The proposed research intends to develop a catalytic and environmentally-friendly approach for the rapid and simple construction of guanidine derivatives. Guanidines are of considerable pharmaceutical importance and some of their pharmaceutically interesting derivatives are generally difficult to construct using conventional synthetic methods. Application of mechanochemical methodologies allows the development of rapid and inherently low-solvent or even solvent-free synthetic methods, as previously demonstrated for pharmaceutical cocrystals and functional metal-organic materials. The recent discovery of catalytic effects in organic mechanosynthesis offers a suitable means to extend this efficiency, speed and versatility of mechanosynthesis into the broad field of organic synthesis. The proposed collaboration will take advantage of this opportunity and develop an environmentally-friendly synthetic approach of guanidine derivatives using Lewis acid catalysis. In order to achieve an efficient and green synthesis of guanidines, the research expertise of the Croatian group in guanidine chemistry with the expertise of the Cambridge team in the development of new approaches to conduct environmentally-friendly synthesis will be combined. Additionally, mechanochemistry will be used to screen for the binding of small molecules to guanidine derivatives. This will allow the study of their molecular recognition, important for understanding biological activity, in the absence of solvent and solubility effects that are inherent to all methodologies for studying molecular recognition to date. The ability to conduct mechanochemical processes in a high-throughput fashion will be an additional benefit that will enable the rapid optimisation of mechanochemical reaction conditions, screening for different types of Lewis acid catalysts, and construction of cocrystals. As Lewis acid catalysis is broadly applied across organic synthesis, we envisage that the realisation of this collaboration will open a vast number of new research directions in environmentally-friendly synthesis.

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