Stereochemistry of terpene derivatives. Part 6: Chemoenzymatic synthesis of chiral bicyclo[3.1.0]hexane derivatives with olfactory properties

Starting from (+)-3-carene 1, several chiral fragrant compounds with the bicyclo[3.1.0]hexane system were synthesized. These compounds were used as substrates for the biotransformation with lipases as biocatalysts. Pure diastereoisomers were obtained and their absolute configuration was confirmed by X-ray crystallography. The olfactory properties of new compounds were determined.

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(+)-(1R)-1-[(1S,5R)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl)]ethyl acetateC12H18O2Ee = 100%[α]D26=+180.0 (c 1.0, CHCl3)Source of chirality: enzymatic transesterificationAbsolute configuration: (1R,1′S,5′R)

(+)-(1R)-1-[(1S,5R)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl)]ethanolC10H16OEe = 100%[α]D29=+69.0 (c 1.0, CHCl3)Source of chirality: (+)-(1R)-1-[(1S,5R)-6,6-dimethyl-bicyclo[3.1.0]hex-2-en-2-yl)]ethyl acetateAbsolute configuration: (1R,1′S,5′R)

(+)-(1R)-1-[(1S,5R)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl)ethyl p-nitrobenzoateC17H19NO4Ee = 100%[α]D28=+15.2 (c 1.0, CHCl3)Source of chirality: (+)-(1R)-1-[(1S,5R)-6,6-dimethyl-bicyclo[3.1.0]hex-2-en-2-yl)]ethanolAbsolute configuration: (1R,1′S,5′R)

(+)-(1S)-1-[(1S,5R)-6,6-Dimethylbicyclo[3.1.0]hex-2-en-2-yl)]ethanolC10H16OEe = 78%[α]D29=+12.0 (c 1.0, CHCl3)Source of chirality: enzymatic transesterificationAbsolute configuration: (1S,1′S,5′R)