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Organic synthesis is a special branch of
chemical synthesis As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In mod ...
and is concerned with the intentional construction of
organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...
s.
Organic Organic may refer to: * Organic, of or relating to an organism, a living entity * Organic, of or relating to an anatomical organ Chemistry * Organic matter, matter that has come from a once-living organism, is capable of decay or is the product ...
molecules are often more complex than inorganic compounds, and their synthesis has developed into one of the most important branches of
organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J ...
. There are several main areas of research within the general area of organic synthesis: '' total synthesis'', ''
semisynthesis Semisynthesis, or partial chemical synthesis, is a type of chemical synthesis that uses chemical compounds isolated from natural sources (such as microbial cell cultures or plant material) as the starting materials to produce novel compounds with ...
'', and ''
methodology In its most common sense, methodology is the study of research methods. However, the term can also refer to the methods themselves or to the philosophical discussion of associated background assumptions. A method is a structured procedure for br ...
''.


Total synthesis

A total synthesis is the complete
chemical synthesis As a topic of chemistry, chemical synthesis (or combination) is the artificial execution of chemical reactions to obtain one or several products. This occurs by physical and chemical manipulations usually involving one or more reactions. In mod ...
of complex
organic Organic may refer to: * Organic, of or relating to an organism, a living entity * Organic, of or relating to an anatomical organ Chemistry * Organic matter, matter that has come from a once-living organism, is capable of decay or is the product ...
molecule A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and b ...
s from simple, commercially available
petrochemical Petrochemicals (sometimes abbreviated as petchems) are the chemical products obtained from petroleum by refining. Some chemical compounds made from petroleum are also obtained from other fossil fuels, such as coal or natural gas, or renewabl ...
or
natural Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans ar ...
precursors. Total synthesis may be accomplished either via a linear or convergent approach. In a ''linear'' synthesis—often adequate for simple structures—several steps are performed one after another until the molecule is complete; the chemical compounds made in each step are called synthetic intermediates. Most often, each step in a synthesis refers to a separate reaction taking place to modify the starting compound. For more complex molecules, a convergent synthetic approach may be preferable, one that involves individual preparation of several "pieces" (key intermediates), which are then combined to form the desired product. Convergent synthesis has the advantage of generating higher yield, compared to linear synthesis. Robert Burns Woodward, who received the 1965 Nobel Prize for Chemistry for several total syntheses (e.g., his 1954 synthesis of
strychnine Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the e ...
), is regarded as the father of modern organic synthesis. Some latter-day examples include Wender's, Holton's, Nicolaou's, and Danishefsky's total syntheses of the anti-cancer therapeutic, paclitaxel (trade name, Taxol).


Methodology and applications

Each step of a synthesis involves a
chemical reaction A chemical reaction is a process that leads to the chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the positions of electrons in the forming and breaking ...
, and reagents and conditions for each of these reactions must be designed to give an adequate yield of pure product, with as few steps as possible. 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 an effort 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. For practical applications, additional hurdles include industrial standards of safety and purity. Methodology research usually involves three main stages: ''
discovery Discovery may refer to: * Discovery (observation), observing or finding something unknown * Discovery (fiction), a character's learning something unknown * Discovery (law), a process in courts of law relating to evidence Discovery, The Discove ...
'', '' optimisation'', and studies of ''scope and limitations''. The ''discovery'' requires extensive knowledge of and experience with chemical reactivities of appropriate reagents. ''Optimisation'' is a process in which one or two starting compounds are tested in the reaction under a wide variety of conditions of
temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer. Thermometers are calibrated in various temperature scales that historically have relied o ...
,
solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
, reaction time, etc., until the optimal conditions for product yield and purity are found. Finally, the researcher tries to extend the method to a broad range of different starting materials, to find the scope and limitations. Total syntheses (see above) are sometimes used to showcase the new methodology and demonstrate its value in a real-world application. Such applications involve major industries focused especially on polymers (and plastics) and pharmaceuticals. Some syntheses are feasible on a research or academic level, but not for industry level production. This may lead to further modification of the process.


Stereoselective synthesis

Most complex natural products are chiral, and the bioactivity of chiral molecules varies with the enantiomer. Historically, total syntheses targeted racemic mixtures, mixtures of both possible enantiomers, after which the racemic mixture might then be separated via chiral resolution. In the later half of the twentieth century, chemists began to develop methods of stereoselective
catalysis Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
and kinetic resolution whereby reactions could be directed to produce only one enantiomer rather than a racemic mixture. Early examples include stereoselective
hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...
s (e.g., as reported by William Knowles and
Ryōji Noyori is a Japanese chemist. He won the Nobel Prize in Chemistry in 2001, Noyori shared a half of the prize with William S. Knowles for the study of chirally catalyzed hydrogenations; the second half of the prize went to K. Barry Sharpless for his ...
, and functional group modifications such as the asymmetric epoxidation of
Barry Sharpless Karl Barry Sharpless (born April 28, 1941) is an American chemist and a two-time Nobel laureate in Chemistry known for his work on stereoselective reactions and click chemistry. Sharpless was awarded half of the 2001 Nobel Prize in Chemistry "f ...
; for these specific achievements, these workers were awarded the
Nobel Prize in Chemistry ) , image = Nobel Prize.png , alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
in 2001. 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 Robert Burns Woodward (April 10, 1917 – July 8, 1979) was an American organic chemist. He is considered by many to be the most preeminent synthetic organic chemist of the twentieth century, having made many key contributions to the subject, e ...
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, allowing final target molecules to be synthesised as pure enantiomers (i.e., without need for resolution). Such techniques are referred to as ''
stereoselective synthesis Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecu ...
''.


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 synthesis is planned backwards from the product, using standard rules. The steps "breaking down" the parent structure into achievable component parts are shown in a graphical scheme that uses ''retrosynthetic arrows'' (drawn as ⇒, which in effect, mean "is made from"). More recently, and less widely accepted, computer programs have been written for designing a synthesis based on sequences of generic "half-reactions".


See also

* ''
Organic Syntheses ''Organic Syntheses'' is a peer-reviewed scientific journal that was established in 1921. It publishes detailed and checked procedures for the synthesis of organic compounds. A unique feature of the review process is that all of the data and exp ...
'' (journal) * '' Methods in Organic Synthesis'' (journal) * Electrosynthesis * Automated Synthesis


References


Further reading

*


External links


The Organic Synthesis Archive

Chemical synthesis database
* https://web.archive.org/web/20070927231356/http://www.webreactions.net/search.html * https://www.organic-chemistry.org/synthesis/

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Chemical synthesis semantic wiki
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