Periodic Reporting for period 1 - CoSyMoDe (Cooperative Synthesis by Molecular Deconvolution)
Periodo di rendicontazione: 2022-01-01 al 2023-06-30
The CoSyMoDe action is entitles „Cooperative Synthesis by Molecular Deconvolution”. It addresses the lack of tools in Organic Synthesis to construct complex and intricate molecular structures – specifically small molecules – efficiently. In the usual case, the pursuit for a complex structure over-proportionally increases the synthetic affort required to access it synthetically. This inability of organic chemistry is strongly hampering the use of such complex e.g. 3-dimensional small molecules in pharmaceutical applications to date – leaving the better part of this industry with heterocyclic aromatic compounds to investigate. The latter compounds being flat (2-dimansional) and thus often lack selectivity when interacting with biological targets. The confinement to these 2-dimensional compunds strongly narrows down potential drug candidates and is slowing down chemical innovation in the field. The reason for the reluctance of pharmaceutical industry to carry out research on 3-dimensional complex molecules is the fact that synthetic complications get quickly in the way and require time, personnel and thus render the whole process unattractive due to mal ROIs (return of investments). As a consequence, industry deprives itself from target molecules that interact very selectively and specifically with biological targets – because 3-dimensional complex structures provide all these features making them ideal targets for pharmaceutical research. CoSyMode therefore addresses an important societal issue that obtained much public attention but prevailed for decades before already – the dependence of the EU on drug manufacturers of third party countries such as PR China and India. The pandemic and the months after that painfully brought this to light and urgently need to be solved. CoSyMoDe addresses this problem in so far as it provides an alternative to make 3-dimensional complex molecules efficiently accessible via organic chemistry and ease the use of their application for chemical industry. This will provide opportunities for innovation, new patents and lower the dependence of the EU on imports since an increased ROI allows companies to retain their manufacturing capacities within the EU were higher overall production costs prevail in comparison to the mentioned third-party countries.
The work performed in this reporting time involves the prove of concept which was accomplished in so far as the key reactions (fragmentation reactions) were successfully implemented.The taxane natural product family to which the the chemistry was applied is a well known natural product family and marketed since more than 30 years in cancer treatment. We were able to synthesize the most complex congener canataxpropellane andconvert the scaffold of this molecule into the backbones of the other family congeners. We are now dedicated to implement those findings to access the other taxane diterpene natural products efficiently to provide materialfor their pharmaceutical evaluation - a task previously impossible to accomplish due to lack of isolated material from natural sources.