The search for novel drugs and new medicines strongly depends on the efficiency of synthetic processes. Especially in complex molecule synthesis the challenge to access a structure synthetically can be so huge and the effort so enormous, rendering the overall process inefficient.
In the quest for new medicines natural products are very often used, since they intrinsically are biologically active and give the medicinal chemist a head start. But natural product typically display a challenging three-dimensional structure - and thus are laborious to synthesise.
This has the consequence, that pharmaceutical companies stick to simple target molecules. The problem thereby is that simple structures only allow very crude design and thus the need for more selective and specific drugs cannot be met, since these properties most often are connected with a complex three-dimensional architecture. To overcome this process and make the quest for new bioactive compounds more efficient, we chose to develop a strategic approach called "artificial Natural product systems synthesis (ANaPSyS)". This concept aims to develop central building blocks that are structurally embedded in different natural products - so to say comprise a core structure - or as we like to call it "privileged intermediate". These building blocks are on the one hand advanced intermediates but at the same time can be flexibly used for different structure types of natural products. As a consequence such an intermediate is valuable not only for one specific target structure - as is normally the case in drug research - but can be used for multiple molecules with different biological activities. This inherently enhances synthetic efficiency and renders scale up process utmost important, since the privileged intermediate can be used multiple times, thus is needed in large quantities. We were able to put this concept into practice and showcase that this strategy is feasible by the synthesis of two different natural product family congeners with different biological activity (anti-jussive and hypotensive). The design of the privileged intermediate is thereby of utmost importance, and is developed with the help of intensive database search as was performed in our case.
