Simple approach to optically active drimane sesquiterpenes based on enzymatic resolution

Area of Science:

• Biocatalysis and Enzyme Technology
• Organic Chemistry
• Chiral Synthesis

Background:

• Lipases are versatile enzymes used in organic synthesis for selective transformations.
• Chiral compounds are crucial in pharmaceuticals and fine chemicals.
• Stereoselective synthesis remains a key challenge in organic chemistry.

Purpose of the Study:

• To investigate the stereoselective hydrolysis of beta-acyloxy esters using lipases.
• To explore the application of lipases in kinetic resolution for chiral synthesis.
• To confirm the absolute configuration of synthesized chiral intermediates.

Main Methods:

• Enzymatic hydrolysis of racemic beta-acyloxy esters (+/-)-10 and (+/-)-11 using lipase OF-360 (Candida rugosa).
• Kinetic resolution of a diol (+/-)-12 via acylation with isopropenyl acetate using lipase Godo E-4 (Pseudomonas sp.).
• Confirmation of absolute structure through chemical conversion to a gamma-keto nitrile (8aS)-17.

Main Results:

• Lipase OF-360 efficiently hydrolyzed the beta-acyloxy esters, yielding (8aS)-6 in 40% chemical yield and >99% enantiomeric excess (ee).
• Lipase Godo E-4 selectively acylated the diol (+/-)-12, resulting in the recovery of the unchanged (8aR)-12 with 89% ee in 42% yield.
• The absolute configuration of (8aS)-6 was unequivocally confirmed.

Conclusions:

• Lipase OF-360 is effective for the highly enantioselective synthesis of chiral alcohols from beta-acyloxy esters.
• Lipase Godo E-4 can be utilized for the kinetic resolution of diols, yielding enantiomerically enriched alcohols.
• These enzymatic methods offer a viable route for accessing valuable chiral building blocks.