A one-pot biocatalytic and organocatalytic cascade delivers high titers of 2-ethyl-2-hexenal from n-butanol

Abstract

Biocatalysis provides facile access to selective chemical transformations and helps satisfy sustainable chemical production criteria. However, the reaction scope of biocatalysts is significantly narrower compared to synthetic chemical transformations. Hybrid...

A Four-Step Biocatalytic and Organocatalytic Cascade for Single-Flask Production of Dinitroalkanes from Alcohols in Aqueous Buffer

“…In previous studies, increasing the initial substate loading has delivered higher titers (17); however, higher substrate loadings would require a proportional increase in nitromethane loadings, which will decrease enzyme performance. An increase in temperature would likely improve the organocatalysed cascade of butyraldehyde to the dinitroalkane while maintaining current nitromethane loadings; however, alcohol oxidase performs optimally at 30°C (17,21). Instead, we next investigated how a sequential reaction one-pot reaction compared to a reaction with all reagents added at the onset.…”

“…In previous work, we successfully combined whole-cell (G. oxidans, K. pastoris) and enzyme-catalysed oxidation (alcohol oxidase (AO)) of aliphatic alcohols with a biocompatible organocatalysed aldol condensation to furnish industrially relevant α,βunsaturated aldehydes (17,18). Building off of this work, we sought to expand upon the products accessible through the merger of biocatalysis and organocatalysis.…”

One-pot cascade reactions for the synthesis of dinitroalkanes in aqueous buffer

“…In previous work, we successfully combined whole-cell (G. oxidans, K. pastoris) and enzyme-catalysed oxidation (alcohol oxidase (AO)) of aliphatic alcohols with a biocompatible organocatalysed aldol condensation to furnish industrially relevant α,β-unsaturated aldehydes. 18,19 Building off of this work, we sought to expand upon the products accessible through the merger of biocatalysis and organocatalysis. Previous efforts to combine organocatalysis and biocatalysis include the synthesis of optically active diols, 20 aminolactones, 21 indole derivatives, 22 and aldol condensation products, 23 among others.…”

“…Because each amino acid catalyst performed similarly across the three amino acids tested, we chose lysine because of our previous work using lysine as a biocompatible organocatalyst. 18,19 To further drive the reaction toward the dinitroalkane, we increased the relative stoichiometry of nitromethane (Fig. 4).…”

“…An increase in temperature would likely improve the organocatalysed cascade of butyraldehyde to the dinitroalkane while maintaining current nitromethane loadings; however, alcohol oxidase performs optimally at 30 °C. 18,31 Because we do not see any overoxidation to the carboxylic acid in our experimental conditions, we next investigated how a sequential reaction one-pot reaction compared to a reaction with all reagents added at the onset. We anticipated that this may help alleviate incompatibilities between the organocatalytic cascade and bio-enzymatic oxidation step.…”