Total synthesis

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. Syntheses may sometimes conclude at a precursor with further known synthetic pathways to a target molecule, in which case it is known as a formal synthesis. Total synthesis target molecules can be natural products, medicinally-important active ingredients, known intermediates, or molecules of theoretical interest. Total synthesis targets can also be organometallic or inorganic, though these are rarely encountered. Total synthesis projects often require a wide diversity of reactions and reagents, and subsequently requires broad chemical knowledge and training to be successful. Often, the aim is to discover a new route of synthesis for a target molecule for which there already exist known routes. Sometimes, however, no route exists, and chemists wish to find a viable route for the first time. Total synthesis is particularly important for the discovery of new chemical reactions and new chemical reagents, as well as establishing synthetic routes for medicinally important compounds. There are numerous classes of natural products for which total synthesis is applied to. These include (but are not limited to): terpenes, alkaloids, polyketides and polyethers. Total synthesis targets are sometimes referred to by their organismal origin such as plant, marine, and fungal. The term total synthesis is less frequently but still accurately applied to the synthesis of natural polypeptides and polynucleotides. The peptide hormones oxytocin and vasopressin were isolated and their total syntheses first reported in 1954. It is not uncommon for natural product targets to feature multiple structural components of several natural product classes. Although untrue from a historical perspective (see the history of the steroid, cortisone), total synthesis in the modern age has largely been an academic endeavor (in terms of manpower applied to problems).