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Total synthesis
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In principle a total synthesis is the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes.
In practice, these simpler pieces are commercially available in bulk and semi-bulk quantites, and are often petrochemical precursors. Sometimes bulk natural products (e.g. sugars) are used as starting materials and it is assumed that these have or can be synthesised from their constituent elements.
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Encyclopedia
In principle a total synthesis is the complete chemical synthesis of complex organic molecules from simpler pieces, usually without the aid of biological processes.
In practice, these simpler pieces are commercially available in bulk and semi-bulk quantites, and are often petrochemical precursors. Sometimes bulk natural products (e.g. sugars) are used as starting materials and it is assumed that these have or can be synthesised from their constituent elements. The target molecules can be natural products, medicinally important active ingredients, or organic compounds of theoretical interest in chemistry or biology. A new route for synthesis is developed in the course of the investigation, and the route may be the first one to be developed for the substance.
The first demonstration of organic total synthesis was Friedrich Wöhler's synthesis of urea in 1828, which demonstrated that organic molecules can be produced from inorganic precursors, and the first commercialized total synthesis was Gustaf Komppa's synthesis and industrial production of camphor in 1903. Early efforts focused on building chemicals which were extracted from biological sources, and using them to verify their biological activities -- in this fashion, total synthesis was associated with disproving the existence of a vital force. As biology and chemistry became more sophisticated, the primary purpose for total synthesis changed, although some total synthesis continues to be a tool for biological verification, for example if a compound contains ambiguous stereochemistry or to create analogs ("chemical mutations") to directly assess or improve the mechanism of biological activity.
Today, total syntheses is often justified as a playground for the development of new chemical reactions and routes, and highlight the sophistication of modern synthetic organic chemistry. Sometimes total synthesis inspires the development of novel mechanisms, catalysts, or techniques. Finally since a total synthesis project will often span a variety of reactions, it serves to prepare chemists for pursuits in process chemistry, where encyclopedic knowledge of chemical reactions and a strong and accurate sense of chemical intuition are necessary.
Examples
Classical examples are the total syntheses of cholesterol, cortisone, strychnine, lysergic acid, reserpine, chlorophyll, colchicine, vitamin B12 and prostaglandin F-2a by the Nobel Prize winner Robert Burns Woodward between 1945 and 1976. Another classic is quinine total synthesis that has a history spanning 150 years. In some cases the structures of the molecules assigned by spectroscopic methods have been shown to be wrong, when synthesised.
Elias James Corey won the Nobel Prize in Chemistry in 1990 for lifetime achievement in total synthesis and the development of retrosynthetic analysis. In 2005 the group of Corey published an Aflatoxin total synthesis and in 2006 an oseltamivir total synthesis.
Among many groups who have made great strides in advancing the art and science of total synthesis, Kyriacos Costa Nicolaou at The Scripps Research Institute has also produced a number of review articles and books that highlight some of the accomplishments of the field. One example of his work is his contribution to Taxol total synthesis.
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