Abstract:
In this thesis the synthesis of diverse natural products is described. Most of the synthesized compounds belong to the polyketides, especially to the subclass of the benzolactones. The benzolactones are privileged structures, which means, that they show different biological activities, though they consist of a similar scaffolds.
In one chapter the concept of the propionate-scanning in benzolactones is described. Since the benzolactones (i. e. Zearalenone, Curvularin) are builded-up by several steps of a Claisen-condensation between acetates, the propionate-scanning looking forward to substitute an acetate with a propionate. With a propionate in the benzolactones there arise an additional stereocentre and an additional methyl group. Maybe this additional methyl group could have conformational effects and/or shows binding affinity to hydrophobic sites of proteins. The binding to the Hsp90 protein would be of high interest, because it is the aim of modern cancer therapy. Surprisingly, two compounds could be isolated, which show a higher binding activity to Hsp90 than Geldanamycin.
Additional to the polyketides, in the last years some alkaloids could be isolated which show the potential to be used in modern cancer-treatment. One of those is tyroscherin, which synthesis is described in one additional chapter. Tyroscherin shows a high and selective activity against IGF I MCF-7 human breast cancer cells with an IC50 of 9.3 ng/mL. The key-reactions to achieve the total synthesis of the natural products are a claisen-rearrangemant and a syn-Aldolreaction, followed by a Curtius-rearrangement.
Another important class of natural products are the carbohydrates. Among the carbohydrates, those of the L-row play a special role, because they are rarely found in nature and are mostly only subunits in complex natural products. Because of this, syntheses which have the sugars of the L-row as products are of high interest. During the synthesis of a natural product, the strategy to synthesise sugars of the L-row was developed. The key step in this sequence is an anti-aldolreaction, followed by an olefination, hydroboration and oxidations. The so obtained carbohydrate scaffolds could then be transformed to the final products, which are characterised by spectroscopic methods. With this strategy, a fast and short synthesis could be established, with which several carbohydrates could be obtained.