Kinetic resolutions of indan derivatives using bacteria

Area of Science:

• Biocatalysis
• Organic Chemistry
• Enzyme Technology

Background:

• Chiral compounds are crucial in pharmaceuticals and fine chemicals.
• Efficient methods for enantioselective synthesis are in high demand.
• Biocatalytic kinetic resolution offers a sustainable approach to chiral compound production.

Purpose of the Study:

• To investigate the use of Corynebacterium ammoniagenes IFO12612 for resolving racemic indan derivatives.
• To develop a scalable biocatalytic method for producing enantiopure (S)-amines and (R)-amides.
• To optimize the kinetic resolution of a specific indan derivative, N-[2-(6-methoxy-indan-1-yl)ethyl]acetamide.

Main Methods:

• Hydrolysis of amide bonds using the enzyme from Corynebacterium ammoniagenes IFO12612.
• Kinetic resolution of racemic N-[2-(6-methoxy-indan-1-yl)ethyl]acetamide.
• Scale-up of the reaction to a 10-g level.
• Analysis of enantiomeric excess (ee) using chiral chromatography.

Main Results:

• Successful resolution of racemic indan derivatives into (S)-amines and (R)-amides.
• Achieved 44% conversion for the kinetic resolution of N-[2-(6-methoxy-indan-1-yl)ethyl]acetamide.
• Obtained (S)-amine 4 ((S)-2-(6-methoxy-indan-1-yl)ethylamine) with >99% enantiomeric excess.
• Isolated the corresponding (R)-amide 1 with 98% enantiomeric excess.

Conclusions:

• Corynebacterium ammoniagenes IFO12612 is an effective biocatalyst for the enantioselective hydrolysis of indan amide derivatives.
• The method provides a scalable and efficient route to high-purity chiral amines and amides.
• This biocatalytic approach holds promise for the industrial production of valuable chiral intermediates.