Alcohol Oxidase-Imine Reductase Cascade for One-Pot Chiral Amine Synthesis

Area of Science:

• Biocatalysis
• Organic Chemistry
• Enzymology

Background:

• Chiral amines are crucial building blocks in pharmaceuticals and fine chemicals.
• Efficient and selective synthesis of enantioenriched amines remains a significant challenge.
• Current methods often involve multiple steps, limiting efficiency and increasing waste.

Purpose of the Study:

• To develop a novel one-pot biocatalytic cascade for synthesizing enantioenriched secondary amines.
• To utilize a tandem enzymatic system combining oxidation and conjugate reduction-reductive amination (CR-RA).
• To explore the substrate scope and efficiency of this novel biocatalytic approach.

Main Methods:

• A one-pot reaction sequence involving oxidation followed by conjugate reduction-reductive amination (CR-RA).
• Enzymatic catalysis using cholesterol oxidase (ShCO) for oxidation and ene-imine reductase (EneIRED) for CR-RA.
• Screening of reaction conditions to optimize yield and enantioselectivity.

Main Results:

• Successful conversion of allylic alcohols to enantioenriched secondary amines in a single pot.
• The cascade reaction proceeds under mild conditions.
• A broad substrate scope was demonstrated, with varying selectivity depending on the substrate.
• The one-pot cascade generally outperformed the stepwise approach in efficiency.

Conclusions:

• The developed one-pot biocatalytic cascade offers an efficient and streamlined method for chiral amine synthesis.
• Tandem enzymatic systems provide advantages over stepwise methods for complex transformations.
• This approach holds promise for sustainable and cost-effective production of valuable chiral amines.