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Thioester

Thioester is a mathematics topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Thioester rather than just read about it. In short: In organic chemistry, thioesters are organosulfur compounds with the molecular structure R−C(=O)−S−R'. They are analogous to carboxylate esters (R−C(=O)−O−R') with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix.

Thioester — main illustration
Thioester — illustration

Key takeaways

  • Thioester belongs to mathematics; place it in that map before memorising details.
  • Learn the definition first, then one example that makes the definition concrete.
  • Connect Thioester to a quantity you can measure, compute or draw — that is where exam questions come from.
  • Reproduce the core statement of Thioester from memory before moving on to harder problems.

Reference excerpt

In organic chemistry, thioesters are organosulfur compounds with the molecular structure R−C(=O)−S−R'. They are analogous to carboxylate esters (R−C(=O)−O−R') with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix. They are the product of esterification of a carboxylic acid (R−C(=O)−O−H) with a thiol (R'−S−H). In biochemistry, the best-known thioesters are derivatives of coenzyme A, e.g., acetyl-CoA. The R and R' represent organyl groups, or H in the case of R.

Synthesis One route to thioesters involves the reaction of an acid chloride with an alkali metal salt of a thiol:

RSNa + R'COCl → R'COSR + NaCl Another common route entails the displacement of halides by the alkali metal salt of a thiocarboxylic acid. (The analogous alkylation of a carboxylate salt is rarely practiced.) For example, thioacetate esters are commonly prepared by alkylation of potassium thioacetate:

CH3COSK + RX → CH3COSR + KX The alkylation can be conducted using Mannich bases and the thiocarboxylic acid:

CH3COSH + R'2NCH2OH → CH3COSCH2NR'2 + H2O Thioesters can be prepared by 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. Efforts to improve the sustainability of thioester synthesis have also been reported utilising safer coupling reagent T3P and greener solvent cyclopentanone. Acid anhydrides and some lactones also give thioesters upon treatment with thiols in the presence of a base. Thioesters can be conveniently prepared from alcohols by the Mitsunobu reaction, using thioacetic acid. They also arise via carbonylation of alkynes and alkenes in the presence of thiols.

Reactions Thioesters hydrolyze to thiols and the carboxylic acid:

RC(O)SR' + H2O → RCO2H + RSH The carbonyl center in thioesters is more reactive toward amine than oxygen nucleophiles, giving amides:

This reaction is exploited in native chemical ligation, a protocol for peptide synthesis. In a related reaction, thioesters can be converted into esters. Thioacetate esters can also be cleaved with methanethiol in the presence of stoichiometric base, as illustrated in the preparation of pent-4-yne-1-thiol:

H3C(CH2)3OMs + KSAc → H3C(CH2)3SAc + KOMs H3C(CH2)3SAc + HSMe → H3C(CH2)3SH + MeSAc Thioesters enolize easily as the sulfur atom stabilizes the enol. But the enols are less nucleophilic than ketene acetals, and carbonyl α-substitution reactions occur more slowly. A reaction unique to thioesters is the Fukuyama coupling, in which the thioester is coupled with an organozinc halide by a palladium catalyst to give a ketone.

Biochemistry

Thioesters are common intermediates in many biosynthetic reactions, including the formation and degradation of fatty acids and mevalonate, precursor to steroids. Examples include malonyl-CoA, acetoacetyl-CoA, propionyl-CoA, cinnamoyl-CoA, and acyl carrier protein (ACP) thioesters. Acetogenesis proceeds via the formation of acetyl-CoA. The biosynthesis of lignin, which comprises a large fraction of the Earth's land biomass, proceeds via a thioester derivative of caffeic acid. 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. Oxidation of the sulfur atom in thioesters (thiolactones) is postulated in the bioactivation of the antithrombotic prodrugs ticlopidine, clopidogrel, and prasugrel.

Thioesters and the origin of life As posited in a "Thioester World", thioesters are possible precursors to life. As Christian 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 esters, including those found in complex lipids. They also participate in the synthesis of a number of other cellular components, including peptides, fatty acids, sterols, terpenes, porphyrins, 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. However, due to the high free energy change of thioester's hydrolysis and correspondingly their low equilibrium constants, it is unlikely that these compounds could have accumulated abiotically to any significant extent especially in hydrothermal vent conditions.

Thionoesters

Thionoesters are isomeric with thioesters. In a thionoester, sulfur replaces the carbonyl oxygen in an ester. Methyl thionobenzoate is C6H5C(S)OCH3. Such compounds are typically prepared by the reaction of the thioacyl chloride with an alcohol.

They can also be made by the reaction of Lawesson's reagent with esters or by treating pinner salts with hydrogen sulfide. Various thionoesters may be prepared through the transesterification of an existing methyl thionoester with an alcohol under base-catalyzed conditions.

Xanthates and thioamides can be transformed to thionoesters under metal-catalyzed cross-coupling conditions.

See also Thiocarboxylic acid Thiocarbonate Liebeskind–Srogl coupling Aldrithiol-2

References

Illustrations

Thioester: General structure of a thioester, where R and R' are organyl groups, or H in the case of R.
General structure of a thioester, where R and R' are organyl groups, or H in the case of R.
Thioester illustration
Thioester: Thioesters are components of the native chemical ligation method for peptide synthesis.
Thioesters are components of the native chemical ligation method for peptide synthesis.
Thioester illustration
Thioester: Structure of acetyl coenzyme A, a thioester that is a key intermediate in the biosynthesis of many biomolecules.
Structure of acetyl coenzyme A, a thioester that is a key intermediate in the biosynthesis of many biomolecules.

Worked examples

Example 1 — a first encounter with Thioester

Start with the simplest possible case. Write down what Thioester claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In mathematics, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Thioester before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Thioester ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Thioester

In research
Thioester appears in mathematics research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry
Engineering practice reuses Thioester in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom
Thioester is common in secondary-school and first-year university syllabi. It links to neighbouring topics Functional groups, Origin of life, Thioesters, so understanding it makes those chapters shorter.
In everyday life
Look for Thioester outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Thioester in 20 minutes

  1. Read the reference excerpt below once, without taking notes.
  2. Close the page and write down what Thioester means in your own words.
  3. Compare your version with the excerpt and mark what you missed.
  4. Work through the three examples above with pen and paper.
  5. Explain Thioester out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Thioester in simple terms?

In organic chemistry, thioesters are organosulfur compounds with the molecular structure R−C(=O)−S−R'. They are analogous to carboxylate esters (R−C(=O)−O−R') with the sulfur in the thioester replacing oxygen in the carboxylate ester, as implied by the thio- prefix.

Why does Thioester matter?

Because it connects several mathematics ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Thioester?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Thioester.

Tags

  • Functional groups
  • Origin of life
  • Thioesters

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