Natural Product Chemistry

Prof. Dr. Thomas Lindel

Natural Products - Tools of Life

Why natural products?

If a compound is formed by a living organism, it is a natural product. This includes polymers and non-polymers. Natural products can be formed by particular organisms, such as the alkaloid morphine, or by all organisms, such as the nucleotides. Natural products are of prime importance for chemistry and for many neighboring disciplines such as biology and, further on, medicine. Biopolymers find many applications in material science. It is assumed that every natural product has been optimized by evolution towards a biological function, perhaps not alone, but as component of a mixture. For instance, nicotine acts as an insecticidal and protects the young plant. The key metabolite oroidin does the same for marine sponges. Other natural products serve the chemical communication among organisms, such as insect pheromones. Increasingly, the protein binding partners of natural products are being discovered. This promises to become a new El Dorado of natural product research.

Why natural product chemistry?

A natural product is a molecule that has to be treated and understood at atomic resolution. And it contains carbon, making it the subject of Organic Chemistry. Isolation and structure elucidation, partial and total synthesis, reactivity and functionalization stand at the heart of natural product chemistry. Chemistry is the only science that explores the full properties and dynamics associated with the electronic structure of a molecule. Natural products deserve it. Among natural products, one finds a structural complexity that surpasses that of other molecules. The skeletons of a natural product or even of advanced synthetic precursors may give rise to particular reactivities that would not be predicted by the presence of functional groups alone. This is fascinating for us as chemists and perhaps the true driving force behind natural product chemistry.

Why natural product synthesis?

The key goal of total synthesis, or target-oriented synthesis, is making a natural product available for interdisciplinary studies. Not every total synthesis really achieves that, because the final steps deal with single-digit milligram amounts that barely allow the determination of in vitro biological activities. However, as research progresses, total syntheses of interesting molecules become more and more elaborate, ideally (and never) leading to quantitative one-step processes starting from readily available starting materials. Thus, total synthesis frequently goes hand in hand with the development and testing of new synthetic steps that shorten existing sequences. The chemist is an architect. Total synthesis of natural products is also the main cause of structure revision, and the touchstone of synthetic methods.

There are natural product-based drugs being produced by total synthesis on the market. A recent example is the anticancer agent eribulin mesylate, an analog of the marine natural product halichondrin B, that is made industrially in a 62-step process with 34 steps in the longest linear sequence. Natural product synthesis may also start from precursors obtained by fermentation, as in the case of ecteinascidin 743 that is made from biologically produced cyanosafracin B by adding 18 synthetic steps.

Prof. Dr. Thomas Lindel

Curriculum vitae

TU Braunschweig
Institute of Organic Chemistry
Hagenring 30
38106 Braunschweig

phone int+49 531 391 7300
fax int+49 531 391 7744

Karin Dietz
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