Biocatalytic Approaches to the Synthesis of Enantiomerically Pure Chiral Amines

Physiology, Biochemistry, and Applications of F420- and Fo-Dependent Redox Reactions

“…As F 420 H 2 -dependent reductases deliver hydrides from the cofactor, it is likely that they will provide access to cis-hydrogenation of enones for biocatalytic processes (including in vivo). Asymmetric imine reduction by enzymes is a promising area for development (483), not least because of the prominence of chiral amines in modern synthetic chemistry: ϳ40% of pharmaceuticals and ϳ20% of agrochemicals contain at least one chiral amine (484). However, the toolbox of enzymes available for use in such applications is still small and incomplete; there are few enzymes that will reduce a prochiral imine in a linear molecule, for example (483).…”

Stereoselective Access to 1-[2-Bromo(het)aryloxy]propan-2-amines Using Transaminases and Lipases; Development of a Chemoenzymatic Strategy Toward a Levofloxacin Precursor

“…9 Substrates 1a-g were alkylated using an equimolecular amount of chloroacetone (2) in the presence of 2 equiv of potassium carbonate and catalytic amounts of potassium iodide in refluxing acetone, obtaining after 2 h the ketones 3a-g in high to quantitative yields. Prochiral ketones 3a-g served as substrates for biotransamination reactions, but also as starting materials for the synthesis of the racemic amines through reductive amination using 2 equiv of sodium cyanoborohydride in combination with a large of excess of ammonium acetate in methanol.…”

“…1 Remarkably, the use of biotransformations provides nowadays a plethora of possibilities for the design of stereoselective routes toward enantiopure amines and their derivatives. 2 Optically active 1-aryloxy-propan-2-amines (Scheme 1, R 2 = NH2) are particularly attractive nitrogenous compounds, the absolute configuration of their chiral center having a remarkable importance in their biological profiles. 3 From this family, [1-(2,6-dimethylphenoxy)propan-2-amine, also called as mexiletine, has attracted great attention for clinical purposes due to its properties as antiarrhythmic agent.…”

Fluorescence‐Based Kinetic Assay for High‐Throughput Discovery and Engineering of Stereoselective ω‐Transaminases

“…[9] Although knowledge about their natural functions and substratesi ss till sparse,m any have proven useful for biotechnological applications, such as those includedi nT able 1( entries 1-8). [1][2][3] The assumedw ide substrate diversity is matched by structural variations in the substrate-binding tunnels of wtransaminases,w hich are interesting for the selective binding and conversion of various unnatural ketone acceptors towards the development of future applications in the synthesiso fabroad diversity of chiral amines.T herefore,s earching for yet unidentified wtransaminases in databases for novel specificities is still ak ey topic in the w-transaminase research arena. Taurine-pyruvate transaminase is classifieda s am ember of subclade 6a among w-transaminases, which catalyzes transamination between taurine and pyruvate in several microorganisms.…”

“…[1,2] Recently, w-transaminases have enjoyed ap articularf ocus for development because the enzymes in this family offer ag reen route for the reductive amination of prochiral ketones to produce (R)-and (S)-amines in high optical purity and 100% yield. [3] Ar ecent informative example is the engineering of an (R)-selective w-transaminase for the industrial production of sitagliptin, [4] an oral anti-diabetic drug, as ar eplacement for the rhodiumbased,h igh-pressure chemical asymmetric hydrogenation process that suffered from insufficient levels of enantioselectivity and chemical purity.…”