- Approach to (R)- and (S)-ketone cyanohydrins using almond and apple meal as the source of (R)-oxynitrilase
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The synthesis of aliphatic and aromatic (R)-ketone cyanohydrins through the addition of hydrogen cyanide to the corresponding ketones and the synthesis of the (S)-enantiomers through the kinetic resolution of racemic ketone cyanohydrins has been studied in the presence of almond or apple meal. Substrate tolerance of the (R)-oxynitrilases towards ketones (R1R2C=O) is highly restricted compared to that of structurally similar aldehydes, reactivity following the order of H>Me>>Et for R2. In the case of aromatic methyl ketones reactivity difference (C6H5>>p-Me-C6H4 for R1) is notable.
- Kiljunen, Eero,Kanerva, Liisa T.
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- A High-Throughput Screening Method for the Directed Evolution of Hydroxynitrile Lyase towards Cyanohydrin Synthesis
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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.
- Zheng, Yu-Cong,Ding, Liang-Yi,Jia, Qiao,Lin, Zuming,Hong, Ran,Yu, Hui-Lei,Xu, Jian-He
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p. 996 - 1000
(2021/01/15)
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- Fusion of a Coiled-Coil Domain Facilitates the High-Level Production of Catalytically Active Enzyme Inclusion Bodies
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The increasing number of biocatalytic reactions implemented in chemical synthesis routes raises the urgent need for large amounts of enzymes. Hence, new generic methods are required for their simple and cost-efficient production. Here, we describe a gener
- Diener, Martin,Kopka, Benita,Pohl, Martina,Jaeger, Karl-Erich,Krauss, Ulrich
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p. 142 - 152
(2016/01/25)
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- Chemoenzymatic asymmetric total synthesis of nonanolide (Z)-cytospolides D, E and their stereoisomers
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Chemoenzymatic asymmetric total synthesis of the (Z)-isomer of the naturally occurring decanolide cytospolides D, E and six stereoisomers is reported. The main highlight of the synthetic venture involves ring-closing metathesis (RCM) reaction of a suitably functionalized ester compound, which was assembled by the Yamaguchi coupling of the required acid and alcohol fragments. The alcohol fragment was ac- cessed by two alternative chemoenzymatic processes, one being hydroxynitrile lyase mediated hydrocyanation, whereas lipase-catalyzed transesterification was the key sep in the second route. The acid fragment was constructed by an enantioselective enzymatic desymmetrization (EED) of prochiral 2-methyl-1,3-propanediol and Corey-Bakshi-Shibata (CBS) mediated stereoselective carbonyl reduction.
- Rej, Rohan Kalyan,Nanda, Samik
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p. 860 - 871
(2014/03/21)
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- Chemoenzymatic Asymmetric Total Synthesis of Nonanolide (Z)-Cytospolides D, e and Their Stereoisomers
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Chemoenzymatic asymmetric total synthesis of the (Z)-isomer of the naturally occurring decanolide cytospolides D, E and six stereoisomers is reported. The main highlight of the synthetic venture involves ring-closing metathesis (RCM) reaction of a suitably functionalized ester compound, which was assembled by the Yamaguchi coupling of the required acid and alcohol fragments. The alcohol fragment was accessed by two alternative chemoenzymatic processes, one being hydroxynitrile lyase mediated hydrocyanation, whereas lipase-catalyzed transesterification was the key sep in the second route. The acid fragment was constructed by an enantioselective enzymatic desymmetrization (EED) of prochiral 2-methyl-1,3-propanediol and Corey-Bakshi-Shibata (CBS) mediated stereoselective carbonyl reduction.
- Rej, Rohan Kalyan,Nanda, Samik
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p. 860 - 871
(2015/10/05)
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- Enantioselective cyanosilylation of aldehydes catalyzed by novel camphor derived Schiff bases-titanium(IV) complexes
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Five tridentate Schiff bases have been prepared from (1R,2S,3R,4S)-3-amino- 1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol and salicylaldehydes. X-ray structure investigation revealed differences in their molecular conformation, and their titanium(IV) complexes
- B?ocka, Ewelina,Bosiak, Mariusz J.,We?niak, Miros?aw,Ludwiczak, Agnieszka,Wojtczak, Andrzej
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p. 554 - 562
(2014/05/06)
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- Hydroxynitrile lyase from Arabidopsis thaliana: Identification of reaction parameters for enantiopure cyanohydrin synthesis by pure and immobilized catalyst
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The (R)-selective hydroxynitrile lyase from Arabidopsis thaliana (AtHNL) is a promising biocatalyst for the synthesis of a broad range of chiral cyanohydrins. However, the enantiomeric excess of the reaction is strongly compromised by a non-catalyzed side
- Okrob, Daniel,Paravidino, Monica,Orru, Romano V. A.,Wiechert, Wolfgang,Hanefeld, Ulf,Pohl, Martina
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experimental part
p. 2399 - 2408
(2011/11/06)
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- α-Pinene-type chiral Schiff bases as tridentate ligands in asymmetric addition reactions
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A group of tridentate Schiff bases derived from (+)-α-pinene were synthesized. The steric effects in the transition state, the importance of π-π stacking interactions as well as the electronic effects of aryl aldehydes according to Hammett constant values in the enantioselective addition of Et2Zn to aldehydes with the use of Schiff bases as chiral ligands are described. Also, a variety of aldehydes were cyanated using a catalyst prepared in situ from titanium tetraisopropoxide and chiral Schiff bases. The influence of a conjugated double-bond in the cyanation substrates on enantioselectivity was observed. The chemical structures of the chiral Schiff base-titanium alkoxide complexes are discussed based on their 1H and 13C NMR spectra. 3D models of the Zn2-complex catalyst and Ti-complex catalyst containing α-pinane-type Schiff bases based on X-ray diffraction experiments are postulated. The models presented were consistent with the reported chirality of the addition product and observed ee.
- Jaworska, Magdalena,Blocka, Ewelina,Kozakiewicz, Anna,Welniak, Miroslaw
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experimental part
p. 648 - 657
(2011/07/08)
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- Enantioselective silylcyanation of aldehydes catalyzed by new chiral oxovanadium complex
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Oxovanadium(V) complex 4 was prepared from VOSO4 and tridentate Schiff base ligand, which was prepared from substituted salicylaldehyde and inexpensive (S)-valine. Asymmetric silylcyanation of the aldehydes catalyzed by catalyst 4 afforded cyanohydrins with good enantioselectivities.
- Chu, Chang-Ying,Hsu, Chu-Tin,Lo, Po Hsiang,Uang, Biing-Jiun
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scheme or table
p. 1981 - 1984
(2012/03/10)
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- An R-selective hydroxynitrile lyase from Arabidopsis thaliana with an α/β-hydrolase fold
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Folding and selectivity: The noncyanogenic plant Arabidopsis thaliana contains a new hydroxynitrile lyase, which was cloned and characterized. This enzyme is readily available form a recombinant source, has a broad range of substrates, and enantioselectively transforms aliphatic and aromatic aldehydes as well as ketones into the corresponding R-cyanohydrins. (Chemical Equation Presented).
- Andexer, Jennifer,Von Langermann, Jan,Mell, Annett,Bocola, Marco,Kragl, Udo,Eggert, Thorsten,Pohl, Martina
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p. 8679 - 8681
(2008/09/18)
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- Immobilized hydroxynitrile lyases for enantioselective synthesis of cyanohydrins: Sol-gels and cross-linked enzyme aggregates
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The hydroxynitrile lyases (HNLs) from Prunus amygdalus (paHNL), Manihot esculenta (MeHNL), and Hevea brasiliensis (HbHNL) were successfully immobilized in sol-gels. The cross-linked enzyme aggregate (CLEA) of HbHNL was also prepared. These immobilized enzymes and the commercial PaHNL- and MeHNL-CLEAs were employed for the enantioselective synthesis of cyanohydrins. The sol-gels were highly efficient at low catalyst loading and particularly stable towards the organic solvent (diisopropyl ether) and substrate/product deactivation. The stabilization effect was inconsistent for CLEAs of different HNLs and significant deactivation of PaHNL- and HbHNL-CLEAs in diisopropyl ether was observed. In contrast commercial MeHNL-CLEA proved to be a remarkably robust and efficient biocatalyst in diisopropyl ether.
- Cabirol, Fabien L.,Hanefeld, Ulf,Sheldon, Roger A.
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p. 1645 - 1654
(2007/10/03)
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- The first encapsulation of hydroxynitrile lyase from Hevea brasiliensis in a sol-gel matrix
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A straightforward process for the encapsulation of HbHNL under low methanol conditions has been developed. By adding a sol, prepared by hydrolysis of TMOS/MTMS at pH 2.8 with continuous removal of methanol, to a stirred solution of the enzyme in a buffer at pH 6.5, at least 65% of the activity of the free enzyme could be recovered after the encapsulation. The aquagels were successfully used in the synthesis of (S)-cyanohydrins. Graphical Abstract.
- Veum, Lars,Hanefeld, Ulf,Pierre, Alain
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p. 10419 - 10425
(2007/10/03)
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- Enzyme catalysed formation of (S)-cyanohydrins derived from aldehydes and ketones in a biphasic solvent system
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By employing a vigorously stirred two phase system aqueous buffer/organic solvent and using the hydroxynitrile lyase from Hevea brasiliensis as biocatalyst enantiopure (S)-cyanohydrins from aliphatic, unsaturated, aromatic and heteroaromatic aldehydes and methyl alkyl and methyl phenyl ketones are obtained in high yield and in general 98-99% enantiomeric excess.
- Griengl, Herfried,Klempier, Norbert,Poechlauer, Peter,Schmidt, Michael,Shi, Nongyuan,Zabelinskaja-Mackova, Antonina A.
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p. 14477 - 14486
(2007/10/03)
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- Novel (R)-oxynitrilase sources for the synthesis of (R)-cyanohydrins in diisopropyl ether
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Apple, apricot, cherry and plum meal were prepared from the seeds or kernels of mature garden fruits. The preparations as well as almond meal were used as the source of (R)-oxynitrilase for the synthesis of aliphatic and aromatic cyanohydrins in diisoprop
- Kiljunen, Eero,Kanerva, Liisa T.
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p. 1225 - 1234
(2007/10/03)
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- Sulfoximine-titanium reagents in enantioselective trimethylsilylcyanations of aldehydes
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Chiral titanium reagents derived from optically active sulfoximines and Ti(O-i-Pr)4 promote the asymmetric addition of trimethysilyl cyanide to aldehydes affording cyanohydrins in high yields with good enantioselectivities (up to 91% ee). The ligand structure and the reaction conditions have been optimized. With substoichiometric amounts of the sulfoximine-titanium reagent the product is obtained in decreased yield with lower enantiomeric excess. The molecular structures of (R)-S-(2-hydroxypheny)-S-methyl sulfoximine [(R)-4a] and (R)-S-(2-hydroxyphenyl)-S-(1.1-dimethylethyl) sulioximine [(R)-4d) have been determined by X-ray diffraction analysis. Acta Chemica Scandinavica 1996.
- Bolm, Garsten,Mueller, Peter,Harms, Klaus
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p. 305 - 315
(2007/10/03)
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- Enantioselective trimethylsilylcyanation of aldehydes
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A chiral titanium reagent derived from optically active sulfoximine (R)-3 and Ti(O-i-Pr)4 promotes the asymmetric addition of trimethylsilylcyanide to aldehydes affording cyanohydrins in high yields with good enantioselectivities (up to 91% ee).
- Bolm, Carsten,Mueller, Peter
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p. 1625 - 1628
(2007/10/02)
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- Aliphatic (S)-Cyanohydrins by Enzyme Catalyzed Synthesis
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The enzyme catalyzed synthesis of aliphatic (S)-cyanohydrins has been accomplished for the first time by application of a hydroxynitrile lyase from leaves of Hevea brasiliensis.The optical purities of (S)-cyanohydrins obtained are in a range between 60 - 97percent.
- Klempier, Norbert,Griengl, Herfried,Hayn, Marianne
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p. 4769 - 4772
(2007/10/02)
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- Enzymatic Resolution of Optically Active Aliphatic Cyanohydrins
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Enantioselective acylation of cyanohydrins 1a-9a by PPL catalysis and deacylation of propionates 1b-9b by CCL catalysis in toluene from good (E 15-20) to excellent (E >30) enantioselectivity.A solvent has a clear effect on enzymatic enantioselectivity.
- Kanerva, Liisa T.,Kiljunen, Eero,Huuhtanen, Tuomas T.
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p. 2355 - 2362
(2007/10/02)
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- Enzyme-Catalysed Synthesis of Optically Active Aliphatic Cyanohydrins
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The enantioselective preparation of aliphatic (R)-cyanohydrins was studied using powdered almond meal, a rich source of mandelonitrile lyase, as a catalyst in organic solvent.The feasibility of powdered almond meal as a catalyst was compared to that of a purified enzyme preparation.
- Huuhtanen, Tuomas T.,Kanerva, Liisa T.
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p. 1223 - 1226
(2007/10/02)
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- Cyclo-((S)-leucyl-(S)-histidyl). A Catalyst for Asymmetric Addition of Hydrogen Cyanide to Aldehydes
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Asymmetric addition of hydrogen cyanide to various aldehydes in the presence of a catalytic amount of cyclo-((S)-leucyl-(S)-histidyl) affords the corresponding cyanohydrins in moderate to good optical yields.The reaction of benzaldehyde with hydrogen cyanide gives (S)-2-hydroxy-2-phenylacetonitrile (85percent, 55percent ee) whose stereochemistry is found to be opposite to our previous result using cyclo-((S)-phenylalanyl-(S)-histidyl).
- Mori, Atsunori,Ikeda, Yoshitaka,Kinoshita, Koichi,Inoue, Shohei
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p. 2119 - 2122
(2007/10/02)
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