han, Xing,Li, Zijian,Liu, Yan,Cui, Yong
supporting information, p. 16229 - 16236 (2018/11/27)
The development of highly robust heterogeneous catalysts for broad asymmetric reactions has always been a subject of interest, but it remains a synthetic challenge. Here we demonstrated that highly stable metal-organic frameworks (MOFs) with potentially acid-labile chiral catalysts can be synthesized via postsynthetic exchange. Through a one- or two-step ligand exchange, a series of asymmetric metallosalen catalysts with the same or different metal centers are incorporated into a Zr-based UiO-68 MOF to form single- and mixed-M(salen) linker crystals, which cannot be accomplished by direct solvothermal synthesis. The resulting MOFs have been characterized by a variety of techniques including single-crystal X-ray diffraction, N2 sorption, CD, and SEM/TEM-EDS mapping. The single-M(salen) linker MOFs are active and efficient catalysts for asymmetric cyanosilylation of aldehydes, ring-opening of epoxides, oxidative kinetic resolution of secondary alcohols, and aminolysis of stilbene oxide, and the mixed-M(salen) linker variants are active for sequential asymmetric alkene epoxidation/epoxide ring-opening reactions. The chiral MOF catalysts are highly enantioselective and completely heterogeneous and recyclable, making them attractive catalysts for eco-friendly synthesis of fine chemicals. This work not only advances UiO-type MOFs as a new platform for heterogeneous asymmetric catalysis in a variety of syntheses but also provides an attractive strategy for designing robust and versatile heterogeneous catalysts.
Hydroxynitrile Lyase Isozymes from Prunus communis: Identification, Characterization and Synthetic Applications
Zheng, Yu-Cong,Xu, Jian-He,Wang, Hui,Lin, Guo-Qiang,Hong, Ran,Yu, Hui-Lei
supporting information, p. 1185 - 1193 (2017/04/13)
Biocatalysts originating from Badamu (Prunus communis) have been applied to catalyze the asymmetric synthesis of (R)-4-methylsulfanylmandelonitrile, a key building block of thiamphenicol and florfenicol. Here, four hydroxynitrile lyase (HNL) isozymes from Badamu were cloned and heterologously expressed in Pichia pastoris. The biochemical properties and catalytic performances of these isozymes were comprehensively explored to evaluate their efficiency and selectivity in asymmetric synthesis. Among then, PcHNL5 was identified with outstanding activity and enantioselectivity in asymmetric hydrocyanation. Under the optimized mild biphasic reaction conditions, seventeen prochiral aromatic aldehydes were converted to valuable chiral cyanohydrins with good yields (up to 94%) and excellent optical purities (up to >99.9% ee), which provide a facile access to numerous chiral amino alcohols, hypoglycemic agents, angiotension converting enzyme (ACE) inhibitors and β-blockers. This work therefore underlines the importance of discovering the most potent biocatalyst among a group of isozymes for converting unnatural substrates into value-added products. (Figure presented.).
Discovery and molecular and biocatalytic properties of hydroxynitrile lyase from an invasive millipede, Chamberlinius hualienensis
Dadashipour, Mohammad,Ishida, Yuko,Yamamoto, Kazunori,Asano, Yasuhisa
, p. 10605 - 10610 (2015/09/07)
Hydroxynitrile lyase (HNL) catalyzes the degradation of cyanohy-drins and causes the release of hydrogen cyanide (cyanogenesis). HNL can enantioselectively produce cyanohydrins, which are valuable building blocks for the synthesis of fine chemicals and ph
Chemoenzymatic asymmetric synthesis of fluoxetine, atomoxetine, nisoxetine, and duloxetine
Rej, Rohan Kalyan,Das, Tapas,Hazra, Suman,Nanda, Samik
, p. 913 - 918 (2013/09/23)
The asymmetric synthesis of two well-known anti-depressant drugs, fluoxetine and duloxetine has been accomplished in a chemoenzymatic manner. The main highlight of the synthesis is the enantioselective cyanohydrin formation by a plant (R)-HNL (hydroxynitrile lyase). The enantiopure cyanohydrins are then synthetically manipulated into the above two drug molecules and two of their structural analogues, atomoxetine and nisoxetine.
Purification and characterization of a novel (R)-hydroxynitrile lyase from Eriobotrya japonica (Loquat)
Ueatrongchit, Techawaree,Kayo, Ai,Komeda, Hidenobu,Asano, Yasuhisa,H-Kittikun, Aran
, p. 1513 - 1522 (2008/12/21)
A hydroxynitrile lyase was isolated and purified to homogeneity from seeds of Eriobotrya japonica (loquat). The final yield, of 36% with 49-fold purification, was obtained by 30-80% (NH4)2SO4 fractionation and column chromatography on DEAE-Toyopearl and Concanavalin A Sepharose 4B, which suggested the presence of a carbohydrate side chain. The purified enzyme was a monomer with a molecular mass of 72 kDa as determined by gel filtration, and 62.3 kDa as determined by SDS-gel electrophoresis. The N-terminal sequence is reported. The enzyme was a flavoprotein containing FAD as a prosthetic group, and it exhibited a Km of 161 μM and a k cat/Km of 348 s-1 mM-1 for mandelonitrile. The optimum pH and temperature were pH 5.5 and 40°C respectively. The enzyme showed excellent stability with regard to pH and temperature. Metal ions were not required for its activity, while activity was significantly inhibited by CuSO4, HgCl2, AgNO3, FeCl3, β-mercaptoethanol, iodoacetic acid, phenylmethylsulfonylfluoride, and diethylpyrocarbonate. The specificity constant (kcat/Km) of the enzyme was investigated for the first time using various aldehydes as substrates. The enzyme was active toward aromatic and aliphatic aldehydes, and showed a preference for smaller substrates over bulky one.
A new (R)-hydroxynitrile lyase from Prunus mume: Asymmetric synthesis of cyanohydrins
Nanda, Samik,Kato, Yasuo,Asano, Yasuhisa
, p. 10908 - 10916 (2007/10/03)
A new hydroxynitrile lyase (HNL) was isolated from the seed of Japanese apricot (Prunus mume). The enzyme has similar properties with HNL isolated from other Prunus species and is FAD containing enzyme. It accepts a large number of unnatural substrates (benzaldehyde and its variant) for the addition of HCN to produce the corresponding cyanohydrins in excellent optical and chemical yields. A new HPLC based enantioselective assay technique was developed for the enzyme, which promotes the addition of KCN to benzaldehyde in a buffered solution (pH=4.5).
A practical high through-put continuous process for the synthesis of chiral cyanohydrins
Chen, Peiran,Han, Shiqing,Lin, Guoqiang,Li, Zuyi
, p. 8251 - 8253 (2007/10/03)
A practical high through-put continuous process for the synthesis of chiral cyanohydrins is reported. Pretreated almond meal (or other solid raw enzyme sources) was loaded in a column to form a reactor, to which were attached a supplying system to deliver
