Total synthesis is the laboratory construction of a complex molecule, often a natural product, through a series of reactions using relatively simple and commercially available molecules as starting materials. In contrast, semisynthesis starts with larger molecules, also often from naturally occurring sources, with fewer reactions needed to reach the final product.
In its early days, total synthesis was used as a means of verifying chemical structures. As analytical chemistry progressed and chemical structures could be determined by instrumental analysis, researchers moved on to synthesizing complex molecules of biological, medicinal, or material importance. Today the emphasis in total synthesis is on what is sometimes called “ideal” synthesis: the efficient production of complex molecular structures in as few steps as possible. Step and atom economy are green chemistry; they improve synthetic efficiency by increasing yield and reducing waste and time. However, new reactions are needed to produce large quantities of molecules in a practical and environmentally friendly way. See also: Analytical chemistry; Atom economy; Bioorganic chemistry; Green chemistry
The basic steps of total synthesis are isolation, characterization, and a synthetic strategy. First a compound of interest (target molecule) must be isolated and characterized to determine its structure and functional properties (such as its pharmacological importance). To develop a synthetic strategy, investigators do a retrospective (retrosynthetic) analysis, working backward from the target molecule to identify a series of reactions that would produce it from the available starting materials. In constructing a retrosynthetic strategy, the analysis must consider the atoms, bonds, functional groups, conformational properties, and stereocenters of the target molecule. See also: Conformational analysis; Organic chemistry; Organic synthesis; Pharmacology; Stereochemistry
A classic example of a molecule derived from total synthesis is the monocyclic beta-lactam antibiotic aztreonam, a structurally modified compound originally isolated from Chromobacterium violaceum, a gram-negative rod-shaped bacterium. Aztreonam is produced synthetically and is used for treating infections with gram-negative bacteria. See also: Antibiotic; Bacteria