Biocatalytic synthesis of enantiopure building blocks for pharmaceuticals.

Biocatalytic transformations have emerged as a viable alternative to other asymmetric chemical methods due to the intrinsic high stereoselectivity of the enzymes and the mild reaction conditions. Just a decade ago, the reaction scope of applicable biotransformations for organic synthesis was limited to a handful of reaction types. Tremendous progress has been made in the meantime so that this review presents only a small selection of the broad range of possible biotransfromations for organic synthesis available today. Lyases (hydroxynitrile lyase, aldolases) and redox enzymes like alcohol dehydrogenases, Baeyer–Villiger monooxygenase, dioxygenases, ene reductases, berberine bridge enzyme and v-transaminases are discussed besides hydrolases.

[1]  Oliver May,et al.  Biocatalytic Reductions: From Lab Curiosity to “First Choice” , 2008 .

[2]  E. Busto,et al.  Hydrolases: catalytically promiscuous enzymes for non-conventional reactions in organic synthesis. , 2010, Chemical Society reviews.

[3]  D. Hilvert,et al.  Chemoenzymatic synthesis of differentially protected 3-deoxysugars , 2010, Nature Chemistry.

[4]  Joerg H. Schrittwieser,et al.  Biocatalytic enantioselective oxidative C-C coupling by aerobic C-H activation. , 2011, Angewandte Chemie.

[5]  John Andraos,et al.  Several generations of chemoenzymatic synthesis of oseltamivir (Tamiflu): evolution of strategy, quest for a process-quality synthesis, and evaluation of efficiency metrics. , 2011, The Journal of organic chemistry.

[6]  Karen Robins,et al.  Rational assignment of key motifs for function guides in silico enzyme identification. , 2010, Nature chemical biology.

[7]  I. Arends,et al.  Enzymatic reductions for the chemist , 2011 .

[8]  J. Pietruszka,et al.  Ene Reductase‐Catalysed Synthesis of (R)‐Profen Derivatives , 2012 .

[9]  Joerg H. Schrittwieser,et al.  Biocatalytic Organic Synthesis of Optically Pure (S)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids , 2011, The Journal of organic chemistry.

[10]  W. Kroutil,et al.  Chemoenzymatic Asymmetric Total Synthesis of (S)‐Rivastigmine Using ω‐Transaminases. , 2010 .

[11]  Jack Liang,et al.  Highly Enantioselective Reduction of a Small Heterocyclic Ketone: Biocatalytic Reduction of Tetrahydrothiophene-3-one to the Corresponding (R)-Alcohol , 2010 .

[12]  Wolfgang Kroutil,et al.  omega-Transaminases for the synthesis of non-racemic alpha-chiral primary amines. , 2010, Trends in biotechnology.

[13]  John H. Grate,et al.  A green-by-design biocatalytic process for atorvastatin intermediate , 2010 .

[14]  B. H. Chen,et al.  A Multidisciplinary Approach Toward the Rapid and Preparative-Scale Biocatalytic Synthesis of Chiral Amino Alcohols: A Concise Transketolase-/omega-Transaminase-Mediated Synthesis of (2S,3S)-2-Aminopentane-1,3-diol , 2010 .

[15]  N. Turner,et al.  A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions. , 2010, Chemical communications.

[16]  A. Demain,et al.  Enzymes and Bioconversions of Industrial, Pharmaceutical, and Biotechnological Significance , 2011 .

[17]  D. Nelson,et al.  A new dehydrogenase from Clostridium acetobutylicum for asymmetric synthesis: dynamic reductive kinetic resolution entry into the Taxotère side chain. , 2011, Chemical communications.

[18]  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.

[19]  J. Pietruszka,et al.  Chemoenzymatic Synthesis of (Protected) Psymberic Acid , 2009 .

[20]  F. G. Mutti,et al.  Stereoselectivity of Four (R)‐Selective Transaminases for the Asymmetric Amination of Ketones , 2011 .

[21]  M. Fraaije,et al.  Dynamic kinetic resolution of α-substituted β-ketoesters catalyzed by Baeyer-Villiger monooxygenases: access to enantiopure α-hydroxy esters. , 2011, Angewandte Chemie.

[22]  N. Turner Deracemisation methods. , 2010, Current opinion in chemical biology.

[23]  Chi-Huey Wong,et al.  Enzymes in the synthesis of glycoconjugates. , 2011, Chemical reviews.

[24]  J. Bäckvall,et al.  Enantioselective enzymatic desymmetrization of prochiral allenic diols. , 2011, Angewandte Chemie.

[25]  N. Turner,et al.  Highly stereoselective synthesis of substituted prolyl peptides using a combination of biocatalytic desymmetrization and multicomponent reactions. , 2010, Angewandte Chemie.

[26]  Vesna Mitchell,et al.  Development of a Biocatalytic Process as an Alternative to the (−)-DIP-Cl-Mediated Asymmetric Reduction of a Key Intermediate of Montelukast , 2010 .

[27]  Jian‐He Xu,et al.  Highly efficient synthesis of chiral alcohols with a novel NADH-dependent reductase from Streptomyces coelicolor. , 2011, Bioresource technology.

[28]  J. Pietruszka,et al.  Key building blocks via enzyme-mediated synthesis. , 2010, Topics in current chemistry.

[29]  A. Träff,et al.  A chemoenzymatic dynamic kinetic resolution approach to enantiomerically pure (R)- and (S)-duloxetine. , 2011, The Journal of organic chemistry.

[30]  Nicholas J. Turner,et al.  Efficient Production of Enantiomerically Pure Chiral Amines at Concentrations of 50 g/L Using Transaminases , 2010 .

[31]  Wolfgang Kroutil,et al.  Recent biocatalytic oxidation–reduction cascades , 2011, Current opinion in chemical biology.

[32]  U. Hanefeld,et al.  Enantioselective Enzyme-Catalysed Synthesis of Cyanohydrins , 2009 .

[33]  S. Kambourakis,et al.  Diarylketone Ketoreductase Screen and Synthesis Demonstration to Access mGlu2 Receptor Potentiators , 2011 .

[34]  Wolfgang Kroutil,et al.  Chemoenzymatic asymmetric total synthesis of (S)-Rivastigmine using omega-transaminases. , 2010, Chemical communications.

[35]  Paul N. Devine,et al.  Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture , 2010, Science.

[36]  Roger M. Howard,et al.  Application of biocatalysis towards asymmetric reduction and hydrolytic desymmetrisation in the synthesis of a β-3 receptor agonist , 2011 .

[37]  Kurt Faber,et al.  Asymmetric Synthesis of (R)‐3‐Hydroxy‐2‐methylpropanoate (‘Roche Ester’) and Derivatives via Biocatalytic CC‐Bond Reduction , 2010 .

[38]  Ramesh N. Patel Biocatalysis: Synthesis of Key Intermediates for Development of Pharmaceuticals , 2011 .