Project description
Novel chemical technology opens a new chapter in drug discovery
The cyclopropane ring is a chemical moiety that consists of three methylene groups joined together in a triangle. It is often introduced in small-molecule drugs at the early stages of synthesis to improve their metabolic stability, conformation and pharmacokinetics. The EU-funded LateCPC project aims to develop an innovative method that generates cyclopropanes from carbon-hydrogen bonds and can thus be exploited for the synthesis of complex drugs. Apart from expanding the applicability of the cyclopropane ring in medicinal chemistry, this method is expected to help address unmet medical needs through the discovery of novel drugs.
Objective
The cyclopropane ring is the 10th most commonly observed core in small-molecule drugs. This is due to the fact that cyclopropanes can positively influence metabolic stability, conformation, pKa, entropy, membrane permeability or pharmacokinetics in drug leads. The cyclopropane ring is often introduced in drug candidates at the early stages of the synthesis, however, the late-stage construction of multi-substituted cyclopropanes using C–H bonds as a functional group has not been developed yet. This concept promise to reach a “cyclopropanated” chemical space not possible by current strategies and that may impact how medicinal chemists will discover cyclopropane-based drugs that address unmet medical needs. LateCPC aims to develop an innovative technology to rapidly construct cyclopropanes from C–H bonds in feedstock and fine aromatic molecules as well as in complex drug molecules. Our approach will rely on the diazo activation of bespoke carbyne sources developed in the host group with metal catalysts, allowing the catalytic generation of metal-carbynoids. A key strength of this conceptually new and multidisciplinary proposal is the introduction of a secondment phase in Novartis (Basel) to explore real-life applications. The ambitious action merges perfectly the expertise of the host in novel C−H functionalization strategies based on the catalytic generation of innovative carbyne equivalents with the strong background of the applicant in metal-catalyzed Tsuji-Trost reactions, thus enhancing two-way transfer of knowledge between the ER and the host group. Successful development of this project will enable the ER to become a leader for the next generation in the field of chemical synthesis and late-stage functionalization techniques. The ER will be exposed to a wide range of cutting-edge chemistry and biomedical sciences in an interdisciplinary and international environment (ICIQ) that will aid the fellow’s competencies and cultivate him as independent researcher.
Fields of science
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Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
43007 Tarragona
Spain