Synthesis of optically active dihydrocarveol via a stepwise or one-pot enzymatic reduction of (R)- and (S)-carvone

A recombinant enoate reductase LacER from Lactobacillus casei catalyzed the reduction of (R)-carvone and (S)-carvone to give (2R,5R)-dihydrocarvone and (2R,5S)-dihydrocarvone with 99% and 86% de, respectively, which were further reduced to dihydrocarveols by a carbonyl reductase from Sporobolomyces salmonicolorSSCR or Candida magnoliaCMCR. For (R)-carvone, (1S,2R,5R)-dihydrocarveol was produced as the sole product with >99% conversion, while (1S,2R,5S)-dihydrocarveol was obtained as the major product, but with a lower de when (S)-carvone was used as the substrate. The one-pot reduction was performed at a 0.1 M substrate concentration, indicating that it might provide an effective synthetic route to this type of chiral compound.

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(2R,5R)-DihydrocarvoneC10H16Ode: 99%[α]D20=+12.4 (c 3.3, CH3CH2OH)Source of chirality: enzymatic reductionConfiguration: (2R,5R)

(1S,2R,5R)-DihydrocarveolC10H18Ode: 99%[α]D20=+17.3 (c 2.4, CH3CH2OH).Source of chirality: enzymatic reductionConfiguration: (1S,2R,5R)

(2R,5S)-DihydrocarvoneC10H16Ode: 86%[α]D20=-17.3 (c 3.3, CH3CH2OH).Source of chirality: enzymatic reductionConfiguration: (2R,5S)