Enantioselective Synthesis of (R)‐2‐Arylpropanenitriles Catalysed by Ene‐Reductases in Aqueous Media and in Biphasic Ionic Liquid–Water Systems

The enantioselective reduction of α‐methylene nitrile derivatives catalysed by ene‐reductases affords the corresponding (R)‐2‐arylpropanenitriles with high conversion values. The reaction is investigated either in aqueous medium (with an organic cosolvent or by loading the substrate onto hydrophobic resins) or in a biphasic ionic liquid–water system. The use of ionic liquids, herein with isolated ene‐reductases, is found to improve the work‐up and the substrate recovery method. The synthetic manipulation of the final chiral nitrile derivatives indicates how this biocatalysed method can be exploited for the preparation of a wide range of chiral compounds.

[1]  R. Csuk,et al.  Baker's yeast mediated transformations in organic chemistry , 1991 .

[2]  A. Smallridge,et al.  The baker's yeast-mediated reduction of conjugated methylene groups in an organic solvent , 2001 .

[3]  R. Mccague,et al.  Asymmetric hydrogenation of a 4,4-diaryl-3-butenoate; a novel approach to sertraline. , 2003, Organic & biomolecular chemistry.

[4]  F. Fleming,et al.  Nitrile-containing pharmaceuticals: efficacious roles of the nitrile pharmacophore. , 2010, Journal of medicinal chemistry.

[5]  N. Scrutton,et al.  Biocatalytic Reductions and Chemical Versatility of the Old Yellow Enzyme Family of Flavoprotein Oxidoreductases , 2010 .

[6]  Muhammad Moniruzzaman,et al.  Recent advances of enzymatic reactions in ionic liquids , 2010 .

[7]  B. Hauer,et al.  Asymmetric Bioreduction of Activated C=C Bonds Using Zymomonas mobilis NCR Enoate Reductase and Old Yellow Enzymes OYE 1–3 from Yeasts , 2008 .

[8]  P. James,et al.  ChemInform Abstract: Immobilized Baker′s Yeast Reduction of Ketones in an Ionic Liquid, [bmim]PF6 and Water Mix. , 2001 .

[9]  L. Greiner,et al.  Ionic liquids in biotechnology: applications and perspectives for biotransformations , 2008, Applied Microbiology and Biotechnology.

[10]  J. Lepoittevin,et al.  Approach to the stereoselective synthesis of (R)- and (S)-4-methoxydalbergione via asymmetric catalytic hydrogenation , 1995 .

[11]  G. C. Fu,et al.  Catalytic asymmetric synthesis of secondary nitriles via stereoconvergent Negishi arylations and alkenylations of racemic α-bromonitriles. , 2012, Journal of the American Chemical Society.

[12]  P. Dauban,et al.  N2-benzyl-N1-(1-(1-naphthyl)ethyl)-3-phenylpropane-1,2-diamines and conformationally restrained indole analogues: development of calindol as a new calcimimetic acting at the calcium sensing receptor. , 2004, Bioorganic & medicinal chemistry letters.

[13]  J. Kunitomo,et al.  Synthesis, structure-activity relationship, and pharmacological studies of novel melanin-concentrating hormone receptor 1 antagonists 3-aminomethylquinolines: reducing human ether-a-go-go-related gene (hERG) associated liabilities. , 2012, Journal of medicinal chemistry.

[14]  J. Yun,et al.  Highly enantioselective conjugate reduction of beta,beta-disubstituted alpha,beta-unsaturated nitriles. , 2006, Angewandte Chemie.

[15]  Zaira Maugeri,et al.  Ionic liquids in biotransformations: from proof-of-concept to emerging deep-eutectic-solvents. , 2011, Current opinion in chemical biology.

[16]  J. Yun,et al.  Highly Enantioselective Conjugate Reduction of β,β‐Disubstituted α,β‐Unsaturated Nitriles , 2006 .

[17]  F. Parmeggiani,et al.  On the stereochemistry of the Baker's Yeast-mediated reduction of regioisomeric unsaturated aldehydes: Examples of enantioselectivity switch promoted by substrate-engineering , 2012 .

[18]  F. Parmeggiani,et al.  Enantioselective CC bond reduction of unsaturated α-chloro esters by old yellow enzymes , 2011 .

[19]  C. Fuganti.  Baker's yeast mediated synthesis of natural products , 1990 .

[20]  S. Miller,et al.  Binding and reactivity of Candida albicans estrogen binding protein with steroid and other substrates. , 1998, Biochemistry.

[21]  D. Weuster‐Botz,et al.  Water immiscible ionic liquids as solvents for whole cell biocatalysis. , 2006, Journal of biotechnology.

[22]  Dirk Weuster-Botz,et al.  Efficient whole-cell biotransformation in a biphasic ionic liquid/water system. , 2004, Angewandte Chemie.

[23]  I. Raheem,et al.  Sustainable practices in medicinal chemistry: current state and future directions. , 2013, Journal of medicinal chemistry.

[24]  N. Scrutton,et al.  Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation. , 2009, Advanced synthesis & catalysis.

[25]  Joyram Guin,et al.  Catalytic asymmetric protonation of silyl ketene imines. , 2013, Journal of the American Chemical Society.

[26]  F. Parmeggiani,et al.  Steric Effects on the Stereochemistry of Old Yellow Enzyme-Mediated Reductions of Unsaturated Diesters: Flipping of the Substrate within the Enzyme Active Site Induced by Structural Modifications , 2012 .

[27]  K. Faber,et al.  Chemoenzymatic Asymmetric Synthesis of Pregabalin Precursors via Asymmetric Bioreduction of β-Cyanoacrylate Esters Using Ene-Reductases , 2013, The Journal of organic chemistry.

[28]  Katrina Sleeman,et al.  Structure-based design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like protease. , 2009, Journal of medicinal chemistry.

[29]  Elisabetta Brenna,et al.  Cascade Coupling of Ene Reductases with Alcohol Dehydrogenases: Enantioselective Reduction of Prochiral Unsaturated Aldehydes , 2012 .

[30]  F. Parmeggiani,et al.  Synthetic Strategies Based on CC Bioreductions for the Preparation of Biologically Active Molecules , 2013 .

[31]  S. Chakraborty,et al.  Old Yellow enzyme: aromatization of cyclic enones and the mechanism of a novel dismutation reaction. , 1995, Biochemistry.

[32]  A. Buschauer,et al.  Enantioselective hydrogenation of diaryl-substituted α,β-unsaturated nitriles , 2006 .

[33]  Bernhard Hauer,et al.  Asymmetric bioreduction of activated C=C bonds using enoate reductases from the old yellow enzyme family. , 2007, Current opinion in chemical biology.

[34]  D. Rognan,et al.  N1-Benzoyl-N2-[1-(1-naphthyl)ethyl]-trans-1,2-diaminocyclohexanes: Development of 4-chlorophenylcarboxamide (calhex 231) as a new calcium sensing receptor ligand demonstrating potent calcilytic activity. , 2006, Journal of medicinal chemistry.

[35]  Paul N. Devine,et al.  Asymmetric bioreduction of α,β-unsaturated nitriles and ketones , 2008 .

[36]  M. Faul,et al.  Practical synthesis of a vanilloid receptor-1 antagonist. , 2008, The Journal of organic chemistry.

[37]  Udo Kragl,et al.  Use of an ionic liquid in a two-phase system to improve an alcohol dehydrogenase catalysed reduction. , 2004, Chemical communications.

[38]  D. Thiele,et al.  The cloning and expression of a gene encoding Old Yellow Enzyme from Saccharomyces carlsbergensis. , 1991, The Journal of biological chemistry.

[39]  F. Parmeggiani,et al.  Productivity enhancement of C=C bioreductions by coupling the in situ substrate feeding product removal technology with isolated enzymes. , 2012, Chemical communications.

[40]  Masakazu Atobe,et al.  Nucleophilic addition of methyllithium to chiral oxime ethers: asymmetric preparation of 1-(aryl)ethylamines and application to a synthesis of calcimimetics (+)-NPS R-568 and its thio analogue , 2001 .

[41]  F. Parmeggiani,et al.  Biocatalyzed Enantioselective Reduction of Activated C=C Bonds: Synthesis of Enantiomerically Enriched α-Halo-β-arylpropionic Acids , 2011 .

[42]  N. Khiar,et al.  N-isopropylsulfinylimines as useful intermediates in the synthesis of chiral amines: expeditive asymmetric synthesis of the calcimimetic (+)-NPS R-568. , 2008, The Journal of organic chemistry.

[43]  Nigel S. Scrutton,et al.  Enzyme engineering toolbox – a ‘catalyst’ for change , 2013 .

[44]  S. Servi.  Baker's Yeast as a Reagent in Organic Synthesis , 1990 .

[45]  R. Sheldon,et al.  Biocatalysis in ionic liquids. , 2007, Chemical reviews.

[46]  K. Jitsukawa,et al.  Environmentally friendly one-pot synthesis of alpha-alkylated nitriles using hydrotalcite-supported metal species as multifunctional solid catalysts. , 2006, Chemistry.

[47]  P. Moran,et al.  Enhancements of enantio and diastereoselectivities in reduction of (Z)-3-halo-4-phenyl-3-buten-2-one mediated by microorganisms in ionic liquid/water biphasic system , 2013 .

[48]  Elisabetta Brenna,et al.  Enoate Reductase-Mediated Preparation of Methyl (S)-2-Bromobutanoate, a Useful Key Intermediate for the Synthesis of Chiral Active Pharmaceutical Ingredients , 2012 .

[49]  N. Bruce,et al.  'New uses for an Old Enzyme'--the Old Yellow Enzyme family of flavoenzymes. , 2002, Microbiology.

[50]  C. Bigogno,et al.  Aryltriflates as a Neglected Moiety in Medicinal Chemistry: A Case Study from a Lead Optimization of CXCL8 Inhibitors. , 2011, ACS medicinal chemistry letters.

[51]  F. Parmeggiani,et al.  Old Yellow Enzyme-mediated reduction of β-cyano-α,β-unsaturated esters for the synthesis of chiral building blocks: stereochemical analysis of the reaction , 2013 .

[52]  Lei Liu,et al.  Synthesis of α-aryl nitriles through palladium-catalyzed decarboxylative coupling of cyanoacetate salts with aryl halides and triflates. , 2011, Angewandte Chemie.

[53]  F. Srienc,et al.  Toward advanced ionic liquids. Polar, enzyme-friendly solvents for biocatalysis , 2010, Biotechnology and bioprocess engineering : BBE.

[54]  F. Cunha,et al.  Blockade of the chemokine receptor CXCR2 ameliorates adjuvant‐induced arthritis in rats , 2008, British journal of pharmacology.