1206901-82-7Relevant academic research and scientific papers
Natural-Product-Derived Transient Receptor Potential Melastatin 8 (TRPM8) Channel Modulators
Legay, Christina M.,Gorobets, Evgueni,Iftinca, Mircea,Ramachandran, Rithwik,Altier, Christophe,Derksen, Darren J.
, p. 2746 - 2749 (2016/06/15)
A library of novel structural hybrids of menthol and cubebol was tested for each derivative's ability to interact with the transient receptor potential subfamily melastatin member 8 (TRPM8) channel. This structure-activity relationship study revealed three potent modulators of the TRPM8 ion channel: a novel agonist (4) with an EC50 value of 11 ± 1 μM, an antagonist (15) with an IC50 value of 2 ± 1 μM, and an allosteric modulator (21) that minimized channel desensitization toward menthol. Each of these novel exocyclic olefin analogues of menthol is readily accessible by synthesis and was tested using Ca2+ assays and electrophysiology.
Stereocontrolled syntheses of (-)-cubebol and (-)-10-epicubebol involving intramolecular cyclopropanation of a-lithiated epoxides
Hodgson, David M.,Salik, Saifullah,Fox, David J.
supporting information; experimental part, p. 2157 - 2168 (2010/06/17)
Figure Presented Formylation of (-)-menthone (11) with LDA and HCO 2CH2CF3 avoids loss of configurational integrity at the isopropyl group, giving hydroxymethylenementhone 12. Lithium 2,2,6,6-tetramethylpiperidideinduced intramolecular cyclopropanation of derived unsaturated terminal epoxide 17 (and chlorohydrin 16), efficiently generates a substituted tricyclo[4.4.0.01.5]decan-4-ol 18, which is used in a concise synthesis of (-)-cubebol (1). In contrast, isopropyl group inversion during formylation of menthone with NaOMe and HCO2Et led, by a similar strategy, to syntheses of 7-epicubebol (33) and (from(+)-menthone) of naturally occurring (-)-10-epicubebol (39), confirming the original structural assignment. Computational studies support the origin of the inversion as being rate-determining formylation of cis-enolate 27 from amixture of rapidly interconverting enolates. In the synthesis of 7-epicubebol (33), allylic tertiary C-H insertion is observed as a significant competing reaction in the intramolecular cyclopropanation of unsaturated terminal epoxide 22.
