Natural products modern developments

These three prescriptions cover a span of nearly 2,500 years, but they have something fundamental in common They call for the use of natural products to cure illness. There have been relatively few times and few cultures in which natural products did not play a major role in the healing arts. Even today, in the highly modern world of the 21st century, extracts from plants and other organisms continue to he widely used in both developed and in developing nations. 

Also reactions that rapidly create more diversity are sought after. In recent years, more and more multicomponent reactions (MCRs) have been developed and combined with modern synthetic methods such as RCM or Pd couplings to provide rapid access to complex, natural product-like structures in solution. 

Medical applications of alkaloids have led to the production of drugs and drug components. They can be based on pure natural alkaloids, as in the case of extracts. Purified alkaloids, partially and even totally synthesized compounds based on the natural alkaloid structure, are also used. Chemically modified alkaloids are yet another example. Chemically modifying the structure affects biological activity. The general trend in modern medicine is to develop compounds that are biologically more active than those found in nature. This is achieved in many cases by alkaloid modifications and synthesis. However, natural compounds themselves are very important because they are the basis for artificial drugs. Moreover, alkaloids used as natural products are important... 

The number of synthetically produced fragrance and flavor chemicals has since expanded continually as a result of the systematic investigation of essential oils and fragrance complexes for odoriferous compounds. Initially, only major components were isolated from natural products their structure was then elucidated and processes were developed for their isolation or synthesis. With the development of modern analytical techniques, however, it became possible to isolate and identify... 

This case history presents only a simple account of one of R.B. Woodward s adventures based on ingenious understanding of structural features and experimental findings described in the literature. The hydrogenation of porphyrins is still one of the most active subjects in heterocyclic natural products chemistry, and the interested reader may find some modern developments in the publications of A. Eschenmoser (C.Angst, 1980 J.E. Johansen, 1980). 

The development of novel materials and the search for new bioactive compounds, such as natural products and analogues, drugs, diagnostics and agrochemicals, in academic and industrial chemistry is closely connected to the efficient preparation of such compounds. Thus, the view of synthesis has altered in recent years the development of new, highly selective methods will still be an important task, but the main focus of today s chemists is on efficiency [1], Multi-step syntheses with more than 20 steps have to be avoided since they are neither economically nor ecologically justifiable. Thus, modern syntheses must deal carefully with our resources and our time, must reduce the amount of waste formed, should use catalytic transformations and finally must avoid all toxic reagents and solvents. 

Shorter discovery timelines and accelerated development expectations have hindered the traditional approaches for natural products research. Furthermore, emphasis on chemical diversity presents a great challenge in this area, particularly because traditional natural products screening programs focus on one source of chemical diversity such as microorganisms or plants. Still, the primary issue remains how to assay this ideal source of new, biologically active compounds within the current timeframe necessary for modern drug discovery research. At the heart of this issue is the fact that traditional isolation and scale-up procedures are inefficient and often become the bottleneck in natural products dereplication. 

In natural product drug discovery, compound purification is an essential step in identifying a new chemical entity. In the modern HTS environment, speed is essential for natural products to compete with synthetics, efficient purification is vital to facilitate rapid structural elucidation of hits. Additionally, preparative purification strategies need to provide large quantities for a lead natural product to move forward in the development process. 

We promised to return to the earlier statement that a healthy development pipeline of natural product derived candidates implies that natural products will still have a role to play in modern day drug discovery. In fact, this is far from reality. Firstly, these late-stage clinical candidates reflect the output from research activities undertaken at least 10 years ago and certainly not the current situation. Secondly, there is a lack of truly novel chemical templates in the pipeline and thirdly, it is clear that very few pharmaceutical companies remain engaged, at least internally, in natural product drug discovery activities. 

Although the use of bioactive natural products as herbal drug preparations dates back hundreds, even thousands, of years ago, their application as isolated and characterized compounds to modern drug discovery and development only started in the 19th cenmry, the dawn of the chemotherapy era. It has been well documented that natural products played critical roles in modem dmg development, especially for antibacterial and antitumor agents. More importantly, natural products presented scientists with unique chemical stmctures, which are beyond human imagination most of the time, and inspired scientists to pursue new chemical entities with completely different stmctures from known dmgs. 

K. C., Petasis, N. A. In Selenium in Natural Product Synthesis, CIS Inc. Philadelphia, 1984. (c) Paulmier, C. In Selenium Reagents and Intermediates in Organic Synthesis, Pergamon Press Oxford, UK, 1986. (d) Liotta, D. Organoselenium Chemistry, Wiley New York, 1987. (e) Back, T. G. Organoselenium Chemisttj A Practiced Approach, Oxford University Press Oxford, UK, 1999. (f) Organoselenium Chemistry Modern Developments in Organic Synthesis,... 

---