Enzymatic synthesis of (R) and (S) 1-deuterohexanol

Area of Science:

• Biocatalysis
• Organic Synthesis
• Materials Science

Background:

• Chiral molecules are crucial building blocks in advanced materials like liquid crystals.
• Enzymatic synthesis offers stereoselective routes to valuable chiral compounds.
• 1-deuterohexanol is a key intermediate for chiral poly isocyanated liquid crystals.

Purpose of the Study:

• To develop practical enzymatic procedures for synthesizing (R) and (S) 1-deuterohexanol.
• To optimize reaction conditions for improved yields and enzyme stability.
• To explore the use of immobilized enzymes for efficient production.

Main Methods:

• Enzymatic reduction of hexanal using alcohol dehydrogenases (from horse liver and Pseudomonas) with deuterated NAD (NADD).
• In situ regeneration of the deuterated cofactor via alcohol dehydrogenase-catalyzed oxidation of deuterated alcohols (ethanol-d6 or 2-propanol-d8).
• Chemical synthesis of 1-deuterohexanal followed by enzymatic reduction.
• Application of biphasic systems and immobilized enzymes (on PAN or XAD resin) in anhydrous organic solvents.

Main Results:

• Achieved 50% yield of (R)-1-deuterohexanol and 89% yield of (S)-1-deuterohexanol via hexanal reduction.
• Demonstrated successful cofactor regeneration using deuterated ethanol or 2-propanol.
• Showcased significantly increased reaction yields using biphasic systems or immobilized enzymes.
• Enhanced stability of horse liver alcohol dehydrogenase through immobilization.

Conclusions:

• Practical and efficient enzymatic methods for synthesizing enantiomerically enriched 1-deuterohexanol were established.
• Enzyme immobilization and specific reaction conditions are key to improving yield and stability.
• This work provides a valuable route for producing chiral building blocks for advanced materials.