thioestere

A thioester is a chemical functional group in which a carbonyl carbon is bonded to a sulfur atom from a thiol, described by the general structure R–CO–SR'. It is the sulfur analog of an ordinary ester, where the alkoxy group is replaced by a thioalkyl group. The carbonyl–sulfur linkage differs in resonance and sterics from the oxygen analog, often making thioesters more reactive toward nucleophilic attack and hydrolysis due to weaker resonance stabilization of the carbonyl by sulfur.

In biology, thioesters are central intermediates in acyl transfer reactions. The best-known example is acetyl-CoA and other acyl-CoA thioesters, which act as carriers of acyl groups in metabolism. They are formed by enzymes called acyl-CoA synthetases that activate carboxylic acids using ATP, yielding a high-energy thioester bond. Thioesters participate in fatty acid metabolism, the citric acid cycle, and various biosynthetic pathways, where the thioester linkage is often more reactive than an analogous oxygen ester, facilitating transfer of acyl groups to other nucleophiles such as CoA, amino groups, or enzyme active sites.

Laboratory synthesis of thioesters typically involves coupling carboxylic acids with thiols in the presence of coupling reagents (for example, DCC or EDC) or the reaction of acid chlorides with thiols. Alternative routes include formation from thioacids or transesterification-type processes. In addition to their role as reactive intermediates in organic synthesis, thioesters are used in peptide and protein chemistry, such as native chemical ligation, and as protecting or activating groups in selective acylation strategies.