# Active ester

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In [organic chemistry](/source/organic_chemistry), an '''active ester''' is an [ester](/source/ester) [functional group](/source/functional_group) that is highly susceptible toward nucleophilic attack. Activation can be imparted by modifications of the acyl or the alkoxy components of a normal ester, say [ethyl acetate](/source/ethyl_acetate). Typical modifications call for electronegative substituents. Active esters are employed in both synthetic and biological chemistry.  
[[File:Acetyl-CoA-2D_colored.svg|thumb|right|[Acetyl CoA](/source/Acetyl_CoA) is the prototypical active ester in [biosynthesis](/source/biosynthesis).]]

==Reactivity==
Active esters are mainly used as [acylating agents](/source/acylation). They undergo the same reactions as their unactivated analogues but do so more rapidly. They are prone to [hydrolysis](/source/hydrolysis), for example.  Of great interest is the enhanced reactivity of active esters toward [amine](/source/amine)s to give [amide](/source/amide)s.<ref name=Joullié>{{cite journal|journal=Arkivoc|year=2010|volume=viii|pages=189–250|title=Evolution of Amide Bond Formation|author1=Madeleine M. Joullié |author2=Kenneth M. Lassen|url=http://www.arkat-usa.org/get-file/34631/}}</ref><ref>{{cite journal |doi=10.1021/cr100048w |title=Peptide Coupling Reagents, More than a Letter Soup |date=2011 |last1=El-Faham |first1=Ayman |last2=Albericio |first2=Fernando |journal=Chemical Reviews |volume=111 |issue=11 |pages=6557–6602 |pmid=21866984 }}</ref>

==Examples==
===Biochemistry===
[[image:3'-Phosphoadenosine-5'-phosphosulfate.svg|thumb|right|120px|[3'-Phosphoadenosine-5'-phosphosulfate](/source/3'-Phosphoadenosine-5'-phosphosulfate) is an active ester of sulfate.<ref>{{cite journal |author =Günal S |author2 =Hardman R |author3 =Kopriva S |author4 =Mueller JW |title=Sulfation pathways from red to green |journal=J. Biol. Chem. |volume=294 |issue=33 |pages=12293–12312 |year=2019 |pmid=31270211 |doi=10.1074/jbc.REV119.007422|doi-access=free |pmc=6699852 }}</ref>]]
Active esters are prominent in biochemistry.  [Glutamine synthetase](/source/Glutamine_synthetase) is an enzyme that forms an active ester from the terminal carboxylate of glutamic acid.  This activation, imparted by phosphorylation, facilitates the conversion of the carboxylate to an amide called [glutamine](/source/glutamine).<ref name=BigRev>{{cite journal |doi=10.1016/s0167-4838(99)00270-8 |title=Structure–function relationships of glutamine synthetases |date=2000 |last1=Eisenberg |first1=David |last2=Gill |first2=Harindarpal S. |last3=Pfluegl |first3=Gaston M.U. |last4=Rotstein |first4=Sergio H. |journal=Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology |volume=1477 |issue=1–2 |pages=122–145 |pmid=10708854 }}</ref>
center|alt=Glutamine synthetase reaction. |Glutamine synthetase catalyzed reaction

[Thioester](/source/Thioester)s are prominent active esters, as illustrated by the esters of [coenzyme A](/source/coenzyme_A).<ref>{{cite journal|title=Polypeptide synthesis by the thioester method|author=Aimoto, Saburo
|journal=Biopolymers|year=1999|volume=51|issue=4
|pages=247–265|doi=10.1002/(SICI)1097-0282(1999)51:4<247::AID-BIP2>3.0.CO;2-W|pmid=10618594
}}</ref>

[Terpene](/source/Terpene)s and terpenoids are generated from active esters.  Some biosynthetically significant active esters include [isopentenyl pyrophosphate](/source/isopentenyl_pyrophosphate), [dimethylallyl pyrophosphate](/source/dimethylallyl_pyrophosphate), and [geranyl pyrophosphate](/source/geranyl_pyrophosphate).
[[File:Sterol synthesis.svg|thumb|right|350px|Simplified version of the steroid synthesis pathway with the active ester intermediates isopentenyl pyrophosphate (IPP), dimethylallyl pyrophosphate (DMAPP), [geranyl pyrophosphate](/source/geranyl_pyrophosphate) (GPP) and squalene shown. Some intermediates are omitted.]]

===Synthetic chemistry===
350px|thumb|right|Use of hydroxybenzotriazole to form an active ester.
[Hydroxybenzotriazole](/source/Hydroxybenzotriazole) is used in [peptide synthesis](/source/peptide_synthesis) by forming an active ester from acyl isoureas.<ref>{{cite journal |doi=10.1021/cr100048w |title=Peptide Coupling Reagents, More than a Letter Soup |date=2011 |last1=El-Faham |first1=Ayman |last2=Albericio |first2=Fernando |journal=Chemical Reviews |volume=111 |issue=11 |pages=6557–6602 |pmid=21866984 }}</ref>

Classically, activated esters are derivatives of [nitrophenol](/source/nitrophenol)s and [pentafluorophenol](/source/pentafluorophenol).  These esters react with nucleophiles much more rapidly than the related aryl and especially alkyl esters.

Active esters of [acrylic acid](/source/acrylic_acid) are precursors to polymers with reactive side chains.<ref>{{cite journal|title=Activated Ester Containing Polymers: Opportunities and Challenges for the Design of Functional Macromolecules|author1=Anindita Das |author2=Patrick Theato|journal=Chem. Rev.|year=2016|volume=116|issue=3 |pages=1434–1495|doi=10.1021/acs.chemrev.5b00291|pmid=26305991 }}</ref>

The concept of active esters extends to esters of phosphoric and [sulfuric acid](/source/sulfuric_acid)s. One such case is [dimethylsulfate](/source/dimethylsulfate), a strong [methylating agent](/source/methylating_agent).

==References==
<references />

Category:Functional groups
Category:Esters

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Adapted from the Wikipedia article [Active ester](https://en.wikipedia.org/wiki/Active_ester) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Active_ester?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.