In principle a total synthesis is the complete chemical synthesis of complex organic molecules from their constituent elements. In practice, simple, commercially available (often petrochemical) precursors or 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 products 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. Total syntheses are often used as a playground for the development of new chemical reactions and routes, and highlight the sophistication of modern synthetic organic chemistry. In universities, total synthesis also serves education.
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.
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. The first commercialized total synthesis was Gustaf Komppa's synthesis and industrial production of camphor in 1903.
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 (and are of great didactic utility if one should like to dig deeper into this fascinating and inspiring field). One example of his work is his contribution to Taxol total synthesis.
- K. C. Nicolaou, D. Vourloumis, N. Winssinger and P. S. Baran (2000). "The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century" (reprint). Angewandte Chemie International Edition 39 (1): 44-122. doi:10.1002/(SICI)1521-3773(20000103)39:1%3C44::AID-ANIE44%3E3.0.CO;2-L.
- Nicolaou, K. C.; Sorensen, E. J. Classics in Total Synthesis, 1996.
- Nicolaou, K. C.; Snyder, S. A. Classics in Total Synthesis II, 2003.
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