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Retrosynthetic analysisFrom Wikipedia, the free encyclopedia

Retrosynthetic analysisis a technique for solving problems in the planning oforganic syntheses.This is

achieved by transforming a target molecule into simpler precursor structures without assumptions regardingstarting materials. Each precursor material is examined using the same method. This procedure is repeated

until simple or commercially available structures are reached.E.J. Coreyformalized this concept in his

book The Logic of Chemical Synthesis.[1][2][3]

The power of retrosynthetic analysis becomes evident in the design of a synthesis. The goal of retrosynthetic

analysis is structural simplification. Often, a synthesis will have more than one possible synthetic route.

Retrosynthesis is well suited for discovering different synthetic routes and comparing them in a logical and

straightfoward fashion.[4]

A database may be consulted at each stage of the analysis, to determine whether a

component already exists in the literature. In that case, no further exploration of that compound would be

required.

Contents

[hide]

1 Definitions

2 Example

3 Strategies

o 3.1 Functional group strategies

o 3.2 Stereochemical strategies

o 3.3 Structure-goal strategies

o 3.4 Transform-based strategies

o 3.5 Topological strategies

4 See also

5 References

6 External links

Definitions[edit]

Disconnection

A retrosynthetic step involving the breaking of a bond to form two (or more) synthons.

Retron

A minimal molecular substructure that enables certain transformations.

Retrosynthetic tree

http://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/Organic_synthesishttp://en.wikipedia.org/wiki/E.J._Coreyhttp://en.wikipedia.org/wiki/E.J._Coreyhttp://en.wikipedia.org/wiki/E.J._Coreyhttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-1http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-1http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-3http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-3http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-4http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-4http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-4http://en.wikipedia.org/wiki/Retrosynthetic_analysishttp://en.wikipedia.org/wiki/Retrosynthetic_analysishttp://en.wikipedia.org/wiki/Retrosynthetic_analysishttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Definitionshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Definitionshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Examplehttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Examplehttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Functional_group_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Functional_group_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Stereochemical_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Stereochemical_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Structure-goal_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Structure-goal_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Transform-based_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Transform-based_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Topological_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Topological_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#See_alsohttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#See_alsohttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Referenceshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Referenceshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#External_linkshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#External_linkshttp://en.wikipedia.org/w/index.php?title=Retrosynthetic_analysis&action=edit&section=1http://en.wikipedia.org/w/index.php?title=Retrosynthetic_analysis&action=edit&section=1http://en.wikipedia.org/w/index.php?title=Retrosynthetic_analysis&action=edit&section=1http://en.wikipedia.org/w/index.php?title=Retrosynthetic_analysis&action=edit&section=1http://en.wikipedia.org/wiki/Retrosynthetic_analysis#External_linkshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Referenceshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#See_alsohttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Topological_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Transform-based_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Structure-goal_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Stereochemical_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Functional_group_strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Strategieshttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Examplehttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#Definitionshttp://en.wikipedia.org/wiki/Retrosynthetic_analysishttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-4http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-3http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-1http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-1http://en.wikipedia.org/wiki/E.J._Coreyhttp://en.wikipedia.org/wiki/Organic_synthesis

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Adirected acyclic graphof several (or all) possible retrosyntheses of a single target.

Synthon

An idealized molecular fragment. A synthon and the corresponding commercially available synthetic

equivalentare shown below:

Target

The desired final compound.

Transform

The exact reverse of a synthetic reaction; the formation of starting materials from a single product.

example of retrosynthesis : paracetamol

Example[edit]

An example will allow the concept of retrosynthetic analysis to be easily understood.

In planning the synthesis ofphenylacetic acid,two synthons are identified. A

nucleophilic "-COOH" group, and an electrophilic "PhCH2+" group. Of course, both

synthons do not exist per se; synthetic equivalents corresponding to the synthons

are reacted to produce the desired product. In this case, thecyanide anionis the

synthetic equivalent for the-COOH synthon, whilebenzyl bromideis the synthetic

equivalent for the benzyl synthon.

The synthesis of phenylacetic acid determined by retrosynthetic analysis is thus:

PhCH2Br + NaCN PhCH2CN + NaBr

PhCH2CN + 2 H2O PhCH2COOH + NH3

http://en.wikipedia.org/wiki/Directed_acyclic_graphhttp://en.wikipedia.org/wiki/Directed_acyclic_graphhttp://en.wikipedia.org/wiki/Directed_acyclic_graphhttp://en.wikipedia.org/wiki/Synthonhttp://en.wikipedia.org/wiki/Synthonhttp://en.wikipedia.org/w/index.php?title=Retrosynthetic_analysis&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Retrosynthetic_analysis&action=edit&section=2http://en.wikipedia.org/w/index.php?title=Retrosynthetic_analysis&action=edit&section=2http://en.wikipedia.org/wiki/Phenylacetic_acidhttp://en.wikipedia.org/wiki/Phenylacetic_acidhttp://en.wikipedia.org/wiki/Phenylacetic_acidhttp://en.wikipedia.org/wiki/Cyanide_anionhttp://en.wikipedia.org/wiki/Cyanide_anionhttp://en.wikipedia.org/wiki/Cyanide_anionhttp://en.wikipedia.org/wiki/Benzyl_bromidehttp://en.wikipedia.org/wiki/Benzyl_bromidehttp://en.wikipedia.org/wiki/Benzyl_bromidehttp://en.wikipedia.org/wiki/File:Retrosynthetic_analysis_of_phenylacetic_acid.gifhttp://en.wikipedia.org/wiki/File:Synthon-example.gifhttp://en.wikipedia.org/wiki/File:Retrosynthetic_analysis_of_phenylacetic_acid.gifhttp://en.wikipedia.org/wiki/File:Synthon-example.gifhttp://en.wikipedia.org/wiki/Benzyl_bromidehttp://en.wikipedia.org/wiki/Cyanide_anionhttp://en.wikipedia.org/wiki/Phenylacetic_acidhttp://en.wikipedia.org/w/index.php?title=Retrosynthetic_analysis&action=edit&section=2http://en.wikipedia.org/wiki/Synthonhttp://en.wikipedia.org/wiki/Directed_acyclic_graph

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In fact, phenylacetic acid has been synthesized frombenzyl

cyanide,[5]

itself prepared by the analogous reaction ofbenzyl

chloridewithsodium cyanide.[6]

http://en.wikipedia.org/wiki/Benzyl_cyanidehttp://en.wikipedia.org/wiki/Benzyl_cyanidehttp://en.wikipedia.org/wiki/Benzyl_cyanidehttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-5http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-5http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-5http://en.wikipedia.org/wiki/Benzyl_chloridehttp://en.wikipedia.org/wiki/Benzyl_chloridehttp://en.wikipedia.org/wiki/Benzyl_chloridehttp://en.wikipedia.org/wiki/Benzyl_chloridehttp://en.wikipedia.org/wiki/Sodium_cyanidehttp://en.wikipedia.org/wiki/Sodium_cyanidehttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-6http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-6http://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-6http://en.wikipedia.org/wiki/File:Synthesis_of_phenylacetic_acid_english.svghttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-6http://en.wikipedia.org/wiki/Sodium_cyanidehttp://en.wikipedia.org/wiki/Benzyl_chloridehttp://en.wikipedia.org/wiki/Benzyl_chloridehttp://en.wikipedia.org/wiki/Retrosynthetic_analysis#cite_note-5http://en.wikipedia.org/wiki/Benzyl_cyanidehttp://en.wikipedia.org/wiki/Benzyl_cyanide