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[[Image:Hemithioacetal.png|150px|thumb|Hemithioacetal functional group]]

'''Hemithioacetal''' is an organic [[functional group]] with the general formula RCH(OR)SR.<ref name=March>{{March6th}}</ref> 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 (chemistry)|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 <math>\overrightarrow{\leftarrow}</math> RCH(OH)(SR’)

==Isolable hemithioacetal==
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-hydroxy[[tetrahydrothiophene]].<ref>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}}</ref> Another isolable hemithioacetal can be prepared by addition of thiol to methyl glyoxalate.<ref>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}}</ref> The stability of hemithioacetal is enhanced in the presence of acid.<ref>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}}</ref> 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.<ref>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}}</ref>
[[File:C4H7(OH)S.png|thumb|140px|left|2-Hydroxy[[tetrahydrothiophene]] is a rare example of a hemithioacetal that can be isolated.]]

==Hemithioacetals in nature==
[[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.<ref>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</ref>

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)]<sup>+</sup> + H2O → (RS)C(R’)(H)OH + H<sup>+</sup>
After formation, the hemithioacetal breaks into [[hydrogen peroxide]], farnesal, and [[cysteine]].<ref>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}}</ref>

==References==
{{Reflist}}

[[Category:Acetals]]
[[Category:Functional groups]]

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