Enzymatic resolution of racemic secondary cyclic allylic alcohols

The resolutions of five racemic cyclic alcohols: 6,6-dimethylcyclohex-2-en-1-ol (±)-5, 4,4-dimethylcyclohex-2-en-1-ol (±)-7, 5,5-dimethylcyclohex-2-en-1-ol (±)-11 and isomeric trans-(±)-13 and cis-piperitols (±)-14 are presented. They were resolved by enzymatic esterification with vinyl esters or by enzymatic hydrolysis of their racemic esters in phosphate buffer. The following lipases were used as biocatalysts: Novozyme 435 (Candida antarctica), Amano PS (Burkholderia cepacia) and lipase from Candida cylindracea. All isomers of alcohols were obtained with at least 96% ee.

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(−)-(R)-6,6-Dimethylcyclohex-2-en-1-olC8H14OEe = 98%[α]D29=-126.9 (c 0.81, CHCl3)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (R)

(−)-(R)-6,6-Dimethylcyclohex-2-en-1-yl acetateC10H16O2Ee = 98%[α]D24=-178.6 (c 0.90, CHCl3)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (R)

(+)-(R)-4,4-Dimethylcyclohex-2-en-1-olC8H14OEe = 98%[α]D28=+113.2 (c 0.71, CHCl3)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (R)

(−)-(S)-4,4-Dimethylcyclohex-2-en-1-yl acetateC10H16O2Ee = 96%[α]D23=-155.9 (c 0.97, CHCl3)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (S)

(−)-(S)-5,5-Dimethylcyclohex-2-en-1-olC8H14OEe = 98%[α]D28=-59.8 (c 0.62, CHCl3)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (S)

(−)-(S)-5,5-Dimethylcyclohex-2-en-1-yl acetateC10H16O2Ee = 98%[α]D24=-92.5 (c 1.08, CHCl3)Source of chirality: chemo-enzymatic synthesisAbsolute configuration: (S)

(+)-(3R,4R)-trans-PiperitolC10H18OEe = 98%[α]D27=+35.4 (c 1.40, C2H5OH)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (3R,4R)

(−)-(3S,4S)-trans-Piperityl propionateC13H22O2Ee = 98%[α]D24=-128.1 (c 1.53, CHCl3)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (3S,4S)

(+)-(3R,4S)-cis-PiperitolC10H18OEe = 99%[α]D26=+192.9 (c 2.06, C2H5OH)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (3R,4S)

(−)-(3S,4R)-cis-Piperityl propionateC13H22O2Ee = 97%[α]D27=-288.6 (c 1.60, CHCl3)Source of chirality: enzyme-mediated kinetic resolutionAbsolute configuration: (3S,4R)

(−)-(R)-Ethyl (5′,5′-dimethylcyclohex-2′-en-1′-yl)acetateC12H20O2Ee = 98%[α]D23=-33.5 (c 0.71, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(−)-(R)-2-(5′,5′-Dimethylocyclohex-2′-en-1′-yl)ethanolC10H18OEe = 98%[α]D22=-51.7 (c 0.90, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(+)-2-((R)-5,5-Dimethylcyclohex-2-en-1-yl)ethyl (S)-mandalateC18H24O3Ee = 98%[α]D29=+33.6 (c 0.75, CH3OH)Source of chirality: asymmetric synthesisAbsolute configuration: (2R,1′S)