SulFourN2

The synthesis of bioactive compounds bearing unconventional functional groups and pharmacophores is a strategic task for pharmaceutical companies. In this context, the access to aza-analogues of sulfur derivatives is a great opportunity to obtain improved drug properties in terms of solubility, activity, target selectivity as well as patents expansion. The exploitation of emerging hexavalent sulfur functionalities has led to very conclusive results, as recently demonstrated by Bayer with the two drug candidates Roniciclib and Atuveciclib. Among the high valent sulfur derivatives, much less attention has been given to tetravalent sulfur, surely due to the lack of efficient synthetic methods. Even more surprising, the preparation of chiral sulfinamidines, the aza-anologues of sulfinamides, is distinctly underexplored. The preparation of chiral optically active sulfinamidines represents a highly valuable synthetic challenge, allowing the access to an unexplored chemical space. The enantioselective synthesis of such derivatives would allow for assessing their configurational stability in various chemical environments, open the route to further manipulations of the scaffolds, and address molecular diversity while preserving the sulfur configuration. In the SulFourN2 project, we will unlock the access to enantiopure sulfinamidines. Two distinct approaches will be tackled, combining the expertise of the three partners: the asymmetric addition of nucleophiles on sulfurdiimides and the asymmetric nitrogen transfer to sulfenamides. The sulfinamidines and their derivatives will be tested for their biological activities, and their physicochemical properties computationally assessed. It will bring additional knowledge and synthetic methods for their synthesis, ultimately allowing to explore their relative properties compare to other high valent sulfur analogues.