Chemoenzymatic synthesis of optically active Mugetanol isomers: use of lipases and oxidoreductases in fragrance chemistry

Straightforward synthetic strategies for the preparation of optically active Mugetanol isomers have been developed through different independent chemoenzymatic routes implying the use of either alcohol dehydrogenases in aqueous media or lipases in organic solvents coupled with a catalytic hydrogenation process. Among the alcohol dehydrogenases tested, ADH RS1 showed the best activities in the bioreduction of 4-isopropylacetophenone. The lipase from Pseudomonas cepacia (PSL-C I) reached high activity values in the lipase-catalyzed transesterification of 4-isopropylphenyl)ethanol, while Candida antarctica lipase B showed the best stereopreference in the acetylation of 4-isopropylcyclohexylethanol.

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(+)-1-(S)-(4-Isopropylphenyl)ethanolC11H16OEe >99% (HPLC, Chiralpak IA)[α]D20=+82.2 (c 1.2, CHCl3)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (S)

(+)-1-(R)-(4-Isopropylphenyl)ethyl acetateC13H18O2Ee 98% (HPLC, Chiralpak IA)[α]D20=+78.5 (c 1.2, CH2Cl2)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (R)

(+)-1-(S)-(4-Isopropylcyclohexyl)ethanolC11H22OEe 98% (GC, Chiralsil Dex-CB)De 64% (1H NMR)[α]D20=+8.6 (c 3.3, EtOH)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (S)

(+)-1-(R)-(4-Isopropylcyclohexyl)ethyl acetateC13H24O2Ee >99% (GC, Chiralsil Dex-CB)De 15% (GC, Chiralsil Dex-CB)[α]D20=+1.2 (c 0.66, CH2Cl2)Source of chirality: enzymatic kinetic resolutionAbsolute configuration: (R)