Biocatalytic Reduction Reactions from a Chemist's Perspective

Abstract

Reductions play a key role in organic synthesis, producing chiral products with new functionalities. Enzymes can catalyse such reactions with exquisite stereo‐, regio‐ and chemoselectivity, leading the way to alternative shorter classical synthetic routes towards not only high‐added‐value compounds but also bulk chemicals. In this review we describe the synthetic state‐of‐the‐art and potential of enzymes that catalyse reductions, ranging from carbonyl, enone and aromatic reductions to reductive aminations.

Power of Biocatalysis for Organic Synthesis

“… 101 − 106 The latter was obtained in a classical synthetic route. In addition to the synthetically very well established hydrolases, further types of enzymes are commonly applied in synthesis, including alcohol dehydrogenases (performing the stereoselective reduction of carbonyls), 107 − 112 transaminases (TAs), imine reductases (IREDs), and reductive aminases (RedAm’s) (catalyzing reductive aminations). 113 − 115 In contrast with hydrolases applied in resolution reactions, these enzymes allow the direct asymmetric synthesis of enantiopure alcohols and amines in one step.…”

“…However, the mentioned catalysts represent just a fraction of the synthetic versatility of biocatalysis, which offers a variety of further well-developed and synthetically characterized enzymatic transformations, including C–C bond formations, 116 − 119 selective CH functionalization reactions, 120 − 123 and novel chemo- and regioselective redox reactions. 107 , 124 In the subsequent sections, a selection of representative examples of biocatalytic transformations is provided.…”

Biocatalyzed Redox Processes Employing Green Reaction Media

“…Among the six different types of biocatalysts according to the type of reaction they catalyze, oxidoreductases (EC 1) are, together with hydrolases, the most employed family of enzymes with synthetic purposes. This large group of enzymes, with 22 types of oxidoreductase subtypes, are involved in all type of redox reactions, catalyzing oxidation and reductions processes [ 8 , 9 , 10 , 11 ]. The application of oxidoreductases to obtain valuable building blocks is a current area of interest in organic synthesis, due to the mild reaction conditions and oxidants/reductants required for their function, combined with the generally exquisite stereoselectivity afforded by this type of catalysts.…”

Engineering of Saccharomyces pastorianus Old Yellow Enzyme 1 for the Synthesis of Pharmacologically Active (S)-Profen Derivatives

“…Ene reductases (EREDs), which catalyze the reduction of activated C=C bonds and thus generate two chiral centers, are powerful and valuable biocatalysts in asymmetric synthesis. [1][2][3][4][5] Among the families of EREDs, the prototypical flavin mononucleotide (FMN)-containing old yellow enzymes (OYEs) catalyze bioreduction of a broad variety of substrates, including α, β-unsaturated aldehydes, ketones, esters, nitriles, and nitro compounds. 1,4 The increasing studies on discovery and engineering of EREDs, and combining EREDs with chemocatalysis raise the potential for application of EREDs in pharmaceutical synthesis and organic synthesis.…”

“…1,4 The increasing studies on discovery and engineering of EREDs, and combining EREDs with chemocatalysis raise the potential for application of EREDs in pharmaceutical synthesis and organic synthesis. [1][2][5][6][7][8][9][10] The "profen" drugs, such as ibuprofen, flurbiprofen, ketoprofen, and naproxen, which have the 2-arylpropionic acid skeletons, belong to an important and frequently used group of non-steroidal anti-inflammatory drugs (NSAIDs). Although ibuprofen and ketoprofen are often used as racemic mixtures, the (S)-enantiomers of "profens" are the main bioactive enantiomers for cyclooxygenase (COX) inhibition, whereas the (R)-enantiomers are generally not considered as COX inhibitors.…”