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Retrosyntheticanalysis
FromWikipedia,thefreeencyclopedia

Retrosyntheticanalysisisatechniqueforsolvingproblemsintheplanningoforganicsyntheses.Thisisachieved
bytransformingatargetmoleculeintosimplerprecursorstructureswithoutassumptionsregardingstarting
materials.Eachprecursormaterialisexaminedusingthesamemethod.Thisprocedureisrepeateduntilsimpleor
commerciallyavailablestructuresarereached.E.J.CoreyformalizedthisconceptinhisbookTheLogicof
ChemicalSynthesis.[1][2][3]

Thepowerofretrosyntheticanalysisbecomesevidentinthedesignofasynthesis.Thegoalofretrosynthetic
analysisisstructuralsimplification.Often,asynthesiswillhavemorethanonepossiblesyntheticroute.
Retrosynthesisiswellsuitedfordiscoveringdifferentsyntheticroutesandcomparingtheminalogicaland
straightfowardfashion.[4]Adatabasemaybeconsultedateachstageoftheanalysis,todeterminewhethera
componentalreadyexistsintheliterature.Inthatcase,nofurtherexplorationofthatcompoundwouldberequired.

Contents
1 Definitions
2 Example
3 Strategies
3.1 Functionalgroupstrategies
3.2 Stereochemicalstrategies
3.3 Structuregoalstrategies
3.4 Transformbasedstrategies
3.5 Topologicalstrategies
4 Seealso
5 References
6 Externallinks

Definitions
Disconnection
Aretrosyntheticstepinvolvingthebreakingofabondtoformtwo(ormore)synthons.
Retron
Aminimalmolecularsubstructurethatenablescertaintransformations.
Retrosynthetictree
Adirectedacyclicgraphofseveral(orall)possibleretrosynthesesofasingletarget.
Synthon
Anidealizedmolecularfragment.Asynthonandthecorrespondingcommerciallyavailablesynthetic
equivalentareshownbelow:

Target
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Thedesiredfinalcompound.
Transform
Thereverseofasyntheticreactiontheformationofstartingmaterialsfromasingleproduct.

Example
Anexamplewillallowtheconceptofretrosyntheticanalysistobeeasilyunderstood.

Inplanningthesynthesisofphenylaceticacid,twosynthonsareidentified.Anucleophilic"COOH"group,andan
electrophilic"PhCH2+"group.Ofcourse,bothsynthonsdonotexistpersesyntheticequivalentscorrespondingto
thesynthonsarereactedtoproducethedesiredproduct.Inthiscase,thecyanideanionisthesyntheticequivalent
fortheCOOHsynthon,whilebenzylbromideisthesyntheticequivalentforthebenzylsynthon.

Thesynthesisofphenylaceticaciddeterminedbyretrosyntheticanalysisisthus:

PhCH2Br+NaCNPhCH2CN+NaBr
PhCH2CN+2H2OPhCH2COOH+NH3

Infact,phenylaceticacidhasbeensynthesizedfrombenzylcyanide,[5]itselfpreparedbytheanalogousreactionof
benzylchloridewithsodiumcyanide.[6]

Strategies
Functionalgroupstrategies

Manipulationoffunctionalgroupscanleadtosignificantreductionsinmolecularcomplexity.

Stereochemicalstrategies

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Numerouschemicaltargetshavedistinctstereochemicaldemands.Stereochemicaltransformations(suchasthe
ClaisenrearrangementandMitsunobureaction)canremoveortransferthedesiredchiralitythussimplifyingthe
target.

Structuregoalstrategies

Directingasynthesistowardadesirableintermediatecangreatlynarrowthefocusofananalysis.Thisallows
bidirectionalsearchtechniques.

Transformbasedstrategies

Theapplicationoftransformationstoretrosyntheticanalysiscanleadtopowerfulreductionsinmolecular
complexity.Unfortunately,powerfultransformbasedretronsarerarelypresentincomplexmolecules,and
additionalsyntheticstepsareoftenneededtoestablishtheirpresence.

Topologicalstrategies

Theidentificationoneormorekeybonddisconnectionsmayleadtotheidentificationofkeysubstructuresor
difficulttoidentifyrearrangementtransformations.

Disconnectionsthatpreserveringstructuresareencouraged.
Disconnectionsthatcreateringslargerthan7membersarediscouraged.

Seealso
Organicsynthesis
Totalsynthesis

References
1.E.J.Corey,XM.Cheng(1995).TheLogicofChemicalSynthesis.NewYork:Wiley.ISBN0471115940.
2.E.J.Corey(1988)."RetrosyntheticThinkingEssentialsandExamples".Chem.Soc.Rev.17:111133.
doi:10.1039/CS9881700111.
3.E.J.Corey(1991)."TheLogicofChemicalSynthesis:MultistepSynthesisofComplexCarbogenicMolecules(Nobel
Lecture)"(Reprint).AngewandteChemieInternationalEditioninEnglish.30(5):455465.doi:10.1002/anie.199104553.
4.JamesLawet.al:"RouteDesigner:ARetrosyntheticAnalysisToolUtilizingAutomatedRetrosyntheticRuleGeneration",
JournalofChemicalInformationandModelling(ACSJCIM)PublicationDate(Web):February6,2009
doi:10.1021/ci800228y(https://dx.doi.org/10.1021%2Fci800228y),http://pubs.acs.org/doi/abs/10.1021/ci800228y
5.WilhelmWenner(1963)."Phenylacetamide".Org.Synth.Coll.Vol.,4,p.760
6.RogerAdamsA.F.Thal(1941)."BenzylCyanide".Org.Synth.Coll.Vol.,1,p.107

Externallinks
CentreforMolecularandBiomolecularInformatics(http://cheminf.c
Wikiquotehasquotations
mbi.ru.nl/cheminf/ira/) relatedto:Retrosynthetic
PresentationonARChemRouteDesigner,ACS,Philadelphia, analysis
September2008(http://www.slideshare.net/AntonyWilliams/anewa
utomatedretrosyntheticsearchenginearchempresentation)formoreinfoonARChemseetheSimBioSys
pages.
Retrosynthesisplanningtool:ICSynthbyInfoChem(http://infochem.de/products/software/icsynth.shtml)

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Categories: Chemicalsynthesis Organicchemistry Chemicalreactionengineering

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