Active ester
In organic chemistry, an active ester is an ester 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. Typical modifications call for electronegative substituents. Active esters are employed in both synthetic and biological chemistry.
File:Acetyl-CoA-2D_colored.svg is the prototypical active ester in biosynthesis.]]
Reactivity
Active esters are mainly used as acylating agents. They undergo the same reactions as their unactivated analogues but do so more rapidly. They are prone to hydrolysis, for example. Of great interest is the enhanced reactivity of active esters toward amines to give amides.{{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/}}{{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 }}
Examples
=Biochemistry=
image:3'-Phosphoadenosine-5'-phosphosulfate.svg is an active ester of sulfate.{{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 }}]]
Active esters are prominent in biochemistry. 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.{{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 }}
File:Glutamine_synthetase_reaction.svg
Thioesters are prominent active esters, as illustrated by the esters of coenzyme A.{{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
}}
Terpenes and terpenoids are generated from active esters. Some biosynthetically significant active esters include isopentenyl pyrophosphate, dimethylallyl pyrophosphate, and geranyl pyrophosphate.
File:Sterol synthesis.svg (GPP) and squalene shown. Some intermediates are omitted.]]
=Synthetic chemistry=
Hydroxybenzotriazole is used in peptide synthesis by forming an active ester from acyl isoureas.{{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 }}
Classically, activated esters are derivatives of nitrophenols and pentafluorophenol. These esters react with nucleophiles much more rapdily than the related aryl and especially alkyl esters.
Active esters of acrylic acid are precursors to polymers with reactive side chains.{{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 }}
The concept of active esters extends to esters of phosphoric and sulfuric acids. One such case is dimethylsulfate, a strong methylating agent.