biostudies-literatureTassano EAustrian Science Fund FWF2742-2751https://www.ebi.ac.uk/biostudies/studies/S-EPMC6099231biostudies-literatureUnknown360(14)The biocatalytic asymmetric disproportionation of aldehydes catalyzed by horse liver alcohol dehydrogenase (HLADH) was assessed in detail on a series of racemic 2-arylpropanals. Statistical optimization by means of design of experiments (DoE) allowed the identification of critical interdependencies between several reaction parameters and revealed a specific experimental window for reaching an 'optimal compromise' in the reaction outcome. The biocatalytic system could be applied to a variety of 2-arylpropanals and granted access in a redox-neutral manner to enantioenriched (<i>S</i>)-profens and profenols following a parallel interconnected dynamic asymmetric transformation (PIDAT). The reaction can be performed in aqueous buffer at ambient conditions, does not rely on a sacrificial co-substrate, and requires only catalytic amounts of cofactor and a single enzyme. The high atom-efficiency was exemplified by the conversion of 75 mM of <i>rac</i>-2-phenylpropanal with 0.03 mol% of HLADH in the presence of ∼0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD⁺), yielding 28.1 mM of (<i>S</i>)-2-phenylpropanol in 96% <i>ee</i> and 26.5 mM of (<i>S</i>)-2-phenylpropionic acid in 89% <i>ee</i>, in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg-scale, with intact enantiopurities.Advanced synthesis & catalysisBiocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α-Substituted Aldehydes: Atom-Efficient Access to Enantiopure (<i>S</i>)-Profens and Profenols.PMC6099231P 30519P30519Tassano EHall MFaber KfalseBiocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α-Substituted Aldehydes: Atom-Efficient Access to Enantiopure (<i>S</i>)-Profens and Profenols.The biocatalytic asymmetric disproportionation of aldehydes catalyzed by horse liver alcohol dehydrogenase (HLADH) was assessed in detail on a series of racemic 2-arylpropanals. Statistical optimization by means of design of experiments (DoE) allowed the identification of critical interdependencies between several reaction parameters and revealed a specific experimental window for reaching an 'optimal compromise' in the reaction outcome. The biocatalytic system could be applied to a variety of 2-arylpropanals and granted access in a redox-neutral manner to enantioenriched (<i>S</i>)-profens and profenols following a parallel interconnected dynamic asymmetric transformation (PIDAT). The reaction can be performed in aqueous buffer at ambient conditions, does not rely on a sacrificial co-substrate, and requires only catalytic amounts of cofactor and a single enzyme. The high atom-efficiency was exemplified by the conversion of 75 mM of <i>rac</i>-2-phenylpropanal with 0.03 mol% of HLADH in the presence of ∼0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD⁺), yielding 28.1 mM of (<i>S</i>)-2-phenylpropanol in 96% <i>ee</i> and 26.5 mM of (<i>S</i>)-2-phenylpropionic acid in 89% <i>ee</i>, in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg-scale, with intact enantiopurities.2018-01-01T00:00:00Z2018 Jul2025-04-19T06:29:48.013Z2019-03-26T23:52:48ZS-EPMC60992313014763910.1002/adsc.201800541