|What is attractive aspect of natural products synthesis|
| Once you start the synthesis of natural products, you can not stop the synthesis, is the title of the talk of Prof. Keisuke Suzuki of TIT. The attractive ness of natural product synthesis is difficult to understand for the people who did study the synthesis of natural products. The attractiveness of natural product synthesis depends on the persons, because each person has different aspects of natural products synthesis. When you achieved total synthesis of natural product, you may get a sense of accomplishment, however the same feeling may be come from any other studies.
From my personal idea, the most attractive thing in the synthesis of natural product is the unpredictability, which may be founds as a common attractiveness among natural products chemistry. These are due to the diverse unique chemical structures that can not be imagined by human being. The diversity of natural products is the origin of biological activity, which could not be obtained by chemical library made by a conventional combinatorial synthesis. Studies on those natural products frequently encounter the unpredictable results.
In the case of natural products synthesis, unexpected reactivities encountered in the synthesis are attractiveness. Most of those cases, unexpected results are large interruption of the synthesis of natural products. When the intermediate structure is getting to be close to the target natural product, frequency of encountered unexpected reaction rapidly increased. Those include unusual reactivity by steric hindrance as well as neighbouring group interaction. Synthesis of multi-functional natural product provides us the good and valuable chance to know the different substrates shows the different reactivity under the identical conditions. To get forward the synthesis, you have to clarify the reason of the unexpected unique reactivity, and then control the reactivity. To do so, you should ask the compounds, that is try and error experiments as well as careful observation of your experiments. Since a simple but unexpected reactivity sometimes includes complicated reaction mechanism than you thought; what is essential is invisible to the eyes. However, to solve the difficulties as well as to control them is one of the attractive process in natural product synthesis.
In our laboratory, discovery of unpredicted reaction, clarification of the origin and the utilization of the reactions are the important as completion of the total synthesis of natural products. Unexpected reaction is usual troublemaker in the total synthesis, researcher who wants to synthesize the natural product used to tend to avoid the reaction. However, there are good chances to find the new reactions, new conditions, in some cases, the unpredicted reaction inspires us to find the new reactivity leading to the new synthetic plan of the natural product that you can not consider before. In the synthesis of specific compounds including natural products, truly efficient synthesis is not completed by simple combination of unit reactions with high generality, but by specific reaction which proceeds only in the specific substrates.
Therefore we now are going to synthesize small (Molecular weight up to 500) densely functionalized natural products, not only because of the interesting biological activity, but also increasing the possibility we encounter unexpected reaction in the synthesis.