Abstract
Biological target: Menthol is a natural terpenoid with agonist activity at the thermoreceptive, non-selective cation channel, transient receptor potential melastatin type 8 (TRPM8). Present on nerve fibres and skin cells, these channels are activated by a fall in temperature and mediate analgesia. Menthol is also an agonist at GABAA receptors, for which (+)-menthol reveals stereoselectivity.
Therapeutic profile: (−)-Menthol is a household medicament, widely used as a local anaesthetic and analgesic, to reduce itching, as a gastric sedative agent and as a decongestant.
Synthetic highlight: Diastereoselective production of rac-menthol from its aromatic precursor is achieved by site-selective isopropylation and diastereoselective hydrogenation to the all-trans racemate. Enantioselective allylic amine–enamine–imine rearrangement of an acyclic diene-allylic amine, catalyzed by an Rh(I)-(−)-BINAP complex, affords (−)-menthol; the process has been scaled-up to production of 1,000 tons/year.
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Šunjić, V., Parnham, M.J. (2011). (−)-Menthol. In: Signposts to Chiral Drugs. Springer, Basel. https://doi.org/10.1007/978-3-0348-0125-6_9
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DOI: https://doi.org/10.1007/978-3-0348-0125-6_9
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