thiolactone
Thiolactones are a class of heterocyclic compounds in organic chemistry. They are analogs of the more common lactones in which an oxygen atom is replaced with a sulfur atom. The sulfur atom is within the ring system and adjacent to a carbonyl group.
Chemistry
Thiolactones can be prepared by dehydration of thiol-containing carboxylic acids. Thiolactones can be hydrolyzed back to the thiol acids under basic conditions.{{cite journal|last1=Stevens|first1=Charles|last2=Tarbell|first2=D. Stanley|title=The Kinetics of Basic Hydrolysis Of Some γ-Lactones and γ-Thiolactones In Aqueous Acetone|journal=The Journal of Organic Chemistry|date=December 1954|volume=19|issue=12|pages=1996–2003|doi=10.1021/jo01377a017}} β-Thiolactones can be opened by reaction at the 4-position via SN2 nucleophilic reactions.{{cite journal | doi = 10.1021/jo9001728 | title = SN2-Type Nucleophilic Opening of β-Thiolactones (Thietan-2-ones) as a Source of Thioacids for Coupling Reactions | year = 2009 | last1 = Crich | first1 = David | last2 = Sana | first2 = Kasinath | journal = The Journal of Organic Chemistry | volume = 74 | issue = 9 | pages = 3389–3393 | pmid = 19388715}}
Occurrence
File:Clopidogrel activation.svg (top left) gives a thiolactone, which ring-opens.
{{cite journal| vauthors = Pereillo JM, Maftouh M, Andrieu A, Uzabiaga MF, Fedeli O, Savi P, Pascal M, Herbert JM, Maffrand JP, Picard C| year = 2002| title = Structure and stereochemistry of the active metabolite of clopidogrel| journal = Drug Metab. Dispos.| volume = 30| issue = 11| pages = 1288–95| pmid = 12386137| doi = 10.1124/dmd.30.11.1288| s2cid = 2493588 }}]]
Thiolactones are intermediates in the activation of some drugs.{{cite journal |doi=10.1177/0091270009343005 |title=Metabolism and Disposition of the Thienopyridine Antiplatelet Drugs Ticlopidine, Clopidogrel, and Prasugrel in Humans |date=2010 |last1=Farid |first1=Nagy A. |last2=Kurihara |first2=Atsushi |last3=Wrighton |first3=Steven A. |journal=The Journal of Clinical Pharmacology |volume=50 |issue=2 |pages=126–142 |pmid=19948947 }}
In nature, the most common thiolactone is homocysteine thiolactone. It is produced from homocysteine. It may play a role in protein damage.{{cite journal | pmid = 10721911 | year = 2000 | last1 = Jakubowski | first1 = H | title = Homocysteine thiolactone: Metabolic origin and protein homocysteinylation in humans | volume = 130 | issue = 2S Suppl | pages = 377S–381S | journal = The Journal of Nutrition| doi = 10.1093/jn/130.2.377S | doi-access = free }} The drugs citiolone and erdosteine are modified versions of homocysteine thiolactone.
Thiolactones have been found in peptides synthesized by bacteria such as Staphylococcus aureus in order to regulate their quorum-sensing system.{{cite journal | year = 2007 | last1 = Malone | first1 = C.L | title = Biosynthesis of Staphylococcus aureus Autoinducing Peptides by using the Synechocystis DnaB Mini-Intein | volume = 73 | issue = 19 | pages= 6036–6044 | journal = Applied and Environmental Microbiology | doi=10.1128/aem.00912-07 | pmid=17693565 | pmc=2074992| bibcode = 2007ApEnM..73.6036M }}