Diastereoselective synthesis of optically active (2 R,5 R)-hexanediol

Area of Science:

• Biocatalysis and enzyme technology
• Organic chemistry
• Microbial fermentation

Background:

• Chiral diols are valuable building blocks in organic synthesis.
• Stereoselective reduction of ketones is crucial for producing enantiomerically pure compounds.
• Biocatalytic methods offer sustainable alternatives to traditional chemical synthesis.

Purpose of the Study:

• To investigate the diastereoselective reduction of diketones using Lactobacillus kefir DSM 20587.
• To optimize reaction conditions for maximizing yield and stereoselectivity.
• To evaluate the system's performance in fed-batch fermentation for potential industrial application.

Main Methods:

• Enzymatic reduction of (2,5)-hexanedione using Lactobacillus kefir DSM 20587.
• Optimization of pH, temperature, substrate-to-cosubstrate ratio.
• Fed-batch cultivation experiments to assess scalability.
• Analysis of product yield, enantiomeric excess (ee), and diastereomeric excess (de) using chiral chromatography.

Main Results:

• Highly diastereoselective reduction of both oxo-functions in (2,5)-hexanedione was achieved.
• (2 R,5 R)-Hexanediol was produced in quantitative yields with >99% ee and >99% de.
• Optimal conditions identified as pH 6, 30°C, and equimolar substrate/cosubstrate.
• Successful demonstration of the system in fed-batch experiments, determining optimal biomass concentration for maximal yield and selectivity.

Conclusions:

• Lactobacillus kefir DSM 20587 is a highly effective biocatalyst for the stereoselective synthesis of (2 R,5 R)-hexanediol from diketones.
• The optimized process offers a sustainable and efficient route to enantiomerically pure chiral diols.
• The demonstrated fed-batch capability highlights the potential for large-scale production.