Lipase-catalyzed kinetic resolution on solid-phase via a "capture and release" strategy

Area of Science:

• Organic Chemistry
• Biocatalysis
• Enzyme Technology

Background:

• Lipase-catalyzed kinetic resolution is crucial for chiral compound synthesis.
• The enantioselectivity of lipases can vary significantly between solution-phase and solid-supported reactions.
• 3-phenylbutyric acid is a valuable chiral building block.

Purpose of the Study:

• To investigate the lipase-catalyzed kinetic resolution of racemic 3-phenylbutyric acid using a novel solid-supported method.
• To compare the enantioselectivity of the solid-supported system with established solution-phase reactions.
• To optimize the reaction conditions for improved yield and enantiomeric excess.

Main Methods:

• Kinetic resolution of (R/S)-3-phenylbutyric acid using immobilized cyclohexane-1,3-dione (CHD) on a solid support.
• Enzymatic acylation catalyzed by lipase.
• Cleavage of the product from the solid support.
• Analysis of enantiomeric excess (ee) using chiral chromatography.
• Optimization of reaction conditions, including resin loading and hydrolysis steps.

Main Results:

• The solid-supported method predominantly yielded the (R)-enantiomer of 3-phenylbutyric acid with high enantiomeric excess (>99%).
• This outcome contrasted with solution-phase hydrolysis using Chromobacterium viscosum lipase, which favors the (S)-enantiomer.
• The yield of the desired (R)-acyl group was enhanced by employing triple acylation of the resin.
• NaOH hydrolysis effectively released the (R)-acyl group from the resin.

Conclusions:

• Solid-supported enzymatic resolution can lead to reversed enantioselectivity compared to solution-phase methods.
• The choice of support and reaction phase significantly impacts lipase enantioselectivity.
• The described method offers a promising route for the efficient synthesis of (R)-3-phenylbutyric acid.