- 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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Read Online
- Large-scale synthesis of (R)-2-amino-1-(2-furyl)ethanol via a chemoenzymatic approach
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A two-step chemoenzymatic synthesis of (R)-2-amino-1-(2-furyl)ethanol for laboratory production was developed followed by successful up-scaling to kilogram scale. The generation of the asymmetric centre was accomplished by a highly enantioselective cyanohydrin reaction of furan-2-carbaldehyde with hydrocyanic acid catalyzed by the hydroxynitrile lyase from Hevea brasiliensis. Subsequent sodium borohydride reduction furnished the desired product with an enantiomeric excess of higher than 99.5%. This procedure can be considered a convenient general route for the stereoselective synthesis of ethanol amine derivatives underlining the role of biocatalysis for the generation of stereogenic centres in the synthesis of chiral intermediates.
- Purkarthofer, Thomas,Pabst, Thomas,Van Den Broek, Cor,Griengl, Herfried,Maurer, Oliver,Skranc, Wolfgang
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Read Online
- Stabilization of Hydroxynitrile Lyases from Two Variants of Passion Fruit, Passiflora edulis Sims and Passiflora edulis Forma flavicarpa, by C-Terminal Truncation
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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
- Nuylert, Aem,Motojima, Fumihiro,Khanongnuch, Chartchai,Hongpattarakere, Tipparat,Asano, Yasuhisa
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p. 181 - 189
(2019/12/12)
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- Hydroxynitrile Lyase Isozymes from Prunus communis: Identification, Characterization and Synthetic Applications
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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.).
- Zheng, Yu-Cong,Xu, Jian-He,Wang, Hui,Lin, Guo-Qiang,Hong, Ran,Yu, Hui-Lei
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supporting information
p. 1185 - 1193
(2017/04/13)
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- High-Throughput Preparation of Optically Active Cyanohydrins Mediated by Lipases
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Cyanohydrins are versatile compounds with high applicability in organic synthesis; they are used as starting materials for the synthesis of other chemical targets with high industrial added value. Lipase-mediated kinetic resolution reactions are a promising route for the synthesis of optically active cyanohydrins. These reactions can be carried out through the acylation of cyanohydrins or the deacylation of cyanohydrin esters, with different biocatalysts and under different reaction conditions. Unfortunately, depending on the substrate structure, long reaction times can be required to achieve suitable enantiomeric excesses. In this context, we present a high-throughput protocol for the production of optically active cyanohydrins in continuous-flow mode. The products were obtained with moderate to good enantioselectivity (E values from 8 up to >200) and with productivity values from 2.4 to 8.7 times higher in continuous-flow mode than in batch mode. Moreover, the reaction times were reduced from hours in batch mode to minutes in continuous-flow mode.
- Thomas, Juliana Christina,Aggio, Bruno Bernardi,Marques de Oliveira, Alfredo Ricardo,Piovan, Leandro
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p. 5964 - 5970
(2016/12/26)
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- An orthogonal biocatalytic approach for the safe generation and use of HCN in a multistep continuous preparation of chiral O-acetylcyanohydrins
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An enantioselective preparation of O-acetylcyanohydrins has been accomplished by a three-step telescoped continuous process. The modular components enabled an accurate control of two sequential biotransformations, safe handling of an in situ generated hazardous gas, and in-line stabilization of products. This method proved to be advantageous over the batch protocols in terms of reaction time (40 min vs 345 min) and ease of operation, opening up access to reactions which have often been neglected due to safety concerns.
- Brahma, Aischarya,Musio, Biagia,Ismayilova, Uliviya,Nikbin, Nikzad,Kamptmann, Sonja B.,Siegert, Petra,Jeromin, Günter E.,Ley, Steven V.,Pohl, Martina
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supporting information
p. 262 - 266
(2016/01/20)
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- Chemoenzymatic flow cascade for the synthesis of protected mandelonitrile derivatives
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A chemoenzymatic two-step cascade process, with both steps having incompatible reaction conditions, was successfully performed in continuous flow. The chemoenzymatic aqueous formation of cyanohydrins was integrated with a subsequent organic phase protection step in a single flow process utilising a membrane-based phase separation module. The wider applicability of our setup was demonstrated with the synthesis of nine protected cyanohydrin derivatives, all obtained in good yields and high to excellent enantioselectivity.
- Delville, Marille M. E.,Koch, Kaspar,Van Hest, Jan C. M.,Rutjes, Floris P. J. T.
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supporting information
p. 1634 - 1638
(2015/03/05)
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- Improving the properties of bacterial r-selective hydroxynitrile lyases for industrial applications
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Hydroxynitrile lyases (HNLs) catalyse the reversible cleavage of cyanohydrins to carbonyl compounds and HCN. The recent discovery of bacterial HNLs with a cupin fold gave rise to a new promising class of these enzymes. They are interesting candidates for the synthesis of cyanohydrins on an industrial scale owing to their high expression levels in Escherichia coli. The activity and enantioselectivity of the manganese-dependent HNL from Granulicella tundricola (GtHNL) were significantly improved by site-saturation mutagenesis of active site amino acids. The combination of beneficial mutations resulted in a variant with 490-fold higher specific activity in comparison to the wild-type enzyme. More importantly, GtHNL-A40H/V42T/Q110H is a highly competitive alternative for the synthesis of chiral cyanohydrins, such as 2-chlorobenzaldehyde cyanohydrin, (R)-2-hydroxy-4-phenylbutyronitrile, and (R)-2-hydroxy-4-phenyl-3-butene nitrile, which serve as intermediates for the synthesis of pharmaceuticals.
- Wiedner, Romana,Kothbauer, Bettina,Pavkov-Keller, Tea,Gruber-Khadjawi, Mandana,Gruber, Karl,Schwab, Helmut,Steiner, Kerstin
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p. 325 - 332
(2015/03/05)
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- (R)-selective hydroxynitrile lyase variants with a cupin fold having improved substrate scope and the use thereof
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The present invention relates to an improved recombinant cupin-hydroxynitrile lyase (HNL), which is capable to catalyze the asymmetric cyanohydrin reaction, wherein the recombinant cupin-HNL comprises at least one amino acid substitution, preferably at le
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Paragraph 0082; 0083
(2015/12/31)
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- A simple separation method for (S)-hydroxynitrile lyase from cassava and its application in asymmetric cyanohydrination
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Using an acetone precipitation method, crude (S)-hydroxynitrile lyase [(S)-MeHNL] was separated from Munihot esculenta (cassava) leaves, and used directly as biocatalyst to catalyze asymmetric cyanohydrination and produce cyanohydrins with enantiomeric purities (≥90% ee) significantly greater than those previously reported. The use of a water/i-Pr2O system with an enzyme, NaCN, and appropriate amounts of acetic acid is crucial in improving the stereoselectivity of cyanohydrin formation by minimizing the non-enzymatic reaction and the racemization of the chiral products. The proposed isolation method for crude (S)-MeHNL has a high value because of its simplicity, and low cost as well as the high activity of the crude (S)-MeHNL.
- Zheng, Zubiao,Zi, Yan,Li, Zhongzhou,Zou, Xinzhuo
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p. 434 - 439
(2013/06/27)
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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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- Unsymmetric salen ligands bearing a Lewis base: Intramolecularly cooperative catalysis for cyanosilylation of aldehydes
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A series of unsymmetric salen ligands derived from 1,2-diaminocyclohexane bearing an appended Lewis base on the three-position of one aromatic ring were synthesized by the reaction of various functional salicyaldehydes with the condensation product of 1,2-diaminocyclohexane mono(hydrogen chloride) and 3,5-di-tert-butylsalicylaldehyde. These ligands in conjunction with Ti(O iPr)4 exhibited excellent activity in catalyzing the cyanosilylation of aldehydes with trimethylsilyl cyanide (TMSCN) at mild conditions. The highest activity was observed in the catalyst system with regard to the salen ligand bearing a diethylamino group, which proved to be active even at a high [aldehyde]/[catalyst] ratio up to 50000. In a low catalyst loading of 0.05 mol%, the quantitative conversion of benzaldehyde to the corresponding cyanosilylation product was found within 10 min. at ambient temperature. An intramolecularly cooperative catalysis was proposed wherein the central metal Ti(iv) is suggested to play a role of Lewis acid to activate aldehydes while the appended Lewis base to activate TMSCN.
- Wen, Ye-Qian,Ren, Wei-Min,Lu, Xiao-Bing
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supporting information; experimental part
p. 6323 - 6330
(2011/10/09)
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- Highly active bifunctional salenTi(IV) catalysts for asymmetric cyanosilylation of aldehydes and TMSCN
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A novel enantiopure salen ligand bearing a diphenylphosphine oxide on the 3-position of one aromatic ring was synthesized and combined with Ti(Oi-Pr) 4 as a monometallic bifunctional catalyst for asymmetric cyanosilylation reaction of aldehydes with trimethylsilyl cyanide (TMSCN). The catalyst system exhibited excellent activity and moderate enantioselectivity. The addition of TMSCN to 4-nitrobenzaldehyde in the presence of 1 mol% catalyst loading could complete within 10 min at ambient temperature. An intramolecularly cooperative catalysis was observed in this system wherein the central metal Ti(IV) is suggested to play a role of Lewis acid to activate aldehydes while the appended diphenylphosphine oxide worked as Lewis base to activate TMSCN.
- Wen, Ye Qian,Ren, Wei Min,Lu, Xiao Bing
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scheme or table
p. 1285 - 1288
(2012/01/17)
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- A novel bifunctional Ti(IV) complex catalyzed asymmetric silylcyanation of aldehydes
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A novel Lewis acid and Lewis base bifunctional Ti(IV) complex was formed in situ upon the treatment of ligand (R)-3,3′-bis(diphenylphosphinoyl)-BINOL with Ti(PrO-i)4, which is proven to be an efficient catalyst in the asymmetric trimethylsilylc
- Tang, Hongying,Zhang, Zhongbiao
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- A novel chiral (salen)AlIII complex catalyzed asymmetric cyanosilylation of aldehydes
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A novel chiral (salen)AlIII complex was synthesized through the reaction of Et2AlCl and salen (R,R)-1 derived from (R,R)-11,12-diamino-9,10-dihydro-9,10-ethanoanthracene. This complex is an efficient catalyst for the asymmetric trimethylsilylcyanation of aldehydes in the presence of tributylphosphane oxide as an additive. The use of 1 mol-% of the complex led to the corresponding cyanohydrins in high yields (85-94%) with good-to-excellent enantioselectivities (42-92%ee). Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Zeng, Zebing,Zhao, Guofeng,Zhou, Zhenghong,Tang, Chuchi
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experimental part
p. 1615 - 1618
(2009/04/11)
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- A new strategy for designing non-C2-symmetric monometallic bifunctional catalysts and their application in enantioselective cyanation of aldehydes
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A monometallic bifunctional catalyst, in which only one imidazolyl moiety is directly attached at the 3-position of a binaphthol moiety, has been developed. The ligand (R)-1, which lacks C2-symmetry and flexible linkers, in combination with Ti(OiPr)4, has been demonstrated to promote the enantioselective cyanation of aldehydes with trimethylsilylcyanide (TMSCN), giving excellent enantioselectivities of up to 98 % ee and high yields of up to 99%. The use of this bifunctional catalytic system obviates the need for additives and is extremely simple as the reagents are added in one portion at the beginning of the reaction. The protocol has been found to tolerate a relatively wide range of aldehydes when 10 mol% of the (R)-1/Ti(OiPr) 4 complex is deployed in CH2Cl2 at -40°C, the conditions which proved most practical and effective. The asymmetric cyanations also proceeded with lower catalyst loadings (5 mol%, or even 2 mol%), still giving satisfactory enantiomeric excesses and yields. Interestingly, the use of freshly distilled TMSCN dried over CaH2 gave a low enantioselectivity and only a moderate yield of the adduct as compared with direct use of the commercial reagent. The results of 13C NMR spectroscopic studies implicate HCN as the actual reactive nucleophile.
- Yang, Fei,Wei, Siping,Chen, Chien-An,Xi, Peihua,Yang, Li,Lan, Jingbo,Gau, Han-Mou,You, Jingsong
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supporting information; experimental part
p. 2223 - 2231
(2009/04/06)
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- [Ru(phgly)2(binap)]/Li2CO3: A Highly Active, Robust, and Enantioselective Catalyst for the Cyanosilylation of Aldehydes
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The right combination: A series of aromatic, heteroaromatic, aliphatic, and α,β-unsaturated aldehydes can be converted into the desired silylated cyanohydrins by reaction with (CH3)3SiCN and a catalyst system consisting of the combination of a chiral ruthenium complex and Li2CO3 (see scheme). The reaction is highly enantioselective and affords the R products with up to 98% ee within 24 h at a substrate-tocatalyst ratio of 10000:1. (Chemical Equation Presented).
- Kurono, Nobuhito,Arai, Kenta,Uemura, Masato,Ohkuma, Takeshi
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supporting information; experimental part
p. 6643 - 6646
(2009/03/12)
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- Synthesis of the bifunctional BINOL ligands and their applications in the asymmetric additions to carbonyl compounds
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Efficient one-step syntheses of the bifunctional BINOL and H8BINOL ligands (S)-6 and (S)-8 have been developed from the reaction of BINOL and H8BINOL with morpholinomethanol, respectively. The X-ray analyses of these compounds have revealed their structural similarity and difference. The bifunctional H8BINOL (S)-8 is found to be highly enantioselective for the reaction of diphenylzinc with many aliphatic and aromatic aldehydes and especially is the most enantioselective catalyst for linear aliphatic aldehydes. Unlike other catalysts developed for the diphenylzinc addition which often require the addition of a significant amount of diethylzinc with cooling (or heating) the reaction mixture in order to achieve high enantioselectivity, using (S)-8 needs no additive and gives excellent results at room temperature. (S)-8 in combination with diethylzinc and Ti(OiPr)4 can catalyze the highly enantioselective phenylacetylene addition to aromatic aldehydes. It can also promote the phenylacetylene addition to acetophenone at room temperature though the enantioselectivity is not very high yet. Without using Ti(OiPr)4 and a Lewis base additive, (S)-8 in combination with diethylzinc can catalyze the reaction of methyl propiolate with an aldehyde to form the highly functional γ-hydroxy-α,β-acetylenic esters except that the enantioselectivity is low at this stage. The bifunctional BINOL ligand (S)-6 in combination with Me2AlCl is found to be a highly enantioselective catalyst for the addition of TMSCN to both aromatic and aliphatic aldehydes.
- Qin, Ying-Chuan,Liu, Lan,Sabat, Michal,Pu, Lin
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p. 9335 - 9348
(2007/10/03)
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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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- Enantioselective cyanosilylation of aldehydes catalysed by a diastereomeric mixture of atropisomeric thioureas
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New bifunctional atropisomeric thioureas 1 were synthesised and tested as both a mixture of diastereomers (aR/aS)-(R,R)-1 and as single diastereomers (aR)-(R,R)-1 and (aR)-(S,S)-1, in the organocatalysed, enantioselective, cyanosilylation of a range of al
- Steele, Rebecca M.,Monti, Chiara,Gennari, Cesare,Piarulli, Umberto,Andreoli, Federico,Vanthuyne, Nicolas,Roussel, Christian
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p. 999 - 1006
(2007/10/03)
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- Asymmetric cyanohydrin synthesis catalyzed by Al(salen)/triphenylphosphane oxide
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Various aldehydes undergo asymmetric trimethylsilylcyanation with (CH 3)3SiCN (TMSCN) in the presence of a chiral Al(salen) complex and Ph3PO as the catalyst. This is a double activation where Al(salen) plays the role of Lewis acd and POPh3 acts as a Lewis base. Various kind of aldehydes were subjected to the enantioselective addition of (CH3)3SiCN at temperatures between -40 °C and -50 °C. Hydrolysis of the adducts gave cyanohydrins with over 90 % yield and 80 % ee in most cases. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
- Kim, Sung Soo,Song, Dae Ho
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p. 1777 - 1780
(2007/10/03)
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- Highly enantioselective cyanosilylation of aldehydes catalyzed by novel β-amino alcohol-titanium complexes
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The β-amino alcohol 1b-Ti(Oi-Pr)4 complex has been shown to catalyze the enantioselective cyanosilylation of aldehydes efficiently. In the presence of 5 mol % of 1b-Ti(Oi-Pr)4 complex catalyst, the aromatic, conjugated, heteroaromatic, and aliphatic aldehydes were converted to their corresponding trimethylsilyl ethers of cyanohydrins in 90-99% yields with up to 94% ee under mild conditions.
- Li, Yan,He, Bin,Qin, Bo,Feng, Xiaoming,Zhang, Guolin
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p. 7910 - 7913
(2007/10/03)
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- Enantioselective addition of trimethylsilyl cyanide to aldehydes catalysed by bifunctional BINOLAM-AlCl versus monofunctional BINOL-AlCl complexes
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A highly enantioselective cyanation of aldehydes takes place by using a bifunctional catalyst derived from 3,3′-bis(diethylaminomethyl) substituted binaphthol (BINOLAM) and dimethylaluminium chloride. The addition is of wide scope and runs best in toluene at temperatures ranging from -20 to -40°C, in the presence of 4 A? MS and triphenylphosphine oxide as additives. The (R)- or (S)-cyanohydrins result when using (S)- or (R)-BINOLAM-AlCl complexes, respectively. The valuable ligand can be recovered by simple extractive work-up and recycled without loss of efficiency (both in terms of chemical and stereochemical yields). This methodology is applied to the Shibasaki synthesis of epothilone A. All the evidence available for the BINOLAM-AlCl enantioselective addition of TMSCN to aldehydes call for the intervention of a hydrocyanation reaction, addition of a catalytic amount of hydrogen cyanide, generated in situ, to an aldehyde, followed by O-silylation. In order to determine the role of the basic amino groups of BINOLAM, comparative studies are carried out with the monofunctional 1,1′-binaphthol-derived complex BINOL-AlCl. Graphical Abstract.
- Casas, Jesús,Nájera, Carmen,Sansano, José M.,Saá, José M.
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p. 10487 - 10496
(2007/10/03)
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- Evaluation of guanabana (Annona muricata) seed meal as a source of (S)-oxynitrilase
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Guanabana seed meal is a source of (S)-oxynitrilase which biocatalyzes the enantioselective addition of HCN to aromatic, heteroaromatic and α,β-unsaturated aldehydes to produce cyanohydrins.
- Solis, Aida,Luna, Hector,Perez, Herminia I.,Manjarrez, Norberto
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p. 2351 - 2353
(2007/10/03)
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- BINOLAM, a recoverable chiral ligand for bifunctional enantioselective catalysis: The asymmetric synthesis of cyanohydrins
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(Matrix presented) A new bifunctional catalytic system based on a monometallic aluminum complex is used for the efficient enantioselective cyanation of aldehydes. The ligand (S)- or (R)-2,2′-bis(diethylaminomethyl)-substituted binaphthol (BINOLAM) used is
- Casas, Jesus,Najera, Carmen,Sansano, Jose M.,Saa, Jose M.
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p. 2589 - 2592
(2007/10/03)
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- Highly enantioselective cyanosilylation of aldehydes catalyzed by a Lewis acid-Lewis base bifunctional catalyst
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A new bifunctional asymmetric catalyst containing a Lewis acid and a Lewis base (1) was developed and applied to the catalytic asymmetric cyanosilylation of aldehydes. The products were obtained generally with excellent enantiomeric excess. The experiment
- Hamashima, Yoshitaka,Sawada, Daisuke,Nogami, Hiroyuki,Kanai, Motomu,Shibasaki, Masakatsu
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p. 805 - 814
(2007/10/03)
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- Zr(OBut)4 as an effective promoter for the Meerwein-Ponndorf-Verley alkynylation and cyanation of aldehydes: Development of new asymmetric cyanohydrin synthesis
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Zr(OBut)4 can serve as an effective promoter for the Meerwein-Ponndorf-Verley alkynylation of aldehydes and also facilitate MPV type cyanide transfer to aldehyde carbonyls with commercially available acetone cyanohydrin under mild conditions. Based on this finding, a new procedure for asymmetric cyanohydrin synthesis has been developed employing (4R,5R)-2,2-dimethyl-α,α,α′,α′-tetraph enyl-1,3-dioxolane-4,5-dimethanol (TADDOL, 6) as a chiral ligand. For instance, sequential treatment of CH2Cl2 solution of 6 (1 equiv.) with Zr(OBut)4 (1 equiv.) and acetone cyanohydrin (2 equiv.) at room temperature for 1 h, and subsequent reaction with 3-phenylpropanal at -40°C for 7.5 h resulted in formation of the corresponding cyanohydrin 5g [R=Ph(CH2)2] in 63% isolated yield with 85% ee. The scope and limitations of this method have been clarified with various aldehydes as substrates.
- Ooi, Takashi,Miura, Tomoya,Takaya, Keisuke,Ichikawa, Hayato,Maruoka, Keiji
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p. 867 - 873
(2007/10/03)
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- Chiral zirconium alkoxides-mediated asymmetric Meerwein-Ponndorf-Verley cyanation of aldehydes
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Chiral zirconium alkoxides prepared in situ from Zr(OBu(t))4, TADDOL and acetone cyanohydrin in CH2Cl2 effect the enantioselective Meerwein-Ponndorf-Verley cyanation of alde-hydes, giving optically active cyanohydrins. The
- Ooi,Takaya,Miura,Ichikawa,Maruoka
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p. 1133 - 1134
(2007/10/03)
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- Catalytic, asymmetric cyanohydrin synthesis mediated by lanthanide(III) chloride pybox complexes
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Complexes formed between lanthanide trichlorides and 2,6- bis(substituted-2-oxazolin-2-yl)pyridine (pybox) ligands are effective catalysts for the enantioselective addition of trimethylsilylcyanide (TMSCN) to a range of aldehydes.
- Aspinall, Helen C.,Greeves, Nicholas,Smith, Peter M.
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p. 1763 - 1766
(2007/10/03)
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- Enzymatic Synthesis of (R)-Cyanohydrins by Three (R)-Oxynitrilase Sources in Micro-aqueous Organic Medium
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The enantioselective synthesis of optically active (R)-cyanohydrins generated from several aromatic, heteroaromatic and aliphatic aldehydes and methyl ketones was carried out using almond, peach or loquat meal as (R)-oxynitrilase sources in diisopropylether under micro-aqueous conditions The micro-aqueous reaction system, which is superior to the conventionally used water-organic biphase reaction system, performed well over the temperature range of 4 deg C to 30 deg C.
- Lin, Guoqiang,Han, Shiqing,Li, Zuyi
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p. 3531 - 3540
(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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- Examination and Enhancement of Enantioselective Autoinduction in Cyanohydrin Formation by Cyclo[ (R)-His- (R)-Phe]
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The cyclic dipeptide cyclo[(R)-His-(R)-Phe] (1) has been known since 1981 to catalyze the enantioselective formation of cyanohydrins from aldehydes and HCN. Although 1 has proved to be very effective in the production of optically active cyanohydrins, the precise structure of its catalytically active form remains unresolved. The reaction of 3-phenoxybenzaldehyde and HCN in the presence of 1 has also been shown to exhibit enantioselective autocatalysis: the product (S)-3-phenoxymandelonitrile reacts with 1 to form a new, more enantioselective catalytic species. It is now demonstrated that this autocatalytic phenomenon is general and that, furthermore, it can be used to improve the enantioselectivity of cyanohydrin formation for several problematic substrates. Upon addition of a small (8 mol %) quantity of (S)-mandelonitrile or (S)-3-phenoxymandelonitrile to these reactions, the enantioselectivity of cyanohydrin formation was improved by as much as 20% ee. This effect has been ascribed to the formation of a complex between the added (S)-cyanohydrin and 1 that exhibits superior enantioselectivity to 1, either alone or complexed to the cyanohydrins of problematic substrates. A mathematical model has been developed, on the basis of a two-state equilibrium between 1 and a complex of 1 and cyanohydrin and used to explain the enantioselective autoinduction phenomenon in terms of five parameters: rate constants for the production of (R)- and (S)-cyanohydrin by both 1 and its cyanohydrin complex and an association constant for the formation of a cyanohydrin complex by 1. Two versions of this model, based on monomeric and dimeric 1, have been evaluated in light of the available data. Examination of the results reveals that the complexes of 1 and many of the cyanohydrins studied are highly enantioselective catalysts but that the complexes of 1 and cyanohydrins are only weakly associated; moreover, the complexation of 1 with most cyanohydrins leaves the rate of cyanohydrin formation unchanged, though both autocatalysis and enantioselective poisoning have been observed as well.
- Kogut, Eugene F.,Thoen, Jason C.,Lipton, Mark A.
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p. 4604 - 4610
(2007/10/03)
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- Stereoselective synthesis of thienyl and furyl analogues of ephedrine
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The stereoselective syntheses of thienyl and furyl analogues of ephedrine starting from (R)- and (S)-cyanohydrins, respectively, are described. Addition of methyl Grignard to the O-trimethylsilyl protected optically active cyanohydrins (R)- and (S)-3 and hydrogenation of the resulting imino intermediates gives the erythro-2-amino alcohols 4 with high diastereoselectivity. Their reductive methylation leads to the enantiomerically pure thiophene analogues (1S,2S)- and (1R,2R)-6a, (1R,2S)- and (1S,2R)-6b as well as to the furan analogues (1S,2S)-6c and (1R,2S)-6d of ephedrine, The biological activity of the new compounds is under investigation.
- Effenberger, Franz,Eichhorn, Joachim
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p. 469 - 476
(2007/10/03)
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- Preparation of optically active cyanohydrins using the (S)-hydroxynitrile lyase from Hevea brasiliensis
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Several aliphatic, aromatic and heteroaromatic aldehydes have been converted into the chiral cyanohydrins using the (S) hydroxynitrile lyase from Hevea brasiliensis. The corresponding cyanohydrins were obtained in moderate to good yield and high enantiomeric excess with the exeption of phenyloxyacetaldehyde, benzyloxyacetaldehyde and the pyrrole-, pyridine- and indolealdehydes investigated. In contrast to previously reported results, cinnamaldehyde could be converted into (S)-(-)-2-hydroxy-4-phenyl-(E)-but-3- enenitrile with good selectivity by means of optimized reaction conditions.
- Schmidt, Michael,Herve, Stephanie,Klempier, Norbert,Griengl, Herfried
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p. 7833 - 7840
(2007/10/03)
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- One-Pot Synthesis of Optically Active Cyanohydrin Acetates from Aldehydes via Quinidine-Catalyzed Transhydrocyanation Coupled with Lipase-Catalyzed Kinetic Resolution in Organic Solvent
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A novel one-pot synthetic method was developed for the preparation of optically active cyanohydrin acetates.Racemic cyanohydrins were generated from aldehydes and acetone cyanohydrin by quinidine-catalyzed transhydrocyanation, and the resulting cyanohydrins 2a-j were then acetylated by lipase in a stereoselective manner using isopropenyl acetate as an acylating reagent.A variety of aldehydes 1a-j were successfully transformed into the corresponding cyanohydrin acetates 3a-j having 47-95percent e.e. without isolating the unstable cyanohydrins 2.Moreover, the reversible nature of base-catalyzed transhydrocyanation allows for in situ racemization of the unreacted cyanohydrins and concurrent kinetic resolution by lipase enabled the preparation of (S)-3b-d with 40-82percent e.e. in more than 50percent yield.Polymer-supported cinchona alkaloid was also used as a catalyst for this one-pot reaction and showed the comparable chemical and optical yield to that for the soluble monomeric alkaloid.The insoluble polymer and lipase were recovered by filtration and found to have almost the same catalytic activity even after four times of reuse.
- Inagaki, Minoru,Hatanaka, Akihiko,Mimura, Mitsuo,Hiratake, Jun,Nishioka, Takaaki,Oda, Jun'ichi
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p. 111 - 120
(2007/10/02)
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- Peptide-titanium complex as catalyst for asymmetric addition of hydrogen cyanide to aldehyde
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The complex of titanium ethoxide and an acyclic dipeptide ester whose terminal amino group is modified to a salicylal-type Schiff base catalyzes the asymmetric addition of hydrogen cyanide to aldehydes with high enantioselectivity. In the reaction of benzaldehyde and hydrogen cyanide, (R)-mandelonitrile is obtained with an enantiomeric excess of 90% when N-((2-hydroxy-1-naphthyl)methylene)-(S)-valyl-(S)-tryptophan methyl ester is employed. In place of the dipeptide, the amide derivatives of an amino acid modified by substituted salicylaldehyde, such as N-(3,5-dibromosalicylidene)-(S)-valine piperidide, exhibit an entirely opposite stereoselectivity to yield S-cyanohydrins with optical purities up to 97% ee. This novel peptide-titanium complex, therefore, enables us to afford optically active cyanohydrins of both absolute configurations by using natural S-amino acids as chiral auxiliaries.
- Nitta, Hideaki,Yu, Donghai,Kudo, Masanobu,Mori, Atsunori,Inoue, Shohei
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p. 7969 - 7975
(2007/10/02)
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- A NEW ACCESS TO CHIRAL 2-FURYLCARBINOLS BY ENANTIOSELECTIVE HYDROLYSIS WITH PENICILLIN ACYLASE
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The phenylacetic acid esters of 2-furylcarbinols were enantioselectively hydrolyzed with the aid of penicillin acylase.
- Waldmann, Herbert
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p. 3057 - 3058
(2007/10/02)
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- Asymmetric Hydrocyanation of a Range of Aromatic and Aliphatic Aldehydes
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A range of aryl, alkyl and heterocyclic aldehydes have been treated with hydrogen cyanide in the presence of the 'Inoue' catalyst, (R,R)- or (S,S)-cyclo.Most aryl aldehydes with electron-donating substituents in the m-or p-positions give high enantiomeric excess (e.e) values (>=80percent) but aryl aldehydes with strong electron-withdrawing substituents gave moderate e.e. values (=50percent).These moderate values are believed to be due to partial racemization of the product cyanohydrins in the presence of the mildly basic catalyst.In contrast to the reactions of aryl aldehydes, reactions of alkyl aldehydes and of ketones gave low e.e. values (=30percent) and an explanation is proposed.
- Matthews, Barry R.,Jackson, W. Roy,Jayatilake, Gamini S.,Wilshire, Colin,Jacobs, Howard A.
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p. 1697 - 1710
(2007/10/02)
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