- The Oxidation of Benzaldehyde to Benzoic Acid Catalysed by Cyclo-, and its Implications for the Catalytic Assymmetric Addition of HCN to Aldehydes
-
Key Words: cyclo-; Benzaldehyde; Oxidation; Asymmetric Hydrocyanation; Mechanism The cyclic dipeptide cyclo- is found to catalyse the oxidation of benzaldehyde to benzoic acid.A mechanism is proposed both for this reactio
- Hogg, David J.P.,North, Michael,Stokoe, Robert B.,Teasdale, William G.
-
-
Read Online
- Salen-ligands based on a planar-chiral hydroxyferrocene moiety: Synthesis, coordination chemistry and use in asymmetric silylcyanation
-
Condensation of the O-protected hydroxyferrocene carbaldehyde (Sp)-1 with suitable diamines, followed by liberation of the hydroxyferrocene moiety leads to a new type of ferrocene-based salen ligands (3). While the use of ethylenediamine in the
- Niemeyer, Jochen,Cloppenburg, Jeannine,Fr?hlich, Roland,Kehr, Gerald,Erker, Gerhard
-
-
Read Online
- Asymmetric Cyanohydrin Synthesis catalysed by a Synthetic Cyclic Dipeptide
-
Asymmetric addition of hydrogen cyanide to benzaldehyde catalysed by cyclo(L-phenylalanyl-L-histidine) gave the highest optical yield ever obtained.
- Oku, Jun-ichi,Inoue, Shohei
-
-
Read Online
- Asymmetric synthesis XXVII: Asymmetric catalytic trimethylsilylcyanation of aldehydes by novel Ti-chiral Schiff base complexes
-
Enantioselective catalytic trimethylsilylcyanations of aldehydes with 48% to 92% e.e. have been studied using the novel Ti-chiral Schiff base complexes. We have found that the catalyst led to high enantioselectivity when the molar ratio of the Schiff base
- Jiang,Zhou,Hu,Li,Mi
-
-
Read Online
- Trimethylsilylcyanation of aromatic aldehydes catalyzed by Pybox-AlCl3 complex
-
A series of aromatic and heterocyclic cyanohydrins and their O-silyl ethers have been synthesized by trimethylsilylcyanation of aldehydes using a catalyst generated in situ from (S,S)-2,6-bis(4'-isopropyloxazolin-2'-yl)pyridine (Pybox) with AlCl3/su
- Iovel, Irina,Popelis, Yuris,Fleisher, Mendel,Lukevics, Edmunds
-
-
Read Online
- Catalytic Promiscuity of Ancestral Esterases and Hydroxynitrile Lyases
-
Catalytic promiscuity is a useful, but accidental, enzyme property, so finding catalytically promiscuous enzymes in nature is inefficient. Some ancestral enzymes were branch points in the evolution of new enzymes and are hypothesized to have been promiscuous. To test the hypothesis that ancestral enzymes were more promiscuous than their modern descendants, we reconstructed ancestral enzymes at four branch points in the divergence hydroxynitrile lyases (HNL's) from esterases ~100 million years ago. Both enzyme types are α/β-hydrolase-fold enzymes and have the same catalytic triad, but differ in reaction type and mechanism. Esterases catalyze hydrolysis via an acyl enzyme intermediate, while lyases catalyze an elimination without an intermediate. Screening ancestral enzymes and their modern descendants with six esterase substrates and six lyase substrates found higher catalytic promiscuity among the ancestral enzymes (P 0.01). Ancestral esterases were more likely to catalyze a lyase reaction than modern esterases, and the ancestral HNL was more likely to catalyze ester hydrolysis than modern HNL's. One ancestral enzyme (HNL1) along the path from esterase to hydroxynitrile lyases was especially promiscuous and catalyzed both hydrolysis and lyase reactions with many substrates. A broader screen tested mechanistically related reactions that were not selected for by evolution: decarboxylation, Michael addition, γ-lactam hydrolysis and 1,5-diketone hydrolysis. The ancestral enzymes were more promiscuous than their modern descendants (P = 0.04). Thus, these reconstructed ancestral enzymes are catalytically promiscuous, but HNL1 is especially so.
- Devamani, Titu,Rauwerdink, Alissa M.,Lunzer, Mark,Jones, Bryan J.,Mooney, Joanna L.,Tan, Maxilmilien Alaric O.,Zhang, Zhi-Jun,Xu, Jian-He,Dean, Antony M.,Kazlauskas, Romas J.
-
-
Read Online
- Chiral sulfoxide ligands in catalytic asymmetric cyanohydrin synthesis
-
A novel chiral sulfoxide-containing ligand for the catalytic addition of trimethylsilylcyanide to aldehydes is reported. The sulfoxide moiety was found to be vital for reactivity.
- Rowlands, Gareth J.
-
-
Read Online
- Asymmetric synthesis of an (R)-cyanohydrin using enzymes entrapped in lens-shaped gels.
-
[structure: see text] A novel synthesis of (R)-cyanohydrins is described which is based on the use of cross-linked and subsequently poly(vinyl alcohol)-entrapped (R)-oxynitrilases. These immobilized lens-shaped biocatalysts have a well-defined macroscopic
- Groeger,Capan,Barthuber,Vorlop
-
-
Read Online
- One-pot chemoenzymatic synthesis of protected cyanohydrins
-
In a chemoenzymatic one-pot reaction of ethyl cyanoformate with benzaldehyde catalyzed by the hydroxynitrile lyase from Prunus amygdalus ethoxycarbonylated (R)-mandelonitrile is formed in a highly enatioselective manner. The reaction was performed both in
- Purkarthofer, Thomas,Skranc, Wolfgang,Weber, Hansj?rg,Griengl, Herfried,Wubbolts, Marcel,Scholz, Gerald,P?chlauer, Peter
-
-
Read Online
- Hydroxynitrile Lyase of Wild Apricot (Prunus armeniaca L.): Purification, Characterization and Application in Synthesis of Enantiopure Mandelonitrile
-
Abstract: Hydroxynitrile lyases (HNLs) are increasingly finding application in synthesis of enantiomerically pure cyanohydrins. Cyanohydrins are important intermediates in the production of pharmaceuticals and agrochemicals. In the present studies seeds of wild apricot (Prunus armeniaca L.) have emerged as potential source of hydroxynitrile lyase. The HNL of wild apricot (ParsHNL) was purified 8.1 fold and 18.2?% yield with a specific activity of 141 units?mg?1 protein. The SDS-PAGE of the enzyme revealed that it consists of subunits of 40 and 37?kDa. However, the molecular weight of holoenzyme was assessed to be 360?kDa. The enzyme showed maximum activity in 0.1?M sodium-citrate buffer having pH 4.75 at 25?°C. Thermostability studies revealed that this HNL showed activity up to 70?°C temperature and quite stable up to 50?°C. Activation energy of ParsHNL was calculated to be 37.83?kJ?mol?1. This enzyme has Km of 3.76?mM, Vmax of 188.4?μmol?mg?1 min?1 and kcat of 1130.4?s?1 using mandelonitrile as substrate while for reverse reaction using benzaldehyde as substrate it showed Km of 16.1?mM, Vmax of 7.21?μmol?mg?1 min?1 and kcat of 43.3?s?1. Synthesis of mandelonitrile was carried out using ParsHNL and finally 8.88?mmole (1.184?g) of mandelonitrile was recovered which corresponded to 89?% molar conversion with 96?% ee for R-mandelonitrile. The yield of mandelonitrile was 411?μmol?mg?1h?1. These results indicated that ParsHNL has very high potential for synthesis of cyanohydrins and can be used for the production of enantiopure cyanohydrins. Graphical Abstract: [Figure not available: see fulltext.]
- Asif, Mohammad,Bhalla, Tek Chand
-
-
Read Online
- Toxicity and Toxicokinetics of Amygdalin in Maesil (Prunus mume) Syrup: Protective Effect of Maesil against Amygdalin Toxicity
-
Maesil (Prunus mume, green plum)-based products have been widely used in Asian cooking, which may contain amygdalin enzymatically converted to hydrogen cyanide after oral ingestion. In this study, the toxicity of Maesil syrups matured with and without Mae
- Go, Mi-Ran,Kim, Hyeon-Jin,Yu, Jin,Choi, Soo-Jin
-
-
Read Online
- Sol-Gel Glass with Enantioselective Catalytic Activity
-
Cyclo entrapped in a silicon based sol-gel glass matrix induces catalytic hydrocyanation of benzaldehyde to (R)-mandelonitrile with e.e. >= 94percent.
- Shvo, Youval,Becker, Yigal,Gal, Meir
-
-
Read Online
- Lipase-catalyzed kinetic resolution of (±)-mandelonitrile under conventional condition and microwave irradiation
-
The kinetic resolution of (±)-mandelonitrile was carried out using lipase from Candida antarctica under conventional condition (orbital shaker) and microwave irradiation in toluene, producing the (S)-mandelonitrile acetate with high selectivity (up to > 98percent ee, enantiomeric excess). The unreacted (R)-mandelonitrile under microwave irradiation and conventional condition was partially converted into benzaldehyde by spontaneous chemical equilibrium. The (S)-mandelonitrile acetate under microwave irradiation was produced with 92percent ee and 35percent yield for 8 h of reaction. Conventional transesterification of (±)-mandelonitrile in an orbital shaker produced unreacted (R)-mandelonitrile (51percent ee) and (S)-mandelonitrile acetate (98percent ee) in accordance with Kazlauskas rule for 184 h of reaction.
- Ribeiro, Sandra S.,De Oliveira, Julieta R.,Porto, Andre? L. M.
-
-
Read Online
- Straightforward enzymatic process based on HNL CLEA-catalysis towards cyanohydrin derivatives
-
An efficient enzymatic process based on HNL-CLEA catalysis in buffer-saturated organic media was developed to limit the amount of overall waste generated and the number of safety issues incurred by handling HCN-containing waste. Starting from benzaldehyde as a model substrate, (R)- and (S)-mandelonitrile can be obtained under these reaction conditions without an extraction step being required. The crude cyanohydrin intermediate was sufficiently pure to be used as starting material in a second step towards a range of derivatives.
- Cabirol, Fabien L.,Lim, Angela E. C.,Hanefeld, Ulf,Sheldon, Roger A.
-
-
Read Online
- Activity and enantioselectivity of the hydroxynitrile lyase MeHNL in dry organic solvents
-
Water concentration affects both the enantioselectivity and activity of enzymes in dry organic media. Its influence has been investigated using the hydrocyanation of benzaldehyde catalyzed by hydroxynitrile lyase cross-linked enzyme aggregate (A/eHNL-CLEA) as a model reaction. The enzyme displayed higher enantioselectivity at higher water concentration, thus suggesting a positive effect of enzyme flexibility on selectivity. The activity increased on reducing the solvent water content, but drastic dehydration of the enzyme resulted in a reversible loss of activity.
- Paravidino, Monica,Sorgedrager, Menno J.,Orru, Romano V. A.,Hanefeld, Ulf
-
-
Read Online
- (S)-3,3-Dimethyl-1,2,4-butanetriol as Ligand for Titanium Catalysed Asymmetric Silylcyanation
-
Trimethylsilylcyanation of benzaldehyde was effected in up to 76percent e.e. using a catalyst prepared from the triol obtained by reduction of D-Pantolactone and titanium isopropoxide.
- Callant, Dominique,Stanssens, Dirk,Vries, Johannes G. de
-
-
Read Online
- Comprehensive Step-by-Step Engineering of an (R)-Hydroxynitrile Lyase for Large-Scale Asymmetric Synthesis
-
A custom-made enzyme: The gene and protein sequence of a new (R)-hydroxynitrile lyase from Prunus amygdalus was cloned and engineered for recombinant production on a large scale. The enzyme is stable and active at low pH values. A rationally designed acti
- Glieder, Anton,Weis, Roland,Skranc, Wolfgang,Poechlauer, Peter,Dreveny, Ingrid,Majer, Sandra,Wubbolts, Marcel,Schwab, Helmut,Gruber, Karl
-
-
Read Online
- Proline adducts of metallo-organic, sextuply-stranded lanterns as homogeneous catalysts for asymmetric catalysis
-
Two homochiral metal-organic, sextuply-stranded, lantern-like complexes, Ce-L-Pro1 and Ce-D-Pro1, were synthesized via self-assembly by incorporating a L or D-pyrrolidine moiety within the respective ligands. The Ce-Pro1 complexes are comprised of chiral pyrrolidine-containing ligands and have lantern-like cavities. They function as asymmetric catalysts that promote cyanosilylation reactions with good conversions and enantioselectivity.
- Zhu, Wenting,Wu, Xiao,He, Cheng,Duan, Chunying
-
-
Read Online
- Immobilized Baliospermum montanum hydroxynitrile lyase catalyzed synthesis of chiral cyanohydrins
-
Hydroxynitrile lyase (HNL) catalyzed enantioselective C–C bond formation is an efficient approach to synthesize chiral cyanohydrins which are important building blocks in the synthesis of a number of fine chemicals, agrochemicals and pharmaceuticals. Immobilization of HNL is known to provide robustness, reusability and in some cases also enhances activity and selectivity. We optimized the preparation of immobilization of Baliospermium montanum HNL (BmHNL) by cross linking enzyme aggregate (CLEA) method and characterized it by SEM. Optimization of biocatalytic parameters was performed to obtain highest % conversion and ee of (S)-mandelonitrile from benzaldehyde using CLEA-BmHNL. The optimized reaction parameters were: 20 min of reaction time, 7 U of CLEA-BmHNL, 1.2 mM substrate, and 300 mM citrate buffer pH 4.2, that synthesized (S)-mandelonitrile in ~99% ee and ~60% conversion. Addition of organic solvent in CLEA-BmHNL biocatalysis did not improve in % ee or conversion of product unlike other CLEA-HNLs. CLEA-BmHNL could be successfully reused for eight consecutive cycles without loss of conversion or product formation and five cycles with a little loss in enantioselectivity. Eleven different chiral cyanohydrins were synthesized under optimal biocatalytic conditions in up to 99% ee and 59% conversion, however the % conversion and ee varied for different products. CLEA-BmHNL has improved the enantioselectivity of (S)-mandelonitrile synthesis compared to the use of purified BmHNL. Nine aldehydes not tested earlier with BmHNL were converted into their corresponding (S)-cyanohydrins for the first time using CLEA-BmHNL. Among the eleven (S)-cyanohydrins syntheses reported here, eight of them have not been synthesized by any CLEA-HNL. Overall, this study showed preparation, characterization of a stable, robust and recyclable biocatalyst i.e. CLEA-BmHNL and its biocatalytic application in the synthesis of different (S)-aromatic cyanohydrins.
- Jangir, Nisha,Padhi, Santosh Kumar
-
-
Read Online
- Partial purification and immobilization of a new (R)-hydroxynitrile lyase from seeds of Prunus pseudoarmeniaca
-
Hydroxynitrile lyase (HNL) from seeds of Prunus pseudoarmeniaca was partially purified by (NH4)2SO4 fractionation and covalently immobilized onto Eupergit C and Eupergit C 250 L. The percentages of bound protein per gram o
- Tuekel, S. Seyhan,Yildirim, Deniz,Alagoez, Dilek,Alptekin, Oezlem,Yuecebilgi, Guezide,Bilgin, Ramazan
-
-
Read Online
- Enantioselective trimethylsilylcyanation of aromatic aldehydes catalyzed by titanium alkoxide-chiral o-hydroxyarylphosphine oxides complexes
-
A series of new chiral titanium alkoxide-o-hydroxyarylphosphine oxides complexes has been used as catalysts in the asymmetric trimethylsilylcyanation of aromatic aldehydes. The corresponding cyanohydrins have been obtained in high chemical yields with good to excellent enantiomeric excesses up to 98%. The influence of the structural features of the catalysts on the enantioselectivity has been investigated.
- Brunel, Jean-Michel,Legrand, Olivier,Buono, Gerard
-
-
Read Online
- Temperature-triggered switchable helix-helix inversion of poly(phenylacetylene) bearing L-valine ethyl ester pendants and its chiral recognition ability
-
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
-
-
Read Online
- An enantioselective synthesis of the Williams glycine template
-
The Williams glycine template for amino acid synthesis, benzyl (2R,3S)-6-oxo-2,3-diphenyl-4-morpholinecarboxylate (1), was prepared in enantiomerically pure form in six steps from benzaldehyde in 48% overall yield. The initial chirality of the molecule wa
- Van Den Nieuwendijk,Warmerdam,Brussee,Van Der Gen
-
-
Read Online
- Synthesis of enantiomerically pure (S)-mandelic acid using an oxynitrilase-nitrilase bienzymatic cascade: A nitrilase surprisingly shows nitrile hydratase activity
-
Benzaldehyde was converted into enantiomerically pure (S)-mandelic acid by sequential HCN addition and hydrolysis in the presence of a cross-linked enzyme aggregate composed of the (S)-selective oxynitrilase from Manihot esculenta and the non-selective recombinant nitrilase from Pseudomonas fluorescens EBC 191. Surprisingly, (S)-mandelic amide was formed in large amounts. It was shown, in separate experiments, that the nitrilase hydrolyses (S)-mandelonitrile into an approx. equimolar mixture of acid and amide, whereas with the (R)-enantiomer only 10% of amide was formed.
- Mateo, Cesar,Chmura, Andrzej,Rustler, Sven,Van Rantwijk, Fred,Stolz, Andreas,Sheldon, Roger A.
-
-
Read Online
- Sorghum bicolor shoots in the synthesis of (S)-mandelonitrile
-
An inexpensive method for the preparation of (S)-mandelonitrile from benzaldehyde and HCN in diisopropyl ether with the chemical yield and enantiomeric excess of ca. 90% is described. In this method, (S)-oxynitrilase in etiolated shoots of Sorghum bicolor
- Kiljunen,Kanerva
-
-
Read Online
- Probing batch and continuous flow reactions in organic solvents:Granulicella tundricolahydroxynitrile lyase (GtHNL)
-
Granulicella tundricolahydroxynitrile lyase (GtHNL) is a manganese dependent cupin which catalyses the enantioselective synthesis of (R)-cyanohydrins. TheGtHNL triple variant A40H/V42T/Q110H, previously reported to exhibit a high activity and stability, w
- Coloma, José,Guiavarc'h, Yann,Hagedoorn, Peter-Leon,Hanefeld, Ulf
-
-
Read Online
- Asymmetric synthesis XXII: Asymmetric catalytic trimethylsilylcyanation of benzaldehyde by novel Ti(IV)-chiral Schiff base complexes
-
Benzaldehyde has been trimethylsilylcyanated with a catalyst prepared in situ from titanium tetraisopropoxide and a novel chiral Schiff base. Both (R) and (S) cyanohydrins are obtained in moderate e.e. values.
- Jiang,Zhou,Hu,Wu,Mi
-
-
Read Online
- R-hydroxynitrile lyase from the cyanogenic millipede, Chamberlinius hualienensis—A new entry to the carrier protein family Lipocalines
-
Hydroxynitrile lyases (HNLs) catalyze the cleavage of cyanohydrin into cyanide and the corresponding aldehyde or ketone. Moreover, they catalyze the synthesis of cyanohydrin in the reverse reaction, utilized in industry for preparation of enantiomeric pure pharmaceutical ingredients and fine chemicals. We discovered a new HNL from the cyanogenic millipede, Chamberlinius hualienensis. The enzyme displays several features including a new primary structure, high stability, and the highest specific activity in (R)-mandelonitrile ((R)-MAN) synthesis (7420 U·mg?1) among the reported HNLs. In this study, we elucidated the crystal structure and reaction mechanism of natural ChuaHNL in ligand-free form and its complexes with acetate, cyanide ion, and inhibitors (thiocyanate or iodoacetate) at 1.6, 1.5, 2.1, 1.55, and 1.55?? resolutions, respectively. The structure of ChuaHNL revealed that it belongs to the lipocalin superfamily, despite low amino acid sequence identity. The docking model of (R)-MAN with ChuaHNL suggested that the hydroxyl group forms hydrogen bonds with R38 and K117, and the nitrile group forms hydrogen bonds with R38 and Y103. The mutational analysis showed the importance of these residues in the enzymatic reaction. From these results, we propose that K117 acts as a base to abstract a proton from the hydroxyl group of cyanohydrins and R38 acts as an acid to donate a proton to the cyanide ion during the cleavage reaction of cyanohydrins. The reverse mechanism would occur during the cyanohydrin synthesis. (Photo: Dr. Yuko Ishida). Databases: Structural data are available in PDB database under the accession numbers 6JHC, 6KFA, 6KFB, 6KFC, and 6KFD.
- Motojima, Fumihiro,Izumi, Atsushi,Nuylert, Aem,Zhai, Zhenyu,Dadashipour, Mohammad,Shichida, Sayaka,Yamaguchi, Takuya,Nakano, Shogo,Asano, Yasuhisa
-
-
Read Online
- Enantiopure Synthesis of (R)-Mandelonitrile Using Hydroxynitrile Lyase of Wild Apricot (Prunus armeniaca L.) [ParsHNL] in Aqueous/Organic Biphasic System
-
Abstract: Hydroxynitrile lyases (HNLs) are increasingly finding application in the synthesis of enantiomerically pure cyanohydrins which are important intermediates in the production of pharmaceuticals and agrochemicals. Synthesis of enantiopure mandelonitrile was carried out using HNL of wild apricot (Prunus armeniaca L.) [ParsHNL] in aqueous/organic biphasic system. The optimum pH and temperature of the reaction were 4.0 and 15 °C respectively, which are important parameters to suppress the non-enzymatic catalysis. ParsHNL catalyses synthesis of (R)-mandelonitrile in methyl-tbutyl ether (MTBE)/citrate buffer biphasic system with >99% ee. Synthesis of mandelonitrile was carried out in batch reaction at 40?ml scale and finally 2.7 mmoles of (R)-mandelonitrile was recovered which corresponded to 90% molar conversion in 46?h reaction. In fed batch reaction 6.37 mmoles of (R)-mandelonitrile could be produced which corresponds to 91% molar conversion in 46?h. In both reactions, enzyme produces (R)-mandelonitrile with > 99% ee which showed enhanced selectivity as compared to aqueous reaction (96% ee) by ParsHNL. The results showed potential of ParsHNL to synthesize (R)-mandelonitrile in both, batch reaction and fed-batch reaction and can be effectively used in the synthesis of (R)-mandelonitrile. Graphical Abstract: [Figure not available: see fulltext.].
- Asif, Mohammad,Bhalla, Tek Chand
-
-
Read Online
- A study on increasing enzymatic stability and activity of Baliospermum montanum hydroxynitrile lyase in biocatalysis
-
HNL catalysis is usually carried out in a biphasic solvent and at low pH to suppress the non-enzymatic synthesis of racemic cyanohydrins. However, enzyme stability under these conditions remain a challenge. We have investigated the effect of different biocatalytic parameters, i.e., pH, temperature, buffer concentrations, presence of stabilizers, organic solvents, and chemical additives on the stability of Baliospermum montanum hydroxynitrile lyase (BmHNL). Unexpectedly, glycerol (50 mg/mL) added BmHNL biocatalysis had produced >99% of (S)-mandelonitrile from benzaldehyde, while without glycerol it is 54% ee. Similarly, BmHNL had converted 3-phenoxy benzaldehyde and 3,5-dimethoxy benzaldehyde, to their corresponding cyanohydrins in the presence of glycerol. Among the different stabilizers added to BmHNL at low pH, 400 mg/mL of sucrose had increased enzyme's half-life more than fivefold. BmHNL's stability study showed half-lives of 554, 686, and 690 h at its optimum pH 5.5, temperature 20 °C, buffer concentration, i.e., 100 mM citrate-phosphate pH 5.5. Addition of benzaldehyde as inhibitor, chemical additives, and the presence of organic solvents have decreased both the stability and activity of BmHNL, compared to their absence. Secondary structural study by CD-spectrophotometer showed that BmHNL's structure is least affected in the presence of different organic solvents and temperatures.
- Jangir, Nisha,Preeti,Padhi, Santosh Kumar
-
-
Read Online
- Effect of Glycosylation on the Biocatalytic Properties of Hydroxynitrile Lyase from the Passion Fruit, Passiflora edulis: A Comparison of Natural and Recombinant Enzymes
-
A hydroxynitrile lyase from the passion fruit Passiflora edulis (PeHNL) was isolated from the leaves and showed high stability in biphasic co-organic solvent systems for cyanohydrin synthesis. Cyanohydrins are important building blocks for the production
- Nuylert, Aem,Ishida, Yuko,Asano, Yasuhisa
-
-
Read Online
- Development of a family of β-amino alcohol ligands with two stereocenters for highly efficient enantioselective trimethylsilylcyanation of aldehydes
-
The asymmetric addition of Me3SiCN to aldehydes catalyzed by titanium(IV) complexes of N-sulfonylated derivatives of β-amino alcohols gave excellent ee's up to 96% ee.
- You,Gau,Choi
-
-
Read Online
- Purification, immobilization and characterization of (R)-hydroxynitrile lyase from Prunus amygdalus turcomanica seeds and their applicability for synthesis of enantiopure cyanohydrins
-
A hydroxynitrile lyase (HNL) was purified from wild almond seeds (Prunus amygdalus turcomanica Lincz.) for the first time. Native and subunit molecular masses of the HNL were determined as 100 and 25 kDa, respectively indicating that the enzyme is a homot
- Alagoez, Dilek,Tuekel, S. Seyhan,Yildirim, Deniz
-
-
Read Online
- Enantioselective formation of mandelonitrile acetate - Investigation of a dynamic kinetic resolution
-
Investigations into the separate reactions of a dynamic kinetic resolution and the combined reactions revealed that the overall sequence is highly susceptible to the water content of the reaction mixture. While the racemization and formation of mandelonitrile as well as its kinetic resolution proceeded rapidly when performed independently, the dynamic kinetic resolution was severely hampered by the undesired formation of acetic acid during the reaction. The utilization of drying reagents and neutralizing agents in order to suppress the formation of acetic acid or its consequences were investigated.
- Li, Yu-Xin,Straathof, Adrie J.J.,Hanefeld, Ulf
-
-
Read Online
- The first hydroxynitrile lyase catalysed cyanohydrin formation in ionic liquids
-
Benzaldehyde, decanal, undecanal and dodecanal were reacted with hydrogen cyanide in a two phase solvent system aqueous buffer and ionic liquids EMIM·BF4, PMIM·BF4 and BMIM·BF 4 in the presence of the hydroxynitrile lyases from Prunus amygdalus and Hevea brasiliensis. When compared to the use of organic solvents as the nonaqueous phase, the reaction rate was significantly increased whereas the enantioselectivity remained good.
- Gaisberger, Richard P.,Fechter, Martin H.,Griengl, Herfried
-
-
Read Online
- Enzyme engineering improves catalytic efficiency and enantioselectivity of hydroxynitrile lyase for promiscuous retro-nitroaldolase activity
-
Protein engineering to improve promiscuous catalytic activity is important for biocatalytic application of enzymes in green synthesis. We uncovered the significance of binding site residues in Arabidopsis thaliana hydroxynitrile lyase (AtHNL) for promiscuous retro-nitroaldolase activity. Engineering of AtHNL has improved enantioselective retro-nitroaldolase activity, a synthetically important biotransformation, for the production of enantiopure β-nitroalcohols having absolute configuration opposite to that of the stereopreference of the HNL. The variant F179A has shown ~ 12 fold increased selectivity towards the retro-nitroaldol reaction over cyanogenesis, the natural activity of the parent enzyme. Screening of the two saturation libraries of Phe179 and Tyr14 revealed several variants with higher kcat, while F179N showed ~ 2.4-fold kcat/Km than the native enzyme towards retro-nitroaldol reaction. Variants F179N, F179M, F179W, F179V, F179I, Y14L, and Y14M have shown > 99% ee in the preparation of (S)-2-nitro-1-phenylethanol (NPE) from the racemic substrate, while F179N has shown the E value of 138 vs. 81 by the wild type. Our molecular docking and dynamics simulations (MDS) studies results provided insights into the molecular basis of higher enantioselectivity by the F179N toward the retro-nitroaldolase activity than the other mutants. Binding energy calculations also showed the higher negative binding free energy in the case of F179N-(R)-NPE compared to other complexes that support our experimental low Km by the F179N for NPE. A plausible retro-nitroaldol reaction mechanism was proposed based on the MDS study of enzyme-substrate interaction.
- Akif, Mohd.,Gilani, Rubina,Kumar Padhi, Santosh,Lata, Surabhi,Rai, Nivedita,Sreenivasa Rao, D. H.,Vishnu Priya, Badipatla
-
-
- A High-Throughput Screening Method for the Directed Evolution of Hydroxynitrile Lyase towards Cyanohydrin Synthesis
-
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
-
p. 996 - 1000
(2021/01/15)
-
- Structure-Guided Tuning of a Hydroxynitrile Lyase to Accept Rigid Pharmaco Aldehydes
-
The chiral vicinal C-O/C-N bifunctional groups generated from enzymatic hydrocyanation represents a useful methodology. However, construction of the pharmacophore of β2-adrenoreceptor agonists with this method remains a great challenge because of complete racemization of the benzylic alcohol during deprotection of the acetal groups. In this study, structure-guided redesign of a hydroxynitrile lyase originating from Prunus communis (PcHNL5) enables a highly enantioselective hydrocyanation of rigid benzo-ketal aldehyde which was proved to be resistant against racemization during the deprotection step, with dramatically improved productivity (>95% conversion vs 2-adrenoreceptor agonist, in an optically pure form (>99% ee) with an overall yield of 54%, which is the highest value reported.
- Hong, Ran,Li, Fu-Long,Lin, Guo-Qiang,Lin, Zuming,Xu, Jian-He,Yu, Hui-Lei,Zheng, Yu-Cong
-
p. 5757 - 5763
(2020/06/09)
-
- Stabilization of Hydroxynitrile Lyases from Two Variants of Passion Fruit, Passiflora edulis Sims and Passiflora edulis Forma flavicarpa, by C-Terminal Truncation
-
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
-
p. 181 - 189
(2019/12/12)
-
- Preparation method and application of a chiral Zr-MOF catalyst
-
The invention relates to a preparation method and application of a chiral Zr-MOF catalyst and belongs to the technical field of chiral catalyst preparation. The structural formula of an organic ligandL of the chiral Zr-MOF catalyst is (R)-4,4'-dimethoxyca
- -
-
-
- Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization
-
In this study, we combined photo-organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo-organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light-driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α-chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two-phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo-organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.
- Zhang, Wuyuan,Fueyo, Elena Fernandez,Hollmann, Frank,Martin, Laura Leemans,Pesic, Milja,Wardenga, Rainer,H?hne, Matthias,Schmidt, Sandy
-
supporting information
p. 80 - 84
(2019/01/04)
-
- Hydroxynitrile lyases covalently immobilized in continuous flow microreactors
-
Enzymes are supreme catalysts when it comes to high enantiopurities and their immobilization will pave the way for continuous operation. In this context, we show the covalent immobilization of hydroxynitrile lyases HbHNL (from Hevea brasiliensis) and MeHN
- Van Der Helm, Michelle P.,Bracco, Paula,Busch, Hanna,Szymańska, Katarzyna,Jarz?bski, Andrzej B.,Hanefeld, Ulf
-
p. 1189 - 1200
(2019/03/12)
-
- Preparation of chitosan-supported urea materials and their application in some organocatalytic procedures
-
An efficient and mild procedure was developed for the preparation of three chitosan-supported ureas containing electron-withdrawing groups. These catalysts were characterized and employed as organocatalysts in different transformations, including the enan
- de Gonzalo, Gonzalo,Franconetti, Antonio,Fernández, Rosario,Lassaletta, José M.,Cabrera-Escribano, Francisca
-
p. 365 - 374
(2018/07/25)
-
- Controlled Exchange of Achiral Linkers with Chiral Linkers in Zr-Based UiO-68 Metal-Organic Framework
-
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.
- Tan, Chunxia,Han, Xing,Li, Zijian,Liu, Yan,Cui, Yong
-
p. 16229 - 16236
(2018/11/27)
-
- Multivariate Metal-Organic Frameworks as Multifunctional Heterogeneous Asymmetric Catalysts for Sequential Reactions
-
The search for versatile heterogeneous catalysts with multiple active sites for broad asymmetric transformations has long been of great interest, but it remains a formidable synthetic challenge. Here we demonstrate that multivariate metal-organic frameworks (MTV-MOFs) can be used as an excellent platform to engineer heterogeneous catalysts featuring multiple and cooperative active sites. An isostructural series of 2-fold interpenetrated MTV-MOFs that contain up to three different chiral metallosalen catalysts was constructed and used as efficient and recyclable heterogeneous catalysts for a variety of asymmetric sequential alkene epoxidation/epoxide ring-opening reactions. Interpenetration of the frameworks brings metallosalen units adjacent to each other, allowing cooperative activation, which results in improved efficiency and enantioselectivity over the sum of the individual parts. The fact that manipulation of molecular catalysts in MTV-MOFs can control the activities and selectivities would facilitate the design of novel multifunctional materials for enantioselective processes.
- Xia, Qingchun,Li, Zijian,Tan, Chunxia,Liu, Yan,Gong, Wei,Cui, Yong
-
supporting information
p. 8259 - 8266
(2017/06/28)
-
- Hydroxynitrile Lyase Isozymes from Prunus communis: Identification, Characterization and Synthetic Applications
-
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
-
supporting information
p. 1185 - 1193
(2017/04/13)
-
- An orthogonal biocatalytic approach for the safe generation and use of HCN in a multistep continuous preparation of chiral O-acetylcyanohydrins
-
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
-
p. 262 - 266
(2016/01/20)
-
- Fusion of a Coiled-Coil Domain Facilitates the High-Level Production of Catalytically Active Enzyme Inclusion Bodies
-
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
-
p. 142 - 152
(2016/01/25)
-
- Enantioselective cyanosilylation of aldehydes catalyzed by a multistereogenic salen-Mn(III) complex with a rotatable benzylic group as a helping hand
-
A multistereogenic salen-Mn(iii) complex bearing an aromatic pocket and two benzylic groups as helping hands was found to be efficient in the catalysis of asymmetric cyanosilylation. The salen-Mn catalyst partially mimics the functions of biocatalysts by
- Wei, Yun-Long,Huang, Wei-Sheng,Cui, Yu-Ming,Yang, Ke-Fang,Xu, Zheng,Xu, Li-Wen
-
p. 3098 - 3103
(2015/02/02)
-
- Improving the properties of bacterial r-selective hydroxynitrile lyases for industrial applications
-
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
-
p. 325 - 332
(2015/03/05)
-
- (R)-selective hydroxynitrile lyase variants with a cupin fold having improved substrate scope and the use thereof
-
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
- -
-
Paragraph 0074-0077
(2015/12/31)
-
- Discovery and molecular and biocatalytic properties of hydroxynitrile lyase from an invasive millipede, Chamberlinius hualienensis
-
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
- Dadashipour, Mohammad,Ishida, Yuko,Yamamoto, Kazunori,Asano, Yasuhisa
-
p. 10605 - 10610
(2015/09/07)
-
- Substrate evaluation of rhodococcus erythropolis SET1, a nitrile hydrolysing bacterium, demonstrating dual activity strongly dependent on nitrile sub-structure
-
Assessment of Rhodococcus erythropolis SET1, a novel nitrile hydrolysing bacterial isolate, has been undertaken with 34 nitriles, 33 chiral and 1 prochiral. These substrates consist primarily of β-hydroxy nitriles with varying alkyl and aryl groups at the β position and containing in several compounds different substituents α to the nitrile. In the case of β-hydroxy nitriles without substitution at the α position, acids were the major products obtained, along with recovered nitrile after biotransformation, as a result of suspected nitrilase activity of the isolate. Unexpectedly, amides were found to be the major hydrolysis product when the β-hydroxy nitriles possessed a vinyl group at this position. To probe this behaviour further, additional related substrates were evaluated containing electron-withdrawing groups at the α position, and amide was also observed upon biotransformation in the presence of SET1. Therefore this novel isolate has also demonstrated NHase activity with nitriles that appears to be substrate-dependent.
- Coady, Tracey M.,Coffey, Lee V.,O'Reilly, Catherine,Lennon, Claire M.
-
supporting information
p. 1108 - 1116
(2015/02/19)
-
- Chemoenzymatic flow cascade for the synthesis of protected mandelonitrile derivatives
-
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.
-
supporting information
p. 1634 - 1638
(2015/03/05)
-
- Enantioselective cyanosilylation of aldehydes catalyzed by novel camphor derived Schiff bases-titanium(IV) complexes
-
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
-
p. 554 - 562
(2014/05/06)
-
- Chemoenzymatic asymmetric synthesis of fluoxetine, atomoxetine, nisoxetine, and duloxetine
-
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.
- Rej, Rohan Kalyan,Das, Tapas,Hazra, Suman,Nanda, Samik
-
p. 913 - 918
(2013/09/23)
-
- One-step preparation of O-(α-bromoacyl) cyanohydrins by minor enantiomer recycling: Synthesis of 4-amino-2(5H)-furanones
-
O-(α-Bromoacyl) cyanohydrins were prepared in a single step from a range of different aldehydes in combination with α-bromoacyl cyanides. By the use of a cyclic procedure where the two minor diastereoisomers from a chiral Lewis acid-catalyzed reaction und
- Hertzberg, Robin,Moberg, Christina
-
p. 9174 - 9180
(2013/10/08)
-
- A simple separation method for (S)-hydroxynitrile lyase from cassava and its application in asymmetric cyanohydrination
-
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
-
p. 434 - 439
(2013/06/27)
-
- A novel bifunctional Ti(IV) complex catalyzed asymmetric silylcyanation of aldehydes
-
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
-
-
- α-Pinene-type chiral Schiff bases as tridentate ligands in asymmetric addition reactions
-
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
-
experimental part
p. 648 - 657
(2011/07/08)
-
- Unsymmetric salen ligands bearing a Lewis base: Intramolecularly cooperative catalysis for cyanosilylation of aldehydes
-
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
-
supporting information; experimental part
p. 6323 - 6330
(2011/10/09)
-
- Highly active bifunctional salenTi(IV) catalysts for asymmetric cyanosilylation of aldehydes and TMSCN
-
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
-
scheme or table
p. 1285 - 1288
(2012/01/17)
-
- Enantioselective silylcyanation of aldehydes catalyzed by new chiral oxovanadium complex
-
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
-
scheme or table
p. 1981 - 1984
(2012/03/10)
-
- Enantioselective hydrocyanation of aldehydes catalyzed by [Li{Ru(phgly)2(binap)}]X (X = Cl, Br)
-
Novel bimetallic complexes [Li{Ru[(S)-phgly]2[(S)-binap]}]X (X = Cl, Br) are readily synthesized by mixing Ru[(S)-phgly]2[(S)-binap] and LiX. A single-crystal X-ray analysis reveals the structure. These bimetallic complexes efficient
- Kurono, Nobuhito,Yoshikawa, Tatsuya,Yamasaki, Mikio,Ohkuma, Takeshi
-
supporting information; experimental part
p. 1254 - 1257
(2011/05/02)
-
- Hydroxynitrile lyase from Arabidopsis thaliana: Identification of reaction parameters for enantiopure cyanohydrin synthesis by pure and immobilized catalyst
-
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
-
experimental part
p. 2399 - 2408
(2011/11/06)
-
- Enantioselective O-acetylcyanation/cyanoformylation of aldehydes using catalysts with built-in crown ether-like motif in chiral macrocyclic V(V) salen complexes
-
Chiral macrocyclic V(V) salen complexes 1a-f derived from macrocyclic ligands obtained by the reaction of 1R,2R-(-) diaminocyclohexane/(1R,2R)-(+)-1, 2-diphenylethylenediamine with bis-aldehydes 2 and 3 were synthesized and used as efficient catalysts in asymmetric cyanation reactions. The V(V) catalysts demonstrated excellent performance (product yields and ees up to 99%) with potassium cyanide (KCN) and sodium cyanide (NaCN). The catalytic system also performed very well with a safer source of cyanide-ethyl cyanoformate to give cyanohydrin carbonates in excellent yield and ee (up to 97%). The V(V) macrocyclic salen complex 1b retained its performance at multi-gram level and was conveniently recycled for a number of times.
- Khan, Noor-Ul H.,Sadhukhan, Arghya,Maity, Nabin C.,Kureshy, Rukhsana I.,Abdi, Sayed H.R.,Saravanan,Bajaj, Hari C.
-
body text
p. 7073 - 7080
(2011/10/07)
-
- Enzymatic kinetic resolution of racemic cyanohydrins via enantioselective acylation
-
Enzymatic kinetic resolution of a series of aromatic and aliphatic cyanohydrins in organic media has been investigated. The behavior of potential lipases, molecular sieves, acyl reagent, reaction temperature, and organic solvents on the kinetic resolution was studied. The influence of substrate structure, steric, and electronic nature and position of the aryl substituent on the enantioselectivity was discussed. Under the optimized reaction conditions, good enantioselectivity could be achieved for most of the investigated compounds. Specifically, substrates 1a, 1c, 1d, 1f, 1u could be resolved with the kinetic enantiomer ratio (E) higher than 200.
- Xu, Qing,Xie, Yongli,Geng, Xiaohong,Chen, Peiran
-
experimental part
p. 624 - 630
(2010/09/07)
-
- Room-temperature synthesis of enantioenriched non-protected cyanohydrins using vanadium(salalen) catalyst
-
Room-temperature synthesis of enantioenriched non-protected cyanohydrins using acetone cyanohydrin as the cyanide source was achieved by V(salalen) catalyst. Aliphatic aldehydes underwent the cyanation with 89-95% ee in the presence of only 0.2-0.4 mol% catalyst. Aromatic cyanohydrins were also obtained in high enantiomeric excesses under modified conditions.
- Sakai, Yoshifumi,Mitote, Junko,Matsumoto, Kazuhiro,Katsuki, Tsutomu
-
supporting information; experimental part
p. 5787 - 5789
(2010/09/05)
-
- Asymmetric synthesis of a new salen type-titanium complex as the catalyst for asymmetric trimethylsilylcyanation of aldehydes
-
This work describes the asymmetric synthesis of a new salen-type ligand via a Diels-Alder reaction and Curtius rearrangement. The ligand with a norbornane skeleton was used in the trimethylsilylcyanation of aldehydes, but the enantioselectivity was 55%ee. The norborane skeleton was cleaved to destroy this rigidity, and the eanatioselectivity was thereby increased to 85%ee.
- Lin, Zheng-Chang,Chen, Chinpiao
-
scheme or table
p. 726 - 737
(2011/04/23)
-
- Investigation of lewis acid versus lewis base catalysis in asymmetric cyanohydrin synthesis
-
The asymmetric addition of trimethylsilyl cyanide to aldehydes can be catalysed by Lewis acids and/or Lewis bases, which activate the aldehyde and trimethylsilyl cyanide, respectively. It is not always apparent from the structure of the catalyst whether Lewis acid or Lewis base catalysis predominates. To investigate this in the context of using salen complexes of titanium, vanadium and aluminium as catalysts, a Hammett analysis of asymmetric cyanohydrin synthesis was undertaken. When Lewis acid catalysis is dominant, a significantly positive reaction constant is observed, whereas reactions dominated by Lewis base catalysis give much smaller reaction constants. [{Ti(salen)O}2] was found to show the highest degree of Lewis acid catalysis, whereas two [VO(salen)X] (X = EtOSO3 or NCS) complexes both displayed lower degrees of Lewis acid catalysis. In the case of reactions catalysed by [{Al(salen)}2O] and triphenyl- phosphine oxide, a non-linear Ham- mett plot was observed, which is indicative of a change in mechanism with increasing Lewis base catalysis as the carbonyl compound becomes more electron-deficient. These results suggested that the aluminium complex/tri- phenylphosphine oxide catalyst system should also catalyse the asymmetric addition of trimethylsilyl cyanide to ke- tones and this was found to be the case.
- North, Michael,Omedes-Pujol, Marta,Williamson, Courtney
-
experimental part
p. 11367 - 11375
(2010/11/17)
-