Difference between revisions of "Organic synthesis"
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| − | '' | + | '''Organic synthesis''' is a special branch of [[chemical synthesis]] and is concerned with the construction of [[organic compound]]s via [[organic reaction]]s. [[Organic chemistry|Organic]] molecules can often contain a higher level of complexity compared to purely [[Inorganic chemistry|inorganic]] compounds, so the synthesis of [[organic compound]]s has developed into one of the most important branches of [[organic chemistry]]. There are two main areas of research fields within the general area of organic synthesis: ''[[total synthesis]]'' and ''[[methodology]]''. |
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== Total synthesis == | == Total synthesis == | ||
{{main|Total synthesis}} | {{main|Total synthesis}} | ||
| − | A total synthesis<ref>{{cite book | last = Nicolaou | first = K. C. | authorlink = K. C. Nicolaou | coauthors = Sorensen, E. J. | title = Classics in Total Synthesis | publisher = [[VCH]] | date = 1996 | location = New York }}</ref> is the complete [[chemical synthesis]] of complex [[ | + | A total synthesis<ref>{{cite book | last = Nicolaou | first = K. C. | authorlink = K. C. Nicolaou | coauthors = Sorensen, E. J. | title = Classics in Total Synthesis | publisher = [[VCH]] | date = 1996 | location = New York }}</ref> is the complete [[chemical synthesis]] of complex [[Organic compound|organic]] [[molecule]]s from simple, commercially available ([[petrochemical]]) or [[nature|natural]] precursors. In a ''linear'' synthesis there is a series of steps which are performed one after another until the molecule is made- this is often adequate for a simple structure. The chemical compounds made in each step are usually referred to as ''synthetic intermediates''. For more complex molecules, a [[convergent synthesis]] is often preferred. This is where several "pieces" (key intermediates) of the final product are synthesized separately, then coupled together, often near the end of the synthesis. |
| − | The "father" of modern organic synthesis is regarded as [[Robert Burns Woodward]], who received the 1965 [[Nobel Prize for Chemistry]] for several brilliant examples of total synthesis such as his 1954 synthesis of [[strychnine]]<ref>{{cite journal | last = Woodward | first = R. B. | authorlink = Robert Burns Woodward | coauthors = Cava, M. P.; Ollis, W. D.; Hunger, A.; Daeniker, H. U.; Schenker, K. | title = The Total Synthesis of Strychnine | journal = [[Journal of the American Chemical Society]] | volume = 76 | issue = 18 | pages = 4749–4751 | date = 1954 | url = http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1954/76/i18/pdf/ja01647a088.pdf | format = [[PDF]] subscription required }} | + | The "father" of modern organic synthesis is regarded as [[Robert Burns Woodward]], who received the 1965 [[Nobel Prize for Chemistry]] for several brilliant examples of total synthesis such as his 1954 synthesis of [[strychnine]]<ref>{{cite journal | last = Woodward | first = R. B. | authorlink = Robert Burns Woodward | coauthors = Cava, M. P.; Ollis, W. D.; Hunger, A.; Daeniker, H. U.; Schenker, K. | title = The Total Synthesis of Strychnine | journal = [[Journal of the American Chemical Society]] | volume = 76 | issue = 18 | pages = 4749–4751 | date = 1954 | url = http://pubs.acs.org/cgi-bin/searchRedirect.cgi/jacsat/1954/76/i18/pdf/ja01647a088.pdf | format = [[PDF]] subscription required | doi = 10.1021/ja01647a088 }} |
</ref>. Some modern examples include Wender's, [[Holton Taxol total synthesis|Holton's]], [[Nicolaou Taxol total synthesis|Nicolaou's]] and [[Danishefsky Taxol total synthesis|Danishefsky's synthesis of Taxol]]. | </ref>. Some modern examples include Wender's, [[Holton Taxol total synthesis|Holton's]], [[Nicolaou Taxol total synthesis|Nicolaou's]] and [[Danishefsky Taxol total synthesis|Danishefsky's synthesis of Taxol]]. | ||
== Methodology == | == Methodology == | ||
| − | + | Each step of a synthesis involves a [[chemical reaction]], and [[reagent]]s and conditions for each of these reactions need to be designed to give a good yield and a pure product, with as little work as possible<ref>{{cite book | last = March | first = J. | coauthors = Smith, D. | title = Advanced Organic Chemistry, 5<sup>th</sup> ed | publisher = [[John Wiley & Sons|Wiley]] | date = 2001 | location = New York }}</ref>. A method may already exist in the literature for making one of the early synthetic intermediates, and this method will usually be used rather than "trying to reinvent the wheel". However most intermediates are compounds that have never been made before, and these will normally be made using general methods developed by methodology researchers. To be useful, these methods need to give high [[yield]]s and to be reliable for a broad range of [[Substrate (chemistry)|substrate]]s. Methodology research usually involves three main stages- ''[[Discovery (observation)|discovery]]'', ''[[optimisation]]'', and studies of ''scope and limitations''. The ''discovery'' requires extensive knowledge of and experience with chemical reactivities of appropriate reagents. ''Optimisation'' is where one or two starting compounds are tested in the reaction under a wide variety of conditions of temperature, solvent, reaction time, etc., until the optimum conditions for product yield and purity are found. Then the researcher tries to extend the method to a broad range of different starting materials, to find the scope and limitations. Some larger research groups may then perform a total synthesis (see above) to showcase the new methodology and demonstrate its value in a real application. | |
| − | Each step of a synthesis involves a [[chemical reaction]], and | ||
== Asymmetric synthesis == | == Asymmetric synthesis == | ||
{{main|Chiral synthesis}} | {{main|Chiral synthesis}} | ||
| − | Many complex natural products occur as one pure [[enantiomer]]. Traditionally, however, a total synthesis could | + | Many complex natural products occur as one pure [[enantiomer]]. Traditionally, however, a total synthesis could only make a complex molecule as a [[Racemate|racemic]] mixture, i.e., as an equal mixture of both possible [[enantiomer]] forms. The racemic mixture might then be separated via [[chiral resolution]]. |
In the latter half of the twentieth century, chemists began to develop methods of asymmetric [[catalysis]] and [[kinetic resolution]] whereby reactions could be directed to produce only one enantiomer rather than a racemic mixture. Early examples include [[Sharpless epoxidation]] ([[K. Barry Sharpless]]) and asymmetric [[hydrogenation]] ([[William S. Knowles]] and [[Ryoji Noyori]]), and these workers went on to share the [[Nobel Prize in Chemistry]] in 2001 for their discoveries. Such reactions gave chemists a much wider choice of enantiomerically pure molecules to start from, where previously only natural starting materials could be used. Using techniques pioneered by [[Robert B. Woodward]] and new developments in synthetic methodology, chemists became more able to take simple molecules through to more complex molecules without unwanted racemisation, by understanding [[stereocontrol]]. This allowed the final target molecule to be synthesised as one pure enantiomer without any resolution being necessary. Such techniques are referred to as '''asymmetric synthesis'''. | In the latter half of the twentieth century, chemists began to develop methods of asymmetric [[catalysis]] and [[kinetic resolution]] whereby reactions could be directed to produce only one enantiomer rather than a racemic mixture. Early examples include [[Sharpless epoxidation]] ([[K. Barry Sharpless]]) and asymmetric [[hydrogenation]] ([[William S. Knowles]] and [[Ryoji Noyori]]), and these workers went on to share the [[Nobel Prize in Chemistry]] in 2001 for their discoveries. Such reactions gave chemists a much wider choice of enantiomerically pure molecules to start from, where previously only natural starting materials could be used. Using techniques pioneered by [[Robert B. Woodward]] and new developments in synthetic methodology, chemists became more able to take simple molecules through to more complex molecules without unwanted racemisation, by understanding [[stereocontrol]]. This allowed the final target molecule to be synthesised as one pure enantiomer without any resolution being necessary. Such techniques are referred to as '''asymmetric synthesis'''. | ||
== Synthesis design == | == Synthesis design == | ||
| − | + | [[Elias James Corey]] brought a more formal approach to synthesis design, based on [[retrosynthetic analysis]], for which he won the [[Nobel Prize for Chemistry]] in 1990. In this approach, the research is planned backwards from the product, using standard rules<ref>{{cite book | last = Corey | first = E. J. | authorlink = Elias James Corey | coauthors = Cheng, X-M. | title = The Logic of Chemical Synthesis | publisher = [[John Wiley & Sons|Wiley]] | date = 1995 | location = New York }}</ref>. The steps are shown using retrosynthetic arrows (drawn as =>), which in effect means "is made from". Other workers in this area include one of the pioneers of [[computational chemistry]], [[James B. Hendrickson]], who developed a computer program for designing a synthesis based on sequences of generic "half-reactions". Computer-aided methods have recently been reviewed.<ref>{{cite journal | last = Todd | first = Matthew H. | title = Computer-aided Organic Synthesis | journal = [[Chemical Society Reviews]] | volume = 34 | pages = 247–266 | year = 2005 | doi = 10.1039/b104620a }}</ref> | |
| − | [[Elias James Corey]] brought a more formal approach to synthesis design, based on [[retrosynthetic analysis]], for which he won the [[Nobel Prize for Chemistry]] in 1990. In this approach, the research is planned backwards from the product, using standard rules<ref>{{cite book | last = Corey | first = E. J. | authorlink = Elias James Corey | coauthors = Cheng, X-M. | title = The Logic of Chemical Synthesis | publisher = [[John Wiley & Sons|Wiley]] | date = 1995 | location = New York }}</ref>. The steps are shown using retrosynthetic arrows (drawn as =>), which in effect means "is made from". Other workers in this area include one of the pioneers of [[computational chemistry]], [[James B. Hendrickson]], who developed a computer program for designing a synthesis based on sequences of generic "half-reactions" | ||
== See also == | == See also == | ||
| − | [[Organic Syntheses]], a publication which gives detailed peer-tested laboratory procedures. | + | *[[Organic Syntheses]], a publication which gives detailed peer-tested laboratory procedures. |
| + | *[[Methods in Organic Synthesis]], a journal | ||
== References == | == References == | ||
| − | + | {{Reflist}} | |
==External links== | ==External links== | ||
| − | + | {{Commons cat|Organic syntheses}} | |
| + | * [http://www.chemsynthesis.com Chemical synthesis database] | ||
* http://www.webreactions.net/search.html | * http://www.webreactions.net/search.html | ||
* http://www.organic-chemistry.org/synthesis/ | * http://www.organic-chemistry.org/synthesis/ | ||
| + | * [http://www.chem.wisc.edu/areas/reich/syntheses/syntheses.htm Natural product syntheses] | ||
| + | <!--* [http://wikisynth.net Chemical synthesis semantic wiki]--> | ||
| + | * [http://www.orgachemistryhelp.com/articles/organic-chemistry-synthesis.html Organic Chemistry Synthesis Approach and Modern Development] | ||
| + | |||
| + | {{Organic chemistry}} | ||
[[Category:Organic chemistry]] | [[Category:Organic chemistry]] | ||
| + | [[Category:Synthetic organic chemistry|*]] | ||
| + | |||
| + | {{Imported from Wikipedia|name=Organic synthesis|id=303057751}} | ||
Latest revision as of 15:00, 9 August 2009
Organic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has developed into one of the most important branches of organic chemistry. There are two main areas of research fields within the general area of organic synthesis: total synthesis and methodology.
Contents
Total synthesis
A total synthesis[1] is the complete chemical synthesis of complex organic molecules from simple, commercially available (petrochemical) or natural precursors. In a linear synthesis there is a series of steps which are performed one after another until the molecule is made- this is often adequate for a simple structure. The chemical compounds made in each step are usually referred to as synthetic intermediates. For more complex molecules, a convergent synthesis is often preferred. This is where several "pieces" (key intermediates) of the final product are synthesized separately, then coupled together, often near the end of the synthesis.
The "father" of modern organic synthesis is regarded as Robert Burns Woodward, who received the 1965 Nobel Prize for Chemistry for several brilliant examples of total synthesis such as his 1954 synthesis of strychnine[2]. Some modern examples include Wender's, Holton's, Nicolaou's and Danishefsky's synthesis of Taxol.
Methodology
Each step of a synthesis involves a chemical reaction, and reagents and conditions for each of these reactions need to be designed to give a good yield and a pure product, with as little work as possible[3]. A method may already exist in the literature for making one of the early synthetic intermediates, and this method will usually be used rather than "trying to reinvent the wheel". However most intermediates are compounds that have never been made before, and these will normally be made using general methods developed by methodology researchers. To be useful, these methods need to give high yields and to be reliable for a broad range of substrates. Methodology research usually involves three main stages- discovery, optimisation, and studies of scope and limitations. The discovery requires extensive knowledge of and experience with chemical reactivities of appropriate reagents. Optimisation is where one or two starting compounds are tested in the reaction under a wide variety of conditions of temperature, solvent, reaction time, etc., until the optimum conditions for product yield and purity are found. Then the researcher tries to extend the method to a broad range of different starting materials, to find the scope and limitations. Some larger research groups may then perform a total synthesis (see above) to showcase the new methodology and demonstrate its value in a real application.
Asymmetric synthesis
Many complex natural products occur as one pure enantiomer. Traditionally, however, a total synthesis could only make a complex molecule as a racemic mixture, i.e., as an equal mixture of both possible enantiomer forms. The racemic mixture might then be separated via chiral resolution.
In the latter half of the twentieth century, chemists began to develop methods of asymmetric catalysis and kinetic resolution whereby reactions could be directed to produce only one enantiomer rather than a racemic mixture. Early examples include Sharpless epoxidation (K. Barry Sharpless) and asymmetric hydrogenation (William S. Knowles and Ryoji Noyori), and these workers went on to share the Nobel Prize in Chemistry in 2001 for their discoveries. Such reactions gave chemists a much wider choice of enantiomerically pure molecules to start from, where previously only natural starting materials could be used. Using techniques pioneered by Robert B. Woodward and new developments in synthetic methodology, chemists became more able to take simple molecules through to more complex molecules without unwanted racemisation, by understanding stereocontrol. This allowed the final target molecule to be synthesised as one pure enantiomer without any resolution being necessary. Such techniques are referred to as asymmetric synthesis.
Synthesis design
Elias James Corey brought a more formal approach to synthesis design, based on retrosynthetic analysis, for which he won the Nobel Prize for Chemistry in 1990. In this approach, the research is planned backwards from the product, using standard rules[4]. The steps are shown using retrosynthetic arrows (drawn as =>), which in effect means "is made from". Other workers in this area include one of the pioneers of computational chemistry, James B. Hendrickson, who developed a computer program for designing a synthesis based on sequences of generic "half-reactions". Computer-aided methods have recently been reviewed.[5]
See also
- Organic Syntheses, a publication which gives detailed peer-tested laboratory procedures.
- Methods in Organic Synthesis, a journal
References
- ↑ Nicolaou, K. C.; Sorensen, E. J. (1996). Classics in Total Synthesis. New York: VCH.
- ↑ Woodward, R. B.; Cava, M. P.; Ollis, W. D.; Hunger, A.; Daeniker, H. U.; Schenker, K. (1954). "The Total Synthesis of Strychnine" (PDF subscription required). Journal of the American Chemical Society 76 (18): 4749–4751. doi:10.1021/ja01647a088.
- ↑ March, J.; Smith, D. (2001). Advanced Organic Chemistry, 5th ed. New York: Wiley.
- ↑ Corey, E. J.; Cheng, X-M. (1995). The Logic of Chemical Synthesis. New York: Wiley.
- ↑ Todd, Matthew H. (2005). "Computer-aided Organic Synthesis". Chemical Society Reviews 34: 247–266. doi:10.1039/b104620a.
External links
- Chemical synthesis database
- http://www.webreactions.net/search.html
- http://www.organic-chemistry.org/synthesis/
- Natural product syntheses
- Organic Chemistry Synthesis Approach and Modern Development
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This page was originally imported from Wikipedia, specifically this version of the article "Organic synthesis". Please see the history page on Wikipedia for the original authors. This WikiChem article may have been modified since it was imported. It is licensed under the Creative Commons Attribution–Share Alike 3.0 Unported license. |
