Chemistry:Mesylate
In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (CH
3SO
3H). In salts, the mesylate is present as the CH
3SO−
3 anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the group or anion, the spelling used is sometimes mesilate (as in imatinib mesilate, the mesylate salt of imatinib).[1]
Mesylate esters are a group of organic compounds that share a common functional group with the general structure CH
3SO
2O–R, abbreviated MsO–R, where R is an organic substituent. Mesylate is considered a leaving group in nucleophilic substitution reactions.[2]
Preparation
Mesylate esters are generally prepared by treating an alcohol and methanesulfonyl chloride in the presence of a base, such as triethylamine.[3]
Mesyl
Related to mesylate is the mesyl (Ms) or methanesulfonyl (CH
3SO
2) functional group. The shortened term itself was coined by Helferich et al. in 1938 similarly to tosyl adopted earlier.[4] Methanesulfonyl chloride is often referred to as mesyl chloride.
Whereas mesylates are often hydrolytically labile, mesyl groups, when attached to nitrogen, are resistant to hydrolysis.[5] This functional group appears in a variety of medications, particularly cardiac (antiarrhythmic) drugs, as a sulfonamide moiety. Examples include sotalol, ibutilide, sematilide, dronedarone, dofetilide, E-4031, and bitopertin.
Pharmaceutical preparations
Mesylate salts are often used in preparing the dosage forms of basic drugs. Mesylate salts often yield a higher solubility, and may also excel in other pharmaceutically-relevant factors such as hygroscopicity, clean polymorphic profile, particle size, and flow properties.[6][7]
Natural occurrence
Ice core samples from a single spot in Antarctica were found to have tiny inclusions of magnesium methanesulfonate dodecahydrate. This natural phase is recognized as the mineral ernstburkeite. It is extremely rare.[8][9]
See also
- Tosylate
- Triflate, the fluorinated analog of mesylate.
References
- ↑ International Nonproprietary Names Modified (Report). World Health Organization. February 2006. INN Working Document 05.167/3. https://www.who.int/medicines/services/inn/INNMreview%20paperWkDoc167_Feb06_3_.pdf. Retrieved 5 December 2008.
- ↑ Smith, Michael B.; March, Jerry (2007). March's Advanced Organic Chemistry (6th ed.). John Wiley & Sons. p. 497. ISBN 978-0-471-72091-1.
- ↑ Rick L. Danheiser; Yeun-Min Tsai; David M. Fink (1966). "A General Method for the Synthesis of Allenylsilanes: 1-Methyl-1-(trimethylsilyl)allene". Organic Syntheses. doi:10.15227/orgsyn.066.0001. (a procedure illustrating the use of mesylates).
- ↑ Helferich, Burckhardt; Gnüchtel, Alfred (1938-04-06). "Ester der Methansulfonsäure in der Zuckergruppe" (in de). Berichte der Deutschen Chemischen Gesellschaft (A and B Series) 71 (4): 712–718. doi:10.1002/cber.19380710403. ISSN 0365-9488. https://onlinelibrary.wiley.com/doi/10.1002/cber.19380710403.
- ↑ Vaillancourt, Valerie; Cudahy, Michele M.; Kreilein, Matthew M.; Jacobs, Danielle L. (2007-09-17). "Methanesulfonyl Chloride". Encyclopedia of Reagents for Organic Synthesis. Chichester, UK: John Wiley & Sons, Ltd. doi:10.1002/047084289x.rm070.pub2. ISBN 978-0-471-93623-7. https://onlinelibrary.wiley.com/doi/10.1002/047084289X.rm070.pub2.
- ↑ "Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations". Molecules 23 (7): 1719. July 2018. doi:10.3390/molecules23071719. PMID 30011904.
- ↑ "The utility of sulfonate salts in drug development". J Pharm Sci 99 (7): 2948–61. July 2010. doi:10.1002/jps.22058. PMID 20112423.
- ↑ Güner, Fatma Elif Genceli; Sakurai, Toshimitsu; Hondoh, Takeo (2013). "Ernstburkeite, Mg(CH3SO3)2·12H2O, a new mineral from Antarctica". European Journal of Mineralogy 25 (1): 78–83. doi:10.1127/0935-1221/2013/0025-2257. Bibcode: 2013EJMin..25...78G. https://www.schweizerbart.de/papers/ejm/detail/25/79543/Ernstburkeite_MgCH3SO3212H2O_a_new_mineral_from_Antarctica.
- ↑ Ernstburkeite, MinDat.org, http://www.mindat.org/show.php?id=41897
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