Drug, sources chemical synthesis

Many clinically important pharmaceuticals and initial drug candidates are derived from natural sources such as microbes and plants (96). In most cases, the structural complexity of these drugs precludes chemical synthesis as a practical approach to commercially produce them. This consequently contributes to the dearth of derivatives of these compounds for evaluation as potential drug candidates. Also, slow generation time and low quantities of the drugs from their natural producers are usually major obstacles to contend with. 

An alternative to chemical synthesis is to use human CYP enzymes to generate the desired human drug metabolites. Various means of making human P450s have been used, all with certain drawbacks [81]. The most common source is pooled HLMs, which has been described in detail previously, but these microsomal preparations contain a mixture of many different enzymes, and their cost, batch-to-batch variability in activity and restrictions on availability can limit the usefulness of HLMs for preparative synthetic work. These limitations can become particularly acute when the required amount of a pure metabolite exceeds 5-10 mg. 

In addition to chemical-based drugs, a range of pharmaceutical substances (e.g. hormones and blood products) are produced by/extracted from biological sources. Such products, some major examples of which are listed in Table 1.2, may thus be described as products of biotechnology. In some instances, categorizing pharmaceuticals as products of biotechnology or chemical synthesis becomes somewhat artificial. For example, certain semi-synthetic antibiotics are produced by chemical modification of natural antibiotics produced by fermentation technology. 

Trace amounts of bromine in sodium diclofenac, sodium (2-[(2, 6-dichlorophenyl)amino] phenyl acetate, have been determined using XRF [82], since the drug substance should not contain more than 100 ppm of organic bromine remaining after the completion of the chemical synthesis. Pellets containing the analyte were compressed over a boric acid support, which yielded stable samples for analysis, and selected XRF spectra obtained in this study are shown in Fig. 7.19. It was found that samples from the Far East contained over 4000 ppm of organic bromine, various samples from Europe contained about 500 ppm, while samples from an Italian source contained less than 10 ppm of organic bromine. 

There are five basic sources of pharmaceuticals. By dollar value of products, fermentation is probably the most important, whereas by tonnage, chemical synthesis is dominant. Fermentation is used for antibiotics such as penicillins and tetracyclines. Chemical synthesis provides drugs such as the psychotropics and antihistamines. Animal extracts provide hormones. Biological sources lead to vaccines and serums. Vegetable extracts provide steroids and alkaloids. The top ten pharmaceutical companies in order of revenues are the following Merck, Pfizer, Bristol-Myers Squibb, Johnson ... 

Today, well over 100 drugs (accounting for 25% of all prescriptions issued in the USA), were initially isolated from vascular plants. While some are still extracted from their native source, most are now obtained more cheaply and easily by direct chemical synthesis or semi-synthesis. 

Liposomes are colloidal particles that can be prepared with (phospho)-lipid molecules derived from either natural sources or chemical synthesis (recently reviewed by Lian and Ho [14]). The potential application of liposomes as biodegradable or biocompatible drug carriers to enhance the potency and reduce the toxicity of therapeutic agents was recognized in 1960. In the 1960s and 1970s various methods for liposome preparation were developed as... 

Biodiversity New Leads for the Pharmaceutical and Agrochemical Industries reviews and discusses aspects of modern natural products research. The central theme of many articles is the sustainable use of global biodiversity. Microbial, plant and marine products are presented as the sources of new drugs, including anti-fungal products, antibiotics, anti-cancer agents and animal health products. There is also coverage of the biosynthesis of polyketides and the chemical synthesis of natural products and their derivatives. 

It is responsible for almost all heart drugs, drugs for the CNS, anti-ulcer drugs, analgesics and anti-histamines. Many pharmaceuticals are made simply from readily available bulk chemicals. For example, the non-steroid antiinflammatory agent, ibuprofen, is made from toluene and propylene, two of the seven basic building blocks of the petrochemical industry. Chemical synthesis is also used to modify materials made from other sources, and chemical methods of extraction are used in the downstream processing of products from other sources. 

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