NATURAL PRODUCT

A natural product is a chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical drug discovery and drug design. A natural product can be considered as such even if it can be prepared by total synthesis.

Plants have always been a rich source of lead compounds (e.g. morphine, cocaine, digitalis, quinine, tubocurarine, nicotine, and muscarine). Many of these lead compounds are useful drugs in themselves (e.g. morphine and quinine), and others have been the basis for synthetic drugs (e.g. local anaesthetics developed from cocaine). Clinically useful drugs which have been recently isolated from plants include the anticancer agent paclitaxel (Taxol) from the yew tree, and the antimalarial agent artemisinin from Artemisia annua. Not all natural products can be fully synthesized and many natural products have very complex structures that are too difficult and expensive to synthesize on an industrial scale. These include drugs such as penicillin, morphine, and paclitaxel (Taxol). Such compounds can only be harvested from their natural source - a process which can be tedious, time consuming, and expensive, as well as being wasteful on the natural resource. For example, one yew tree would have to be cut down to extract enough paclitaxel from its bark for a single dose Furthermore, the number of structural analogues that can be obtained from harvesting is severely limited.

Semisynthetic procedures can sometimes get around these problems. This often involves harvesting a biosynthetic intermediate from the natural source, rather than the final (lead) compound itself. The intermediate could then be converted to the final product by conventional synthesis. This approach can have two advantages. First, the intermediate may be more easily extracted in higher yield than the final product itself. Second, it may allow the possibility of synthesizing analogues of the final product. The semisynthetic penicillins are an illustration of this approach. Another recent example is that of paclitaxel. It is manufactured by extracting 10-deacetylbaccatin III from the needles of the yew tree, then carrying out a four-stage synthesis.

Despite the potential limitations of natural products detailed above, these small molecules provide the source or inspiration for the majority of FDA-approved agents and continue to be one of the major sources of inspiration for drug discovery. In particular, these compounds are important in the treatment of life-threatening conditions. Pharmacognosy provides the tools to identify, select and process natural products destined for medicinal use. Usually, the natural product compound has some form of biological activity and that compound is known as the active principle - such a structure can act as a lead compound (not to be confused with compounds containing the element lead). Many of today's medicines are obtained directly from a natural source.