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.
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, four mature yew trees would have to be cut down to extract enough paclitaxel from their bark to treat one patient. Furthermore, the number of structural analogues that can be obtained from harvesting is severely limited.
A further problem is that isolates often work differently than the original natural products which have synergies and may combine, say, antimicrobial compounds with compounds that stimulate various pathways of the immune system: Many higher plants contain novel metabolites with antimicrobial and antiviral properties. However, in the developed world almost all clinically used chemotherapeutics have been produced by in vitro chemical synthesis. Exceptions, like taxol and vincristine, were structurally complex metabolites that were difficult to synthesize in vitro. Many non-natural, synthetic drugs cause severe side effects that were not acceptable except as treatments of last resort for terminal diseases such as cancer. The metabolites discovered in medicinal plants may avoid the side effect of synthetic drugs, because they must accumulate within living cells.
Semisynthetic procedures can sometimes get round 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.
