title: Hemisynthesis of dihydroumbellulols from umbellulone: new cooling compounds.
abstract: Although menthol is a common ingredient used in food products, other molecules also evoke coolness through stimulation of the somatosensory system. To discover new molecules having cooling properties, we virtually screened the chemical structures of terpenes and sesquiterpenes to find structures that are similar to (-)-menthol. We realized that dihydroumbellulols could be good candidates. Although their occurrence was reported in Hyptis pectinata Poit, we were unable to obtain these molecules from the plant or to prove their natural occurrence. Therefore, we extracted (-)-(R)-umbellulone from Umbellularia californica Nutt. The (-)-(R)-umbellulone was reduced to prepare (1R,2R/S)-1-isopropyl-4-methylbicyclo[3.1.0]hex-3-en-2-ol, (1R,4R/S)-1-isopropyl-4-methylbicyclo[3.1.0]hexan-2-one, and (1R,2RS,4RS)-1-isopropyl-4-methylbicyclo[3.1.0]hexan-2-ols, named dihydroumbellulols. Sensory analysis suggested that (1R,2R,4S)-dihydroumbellulol has a pleasant, trigeminal cooling effect, about 2-3 times less cooling than (-)-menthol, with a weak odor slightly reminiscent of eucalyptol. In addition, a previously unreported compound was discovered, (-)-(1R)-1-isopropyl-4-methylenebicyclo[3.1.0]hexan-2-one.
authors.affiliation: Corporate R&D Division, Firmenich SA, PO Box 239, CH-1211 Geneva 8, Switzerland. christian.starkenmann@firmenich.com
authors.forename: Christian
authors.initials: C
authors.lastname: Starkenmann
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cayeux
authors.forename: Robert
authors.initials: R
authors.lastname: Brauchli
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mayenzet
mesh_terms: D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003511:Cyclohexanols / Q000138:chemical synthesis* / Q000737:chemistry; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000737:chemistry; D005421:Flavoring Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D039821:Monoterpenes; D010936:Plant Extracts / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D027422:Umbellularia / Q000737:chemistry
chemical_list: C557950:1-isopropyl-4-methylbicyclo(3.1.0)hex-3-en-2-ol; D001643:Bridged Bicyclo Compounds; D003511:Cyclohexanols; D003512:Cyclohexanones; D005421:Flavoring Agents; D039821:Monoterpenes; D010936:Plant Extracts; C557948:(1R,5S)-4-methyl-1-propan-2-ylbicyclo(3.1.0)hex-3-en-2-one