Hemithioacetal

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Hemithioacetal functional group

Hemithioacetal is an organic functional group with the general formula RCH(OR)SR.[1] They form in a spontaneous reaction between a thiol and an aldehyde. Since the formerly carbonyl carbon bears four different substituents, hemiacetals are chiral. Hemithioacetals are usually intermediates in the catalytic reactions and usually arise via acid or base catalysis. The hemithioacetal features vicinal hydroxyl and thioether functionalities. Although they are important intermediates, hemithioacetals are usually not isolated since they exist in equilibrium with the thiol and aldehyde:

RCHO + R’SH \overrightarrow{\leftarrow} RCH(OH)(SR’)

Isolable hemithioacetal[edit]

Hemithioacetals ordinarily readily dissociate into thiol and aldehyde. Some hemithioacetals have been isolated. The few isolable hemithioacetals are all cyclic, which disfavors dissociation. One example is 2-hydroxytetrahydrothiophene.[2] Another isolable hemithioacetal can be prepared by addition of thiol to methyl glyoxalate.[3] The stability of hemithioacetal is enhanced in the presence of acid.[4] Another class of isolable hemithioacetals are derived from carbonyl groups that form stable hydrates. For example, thiols react with hexafluoroacetone trihydrate to give hemithioacetals, which can be isolated.[5]

2-Hydroxytetrahydrothiophene is a rare example of a hemithioacetal that can be isolated.

Hemithioacetals in nature[edit]

Glyoxalase I, which is part of the glyoxalase system present in the cytosol, catalyzes the conversion of α-oxoaldehyde (RC(O)CHO) and the thiol glutathione (abbreviated GSH) to S-2-hydroxyacylglutathione derivatives [RCH(OH)CO-SG]. The catalytic mechanism involves an intermediate hemithioacetal adduct [RCOCH(OH)-SG]. The spontaneous reaction forms methylglyoxal-glutathione hemithioacetal and human glyoxalse I.[6]

A hemithioacetal is also invoked in the mechanism of prenylcysteine lyase. In catalytic mechanism, S-farnesylcysteine is oxidized by a flavin to a thiocarbenium ion. The thiocarbenium ion hydrolyzes to form the hemithioacetal:

[(RS)C(R’)(H)]+ + H2O → (RS)C(R’)(H)OH + H+

After formation, the hemithioacetal breaks into hydrogen peroxide, farnesal, and cysteine.[7]

References[edit]

  1. ^ Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, ISBN 0-471-72091-7 
  2. ^ Cox, J.M.; Owen, L.N., J. Chem. Soc. C, Cyclic hemithioacetals: Analogues of thiosugars with sulphur in the ring, 1967, 1130-1134. doi:10.1039/J39670001130
  3. ^ Milton, J; Brand, S; Jones, M.F; Rayner, C.M., Tetrahedron Letters, Enantioselective Enzymatic Synthesis of the Anti-Viral Agent Lamivudine, 1995, volume 36, 6961-6964, doi:10.1016/0040-4039(95)01380-Z
  4. ^ Barnett, R. E.; Jencks, W. P, J. Am. Chem. Soc, Diffusion-controlled and concerted catalysis in the decomposition of hemithioacetals, 1969, volume 91, 6758-6765. doi:10.1021/ja01052a038
  5. ^ Field, L.; Sweetman, B.J.; Bellas, M., Journal of Medicinal Chemistry, Biologically oriented organic sulfur chemistry. II. Formation of hemimercaptals or hemimercaptoles as a means of latentiating thiols, 1969, 12(4), 624-628. doi:10.1021/jm00304a014
  6. ^ Thornalley, P.J., Biochemical Society Transactions, Glyoxalase I - Structure, function and a critical role in the enzymatic defence against glycation, 2003, 31 (6), 1343-1348. ISSN: 03005127
  7. ^ Digits, J.A.; Pyun, H.-J.; Coates, R.M.; Casey, P.J. Journal of biological chemistry, Stereospecificity and kinetic mechanism of human prenylcysteine lyase, an unusual thioether oxidase, 2002, volume 277, 41086-41093. doi:10.1074/jbc.M208069200