Thioester
Encyclopedia
Thioesters are compounds with the functional group
C-S-CO-C. They are the product of esterification between a carboxylic acid
and a thiol
. Thioesters are widespread in biochemistry
, the best-known derivative being acetyl-CoA
.
A typical dehydration agent is DCC. Acid anhydrides and some lactone
s also react with thiols in the presence of base.
They also arise via carbonylation
of alkyne
s and alkene
s in the presence of thiols.
s:
The C-H groups adjacent to the carbonyl
in thioesters are mildly acidic and undergo aldol condensation
s. This kind of reaction occurs in the biosynthesis of fatty acids.
s and mevalonate, precursor to steroids. The biosynthesis of lignin
, which comprises a large fraction of biomass, proceeds via the thioester derivative of caffeic acid
. Examples include malonyl-CoA
, acetoacetyl-CoA
, propionyl-CoA
, cinnamoyl-CoA
. Acetogenesis
proceeds via the formation of acetyl-CoA. These thioesters arise analogously to those prepared synthetically, the difference being that the dehydration agent is ATP. In addition, thioesters play an important role in the tagging of proteins with ubiquitin, which tags the protein for degradation.
. Methyl thionobenzoate is C6H5C(S)OCH3. Such compounds are typically prepared by the reaction of the thioacyl chloride with an alcohol, but they can also be made by the reaction of Lawesson's reagent
with esters.
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
C-S-CO-C. They are the product of esterification between a carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
and a thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
. Thioesters are widespread in biochemistry
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
, the best-known derivative being acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
.
Synthesis
Thioesters have been prepared in many ways, but the main route involves condensation of thiols and carboxylic acids in the presence of dehydrating agents:- RSH + R'CO2H → RSC(O)R' + H2O
A typical dehydration agent is DCC. Acid anhydrides and some lactone
Lactone
In chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
s also react with thiols in the presence of base.
They also arise via carbonylation
Carbonylation
Carbonylation refers to reactions that introduce carbon monoxide into organic and inorganic substrates. Carbon monoxide is abundantly available and conveniently reactive, so it is widely used as a reactant in industrial chemistry.-Organic chemistry:...
of alkyne
Alkyne
Alkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature...
s and alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
s in the presence of thiols.
Reactions
The carbonyl center in thioesters is reactive toward nucleophiles, the reactivity being reminiscent of but milder than acid chlorides. Thus, thioesters and amines combine to give amideAmide
In chemistry, an amide is an organic compound that contains the functional group consisting of a carbonyl group linked to a nitrogen atom . The term refers both to a class of compounds and a functional group within those compounds. The term amide also refers to deprotonated form of ammonia or an...
s:
- R"NH2 + RSC(O)R' → R"2NC(O)R' + RSH
The C-H groups adjacent to the carbonyl
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
in thioesters are mildly acidic and undergo aldol condensation
Aldol condensation
An aldol condensation is an organic reaction in which an enol or an enolate ion reacts with a carbonyl compound to form a β-hydroxyaldehyde or β-hydroxyketone, followed by a dehydration to give a conjugated enone....
s. This kind of reaction occurs in the biosynthesis of fatty acids.
Biochemistry
Thioesters are common intermediates in many biosynthetic reactions, including the formation and degradation of fatty acidFatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s and mevalonate, precursor to steroids. The biosynthesis of lignin
Lignin
Lignin or lignen is a complex chemical compound most commonly derived from wood, and an integral part of the secondary cell walls of plants and some algae. The term was introduced in 1819 by de Candolle and is derived from the Latin word lignum, meaning wood...
, which comprises a large fraction of biomass, proceeds via the thioester derivative of caffeic acid
Caffeic acid
Caffeic acid is a hydroxycinnamic acid, a naturally occurring organic compound. This yellow solid consists of both phenolic and acrylic functional groups...
. Examples include malonyl-CoA
Malonyl-CoA
Malonyl-CoA is a coenzyme A derivative.-Functions:It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis....
, acetoacetyl-CoA
Acetoacetyl-CoA
Acetoacetyl CoA is the precursor of HMG-CoA in the Mevalonate pathway, which is essential for cholesterol synthesis. It also takes a similar role in the ketone bodies synthesis pathway of the liver...
, propionyl-CoA
Propionyl-CoA
Propionyl-CoA is a coenzyme A derivative of propionic acid.-Production:There are several different ways in which it is formed:* It is formed as a product of beta-oxidation of odd-chain fatty acids....
, cinnamoyl-CoA
Cinnamoyl-CoA:phenyllactate CoA-transferase
In enzymology, a cinnamoyl-CoA:phenyllactate CoA-transferase is an enzyme that catalyzes the chemical reaction-cinnamoyl-CoA + -phenyllactate \rightleftharpoons -cinnamate + -phenyllactyl-CoA...
. Acetogenesis
Acetogenesis
Acetogenesis is a process through which acetate is produced by anaerobic bacteria from a variety of energy and carbon sources. The different bacterial species that are capable of acetogenesis are collectively termed acetogens.-Biochemistry:The precursor to acetic acid is the thioester acetyl CoA...
proceeds via the formation of acetyl-CoA. These thioesters arise analogously to those prepared synthetically, the difference being that the dehydration agent is ATP. In addition, thioesters play an important role in the tagging of proteins with ubiquitin, which tags the protein for degradation.
Thioesters and the origin of life
As posited in a "Thioester World," thioesters are possible precursors to life. As de Duve explains:- It is revealing that thioesters are obligatory intermediates in several key processes in which ATP is either used or regenerated. Thioesters are involved in the synthesis of all esterEsterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s, including those found in complex lipidLipidLipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
s. They also participate in the synthesis of a number of other cellular components, including peptidePeptidePeptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s, fatty acidFatty acidIn chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
s, sterolSterolSterols, also known as steroid alcohols, are a subgroup of the steroids and an important class of organic molecules. They occur naturally in plants, animals, and fungi, with the most familiar type of animal sterol being cholesterol...
s, terpeneTerpeneTerpenes are a large and diverse class of organic compounds, produced by a variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium. They are often strong smelling and thus may have had a protective...
s, porphyrinPorphyrinPorphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
s, and others. In addition, thioesters are formed as key intermediates in several particularly ancient processes that result in the assembly of ATP. In both these instances, the thioester is closer than ATP to the process that uses or yields energy. In other words, thioesters could have actually played the role of ATP in a "thioester world" initially devoid of ATP. Eventually, [these] thioesters could have served to usher in ATP through its ability to support the formation of bonds between phosphate groups.
Isomeric compounds: thionoesters
Thionoesters are isomeric with thioesters. In a thionoester, sulfur replaces the carbonyl oxygen in an esterEster
Esters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
. Methyl thionobenzoate is C6H5C(S)OCH3. Such compounds are typically prepared by the reaction of the thioacyl chloride with an alcohol, but they can also be made by the reaction of Lawesson's reagent
Lawesson's reagent
Lawesson's reagent, or LR, is a chemical compound used in organic synthesis as a thiation agent. Lawesson's reagent was first made popular by Sven-Olov Lawesson, who did not, however, invent it. Lawesson's reagent was first made in 1956 during a systematic study of the reactions of arenes with...
with esters.