Mesylate

Mesylate anion (structural formula)

Mesylate anion (ball-and-stick model)

In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (CH₃SO₃H). In salts, the mesylate is present as the CH₃SO−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 CH₃SO₂O−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 (CH₃SO₂) 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.^{[ citation needed ]}

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

1. International Nonproprietary Names Modified (PDF) (Report). World Health Organization. February 2006. INN Working Document 05.167/3. Retrieved 5 December 2008.
2. Smith, Michael B.; March, Jerry (2007). March's Advanced Organic Chemistry (6th ed.). John Wiley & Sons. p. 497. ISBN   978-0-471-72091-1.
3. 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).
4. Helferich, Burckhardt; Gnüchtel, Alfred (6 April 1938). "Ester der Methansulfonsäure in der Zuckergruppe" . Berichte der Deutschen Chemischen Gesellschaft (A and B Series) (in German). 71 (4): 712–718. doi:10.1002/cber.19380710403. ISSN   0365-9488.
5. Vaillancourt, Valerie; Cudahy, Michele M.; Kreilein, Matthew M.; Jacobs, Danielle L. (17 September 2007). "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.
6. Gupta D, Bhatia D, Dave V, Sutariya V, Varghese Gupta S (July 2018). "Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations". Molecules. 23 (7): 1719. doi: 10.3390/molecules23071719 . PMC   6100526 . PMID   30011904.
7. Elder DP, Delaney E, Teasdale A, Eyley S, Reif VD, Jacq K, Facchine KL, Oestrich RS, Sandra P, David F (July 2010). "The utility of sulfonate salts in drug development". J Pharm Sci. 99 (7): 2948–61. doi:10.1002/jps.22058. PMID   20112423.
8. 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. Bibcode:2013EJMin..25...78G. doi:10.1127/0935-1221/2013/0025-2257.
9. "Ernstburkeite". Mindat.org .