An efficient benchtop system for multigram-scale kinetic resolutions using aldolase antibodies

Area of Science:

• Biocatalysis
• Organic Chemistry
• Enzyme Engineering

Background:

• Kinetic resolution is crucial for obtaining enantiomerically pure compounds.
• Aldolase antibodies offer a biocatalytic route for aldol addition reactions.
• Developing scalable and reusable catalytic systems is a key challenge in synthetic chemistry.

Purpose of the Study:

• To describe the preparative scale kinetic resolution of racemic aldols using specific aldolase antibodies.
• To establish a biphasic solvent system for efficient catalyst reuse.
• To demonstrate the accessibility of both aldol product enantiomers through enantioselective kinetic resolution.

Main Methods:

• Kinetic resolution of racemic aldols 1-4 using aldolase antibodies 38C2 and 84G3.
• Employment of a biphasic aqueous/organic solvent system.
• Scalable reactions ranging from milligrams to grams.

Main Results:

• Successful kinetic resolution of racemic aldols was achieved using aldolase antibodies.
• The biphasic system facilitated the reuse of the antibody catalyst.
• Antibodies 38C2 and 84G3, exhibiting opposite enantioselectivities, allowed access to both enantiomers of the aldol products.
• Catalyst loading ranged from 0.0086 to 0.12 mol% antibody binding sites.

Conclusions:

• Aldolase antibodies are effective catalysts for the preparative scale kinetic resolution of racemic aldols.
• The developed biphasic system enhances the sustainability and efficiency of the biocatalytic process.
• This methodology provides a versatile approach for accessing enantiomerically pure aldol products.