Natural product synthesis

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The synthesis of natural products is a branch of organic chemistry that deals with the development of efficient syntheses of naturally occurring substances, the natural substances , is concerned. The active ingredient target compounds ( targets ) are mostly substances that represent potential drugs and are intended to be used, for example, in cancer therapy .

Once a substance has been discovered that shows the desired pharmacological activity, the problem often arises that it can only be isolated in small quantities from natural sources. A well-known example is the extremely effective anti-tumor drug paclitaxel , which is obtained from the bark of the Pacific yew tree ( Taxus brevifolia ). The need for paclitaxel by far exceeds the amount that can be obtained from the trees, since the extraction can only take place by killing the tree and the trees also grow very slowly.

Synthetic routes

The task is to develop synthetic routes for substances such as paclitaxel that enable production on an industrial scale. The focus is on the efficiency of the synthesis. In this context, efficiency means u. a .:

  • as few steps as possible
  • Avoidance of by-products and the use of toxic reagents not approved for use in the manufacture of medicines
  • Inclusion of catalytic processes ( catalyst )
  • low financial outlay

In the case of paclitaxel, a competition broke out in the course of which several research groups developed a synthesis strategy. They pursued different approaches: on the one hand, the step-by-step construction of the molecule (linear synthesis), on the other hand, the separate construction of various more complex fragments of the molecule, which are then combined to form the active ingredient (convergent synthesis). These methods are so-called total syntheses , in which the molecule is assembled from simpler molecules.

There is also the possibility of partial synthesis , in which a structurally related substance is transformed into the substance sought in just a few steps. This approach is particularly useful when the structurally related material can be obtained in larger quantities from natural sources.

Optimizing the fabrics

The natural product synthesis also includes the optimization of the substances for the intended application. This is necessary, for example, if a substance shows unpleasant side effects in addition to the desired effect . In this case, the molecular cause of the side effects must be investigated so that they can be eliminated by modifying the structure. The challenge here is not to eliminate the desired effect with the side effects. At this point, natural product synthesis moves in the border area to medicine , pharmacology , pharmaceutical biology , biochemistry and related sciences.

Current research strives to understand the mechanisms of action and tries to establish a relationship between structure and effect of a substance so that in the future one can predict pharmacological activity and produce active substances in a targeted manner.

See also

literature

credentials

  • RA Holton, C. Somoza, HB Kim, F. Liang, RJ Biediger, PD Boatman, M. Shindo, CC Smith, S. Kim: First total synthesis of taxol. 1. Functionalization of the ring. In: J. Am. Chem. Soc. 116 (4), 1994, pp. 1597-1598. doi: 10.1021 / ja00083a066
  • KC Nicolaou, Z. Yang, JJ Liu, H. Ueno, PG Nantermet, RK Guy, DF Claiborne, J. Renaud, EA Couladouros, K. Paulvannan, EJ Sorensen: Total synthesis of taxol. In: Nature . 367, 1994, pp. 630-634. doi: 10.1038 / 367630a0
  • SJ Danishefsky, JJ Masters, WB Young, JT Link, LB Snyder, TV Magee, DK Jung, RCA Isaacs, WG Bornmann, CA Alaimo, CA Coburn, MJ Di Grandi: Total Synthesis of Baccatin III and Taxol. In: J. Am. Chem. Soc. 118 (12), 1996, pp. 2843-2859. doi: 10.1021 / ja952692a