2216-54-8Relevant academic research and scientific papers
Structural and in Vitro Functional Characterization of a Menthyl TRPM8 Antagonist Indicates Species-Dependent Regulation
Journigan, V. Blair,Alarcón-Alarcón, David,Feng, Zhiwei,Wang, Yuanqiang,Liang, Tianjian,Dawley, Denise C.,Amin, A. R. M. Ruhul,Montano, Camila,Van Horn, Wade D.,Xie, Xiang-Qun,Ferrer-Montiel, Antonio,Fernández-Carvajal, Asia
, p. 758 - 767 (2021/05/04)
TRPM8 antagonists derived from its cognate ligand, (-)-menthol, are underrepresented. We determine the absolute stereochemistry of a well-known TRPM8 antagonist, (-)-menthyl 1, using VCD and 2D NMR. We explore 1 for its antagonist effects of the human TRPM8 (hTRPM8) orthologue to uncover species-dependent inhibition versus rat channels. (-)-Menthyl 1 inhibits menthol- and icilin-evoked Ca2+ responses at hTRPM8 with IC50 values of 805 ± 200 nM and 1.8 ± 0.6 μM, respectively, while more potently inhibiting agonist responses at the rat orthologue (rTRPM8 IC50 (menthol) = 117 ± 18 nM, IC50 (icilin) = 521 ± 20 nM). Whole-cell patch-clamp recordings of hTRPM8 confirm the 1 inhibition of menthol-stimulated currents, with an IC50 of 700 ± 200 nM. We demonstrate that 1 possesses ≥400-fold selectivity for hTRPM8 versus hTRPA1/hTRPV1. (-)-menthyl 1 can be used as a novel chemical tool to study hTRPM8 pharmacology and differences in species commonly used in drug discovery.
Menthylamine synthesis via gold-catalyzed hydrogenation of menthone oxime
Demidova, Yu. S.,Mozhaitsev, E. S.,Murzin, D. Yu.,Nefedov, A. A.,Salakhutdinov, N. F.,Saraev, A. A.,Simakov, A.,Simakova, I. L.,Suslov, E. V.,Volcho, K. P.
, (2020/09/03)
In the current work gold nanoparticles supported on oxides (MgO, Al2O3, ZrO2, TiO2) were used for menthylamine synthesis via menthone oxime hydrogenation. An increase of the gold nanoparticles size and application of metal oxides with a strong basic character such as magnesia favored deoximation to menthone. Au/Al2O3 catalyst with the gold nanoparticles size of 2.0 nm afforded high catalytic activity and selectivity to menthylamine. The reaction kinetics including stereoselectivity to the reaction products and recyclability of the catalyst was studied using Au/Al2O3 in the temperature range 90?110 °C under hydrogen pressure of 5.5–7.5 bar. The catalytic behavior was influenced by the solvent nature, with higher selectivity to desired amine achieved using methanol. The reaction rate was pressure independent, while has first order with respect to menthone oxime concentration. Stereoselectivity to menthylamines and menthones was independent on the reaction temperature and the hydrogen pressure.
Efficient resolution of menthylamine with inexpensive (r,r)-tartaric acid by dielectrically controlled resolution (DCR)
Schmitt, Magdalena,Schollmeyer, Dieter,Waldvogel, Siegfried R.
, p. 1007 - 1012 (2014/03/21)
A practical procedure for the resolution of menthylamine 2 with (R,R)-tartaric acid [(R,R)-3] as resolving agent is presented. Variation of the solvent system allows both enantiomers of 2 to be selectively crystallized. Performing the resolution in methanol containing 6 % water leads to (-)-2·(R,R)-3·MeOH. The other, less-soluble diastereomeric salt is obtained by applying a solvent system consisting of methanol with 19 % water with a yield of 14 %. Subsequent basic workup with aqueous sodium hydroxide gave the free menthylamine compounds. Further workup of the mother liquors and an additional recrystallization step allowed the (-)-2·(R,R)-3·MeOH salt to be obtained in an overall yield of 22 %; the other salt (+)-2·(R,R)-3·MeOH·H2O was obtained in 23 % yield. This is another important example of the dielectrically controlled resolution of an interesting amine by using inexpensive (R,R)-tartaric acid as resolving agent. With the same inexpensive resolving agent, (R,R)-tartaric acid, both antipodes of menthylamine can be selectively crystallized as diastereomeric salts. The concentration of water determines which salt is formed. In a few simple resolution steps, good yields and high enantiomeric excess can be achieved. Copyright
Efficient and stereodivergent electrochemical synthesis of optically pure menthylamines
Kulisch, Joern,Nieger, Martin,Stecker, Florian,Fischer, Andreas,Waldvogel, Siegfried R.
, p. 5564 - 5567 (2011/07/30)
The cathode directs the way to the epimeric menthylamines. The reduction of menthone oxime on a Hg cathode generates (-)-menthylamine as the major product, whereas a Pb cathode gives access to (+)-neomenthylamine (see scheme). Insitu decoration of the Pb cathode by small amounts of additives results in clean and quantitative conversions. Furthermore, Pb corrosion is completely prevented in this practical method. Copyright
Asymmetric hydroamination catalyzed by in situ generated chiral amidate and ureate complexes of zirconium - Probing the role of the tether in ligand design
Payne, Philippa R.,Bexrud, Jason A.,Leitch, David C.,Schafer, Laurel L.
experimental part, p. 1222 - 1229 (2012/02/06)
Simple chiral proligands have been synthesized from inexpensive chiral starting materials. These amidate and ureate ligands support zirconium complexes that successfully catalyze intramolecular hydroamination with up to 26% ee. Several elements necessary for successful ligand design are highlighted and discussed. In particular, the strict control of metal geometry through multidentate tethered ligands is determined to be an essential aspect of future ligand development.
Practical synthesis of optically pure menthylamines starting from racemic neomenthol
Welschoff, Nina,Waldvogel, Siegfried R.
experimental part, p. 3596 - 3601 (2010/12/19)
A reliable and scalable route to racemic and highly enantiomerically enriched menthylamines exploits the technical product rac-neomenthol as the starting material. The elaborated protocol is based on nucleophilic substitution of the hydroxy moiety by azide. Subsequent reduction and resolution with tartaric acid provides the desired optically enriched menthylamines.
ELECTROCHEMICAL PRODUCTION OF STERICALLY HINDERED AMINES
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Page/Page column 4, (2009/10/18)
The present invention relates to a process for preparing an amine, which comprises the step cathodic reduction of a corresponding oxime derivative of the general formula (I) where R is C1-6-alkyl or C2-6-alkenyl which is optionally substituted by one or more substituents selected independently from the group consisting of phenyl, O—C1-6-alkyl, NH—C1-6-alkyl, N(C1-6-alkyl)2, OH and NH2;R1 is H; C1-6-alkyl or C(O)—C1-6-alkyl and A is a 5-, 6- or 7-membered hydrocarbon ring which is saturated or has a double bond and in which at least one CH2 group may, if appropriate, be replaced by —O—, —S— —NH—, —N═ or —N(C1-6-alkyl)- and which may optionally be substituted by one or more further substituents selected independently from the group consisting of phenyl, C1-6-alkyl, O—C1-6-alkyl, NH—C1-6-alkyl, N(C1-6-alkyl)2, OH and NH2; wherein, based on the ring carbon bearing the substituent R, the oxime derivative has an excess of the R or S form of at least 10%.
Synthesis and Characterization of Enantiomerically Pure Menthylamines and Their Isocyanates
Schopohl, Matthias C.,Bergander, Klaus,Kataeva, Olga,Froehlich, Roland,Waldvogel, Siegfried R.
, p. 2689 - 2694 (2007/10/03)
A synthetic protocol for optically pure (-)-menthylamine, (-)-8-methylmenthylamine, and the novel (-)-8-phenylmenthylamine is presented including a detailed characterization of these compounds and their isocyanates.
CHIRAL LIGANDS CONTAINING HETEROATOMS. (S)-PROLINE AND (1R)-MENTHYLAMINE AS PRECURSORS OF MODIFIED LITHIUM ALUMINIUM HYDRIDE REAGENTS
Falorni, Massimo,Lardicci, Luciano,Giacomelli, Giampaolo
, p. 73 - 76 (2007/10/02)
A procedure for the preparation of (S)-2-pyrrolidine and of (S)-2-pyrrolidyl-N-oxalyl diamide from (S)-proline and (1R)-menthylamine is described.The results have shown the absence of racemization phenomena in the sequences adopted.The ligands obtained were used for chelating LiAlH4 in enantioselective reductions of phenyl ketones.
