Total syntheses

Total synthesis is the complete chemical synthesis of a complex molecule, often a natural product, from simple, commercially available precursors. It usually refers to a process not involving the aid of biological processes, which distinguishes it from semisynthesis. The target molecules can be natural products, medicinally important active ingredients, or organic compounds of theoretical interest. Often the aim is to discover new route of synthesis for a target molecule for which there already exist known routes. Sometimes no route exists and the chemist wishes to find a viable route for the first time. One important purpose of total synthesis is the discovery of new chemical reactions and new chemical reagents.

The moniker of total synthesis is less frequently, but nevertheless accurately applied to the synthesis of natural polypeptides and polynucleotides; for instance, the peptide hormones and vasopressin were isolated, and their total syntheses first reported, in 1954.

Although untrue from a historical perspective (see the history of the steroid, cortisone) total synthesis in the modern age has largely been an academic endeavour (in terms of manpower applied to problems), although industrial concerns may pick up particular avenues of total synthesis efforts, and expend considerable resources on particular natural product targets, especially in cases where semi-synthesis can be applied to complex, natural product-derived drugs. Even so, there is continuing discussion regarding the value of total synthesis as an academic enterprise, some aspects of which are summarised here.

Total synthesis projects often require a variety of reactions, and so efforts to achieve complex total syntheses serve to prepare chemists for pursuits in pharmaceutical discovery chemistry, in particular, as well as in process chemistry, in both cases, where comprehensive knowledge of chemical reactions and a strong and accurate chemical intuition are important qualifications.

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