One-pot Biocatalytic Cascade Reduction of Cyclic Enimines for the Preparation of Diastereomerically Enriched N-Heterocycles.

Ene-reductases (EREDs) catalyse the reduction of electron-deficient C=C bonds. Herein, we report the first example of ERED-catalysed net reduction of C=C bonds of enimines (α,β-unsaturated imines). Preliminary studies suggest their hydrolysed ring-open ω-amino enones are the likely substrates for this step. When combined with imine reductase (IRED)-mediated C=N reduction, the result is an efficient telescoped sequence for the preparation of diastereomerically enriched 2-substituted saturated amine heterocycles.

[1]  Nigel S. Scrutton,et al.  Discovery, Characterisation, Engineering and Applications of Ene Reductases for Industrial Biocatalysis. , 2018, ACS catalysis.

[2]  Peiyuan Yao,et al.  Imine Reductase‐Catalyzed Enantioselective Reduction of Bulky α,β‐Unsaturated Imines en Route to a Pharmaceutically Important Morphinan Skeleton , 2018, Advanced Synthesis & Catalysis.

[3]  N. Turner,et al.  Chemoenzymatic Synthesis of Substituted Azepanes by Sequential Biocatalytic Reduction and Organolithium-Mediated Rearrangement. , 2018, Journal of the American Chemical Society.

[4]  Nicholas J. Turner,et al.  Synthesis of 2,5‐Disubstituted Pyrrolidine Alkaloids via A One‐Pot Cascade Using Transaminase and Reductive Aminase Biocatalysts , 2018, ChemCatChem.

[5]  H. Gröger,et al.  Enantioselective reduction of sulfur-containing cyclic imines through biocatalysis , 2018, Nature Communications.

[6]  N. Scrutton,et al.  Correction to “Discovery, Characterization, Engineering and Applications of Ene-Reductases for Industrial Biocatalysis” , 2018 .

[7]  C. Méndez,et al.  New Insights into the Biosynthesis Pathway of Polyketide Alkaloid Argimycins P in Streptomyces argillaceus , 2018, Front. Microbiol..

[8]  Lisa Jarvis,et al.  The year in new drugs , 2018 .

[9]  Nicholas J Turner,et al.  Biocatalytic Routes to Enantiomerically Enriched Dibenz[c,e]azepines. , 2017, Angewandte Chemie.

[10]  Benjamin R. Lichman,et al.  Enzyme catalysed Pictet-Spengler formation of chiral 1,1'-disubstituted- and spiro-tetrahydroisoquinolines , 2017, Nature Communications.

[11]  Elaine O’Reilly,et al.  Transaminase Triggered Aza-Michael Approach for the Enantioselective Synthesis of Piperidine Scaffolds. , 2016, Journal of the American Chemical Society.

[12]  Nicholas J. Turner,et al.  One-Pot Cascade Synthesis of Mono- and Disubstituted Piperidines and Pyrrolidines using Carboxylic Acid Reductase (CAR), ω-Transaminase (ω-TA), and Imine Reductase (IRED) Biocatalysts , 2016 .

[13]  N. Turner,et al.  An (R)‐Imine Reductase Biocatalyst for the Asymmetric Reduction of Cyclic Imines , 2015, ChemCatChem.

[14]  Elisabetta Brenna,et al.  Enantioselective Synthesis of (R)‐2‐Arylpropanenitriles Catalysed by Ene‐Reductases in Aqueous Media and in Biphasic Ionic Liquid–Water Systems , 2014 .

[15]  N. Turner,et al.  Development of an R‐Selective Amine Oxidase with Broad Substrate Specificity and High Enantioselectivity , 2014 .

[16]  Nicholas J Turner,et al.  A Regio- and Stereoselective ω-Transaminase/Monoamine Oxidase Cascade for the Synthesis of Chiral 2,5-Disubstituted Pyrrolidines , 2014, Angewandte Chemie.

[17]  N. Turner,et al.  Asymmetric Reduction of Cyclic Imines Catalyzed by a Whole‐Cell Biocatalyst Containing an (S)‐Imine Reductase , 2013 .

[18]  E. Magalhaes,et al.  About the Royal Society of Chemistry , 2013 .

[19]  Joerg H. Schrittwieser,et al.  The role of biocatalysis in the asymmetric synthesis of alkaloids , 2013, RSC advances.

[20]  M. Hall,et al.  Unusual reactions mediated by FMN-dependent ene- and nitro-reductases , 2013 .

[21]  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 .

[22]  A. Mann,et al.  Synthesis and biological evaluation of desmethylveramiline, a micromolar Hedgehog inhibitor. , 2011, Bioorganic & medicinal chemistry letters.

[23]  A. Bommarius,et al.  Asymmetric bioreduction of alkenes using ene-reductases YersER and KYE1 and effects of organic solvents. , 2011, Organic letters.

[24]  Virginie Mouriès‐Mansuy,et al.  Total synthesis of quinolizidine (-)-217A. , 2010, The Journal of organic chemistry.

[25]  H. Suga,et al.  Total Synthesis of (.+-.)-Quinolizidine 217A. , 2010 .

[26]  Bernhard Hauer,et al.  The Substrate Spectra of Pentaerythritol Tetranitrate Reductase, Morphinone Reductase, N‐Ethylmaleimide Reductase and Estrogen‐Binding Protein in the Asymmetric Bioreduction of Activated Alkenes , 2010 .

[27]  J. Stewart,et al.  Site-saturation mutagenesis of tryptophan 116 of Saccharomyces pastorianus old yellow enzyme uncovers stereocomplementary variants. , 2009, Journal of the American Chemical Society.

[28]  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.

[29]  C. A. Austin,et al.  Stereodivergent Diversity Oriented Synthesis of Piperidine Alkaloids , 2006 .

[30]  R. Pike,et al.  A one-pot process for the enantioselective synthesis of amines via reductive amination under transfer hydrogenation conditions. , 2003, Organic letters.