New late-stage functionalization reagents for the construction of chiral centers to impact drug discoveryhis her

Late-stage functionalization (LSF) is a rapidly expanding field in molecular synthesis with the major goal of quickly accessing to derivatives that would be too challenging or time-consuming to prepare otherwise; hence, this strategy has a great potential to impact drug discovery processes by speeding up the hit-to-lead optimization.

At present, more than two-thirds of prescription drugs contain at least one chiral center.

However, the late-stage introduction of this structural motif using aromatic C–H bonds is an enduring challenge in synthesis.

The goal of the NAKED-C project is to develop a new methodology for the construction of chiral centers in drug molecules, relying on the design and synthesis of a novel class of atomic carbon precursors that, upon successive and appropriate activations, would allow to build tailored asymmetric carbons.

To achieve this goal, a new visible-light photoredox catalytic diazomethylation of aromatic C–H bonds will be developed.

The collaboration with an industrial partner (secondment at AiCuris) will allow the application of this novel strategy to drug discovery in the search of effective antibiotics, thus merging multidisciplinary aspects with intersectoral knowledge transfer.

The result will be a brand-new ‘assembly point’ for the construction of chiral centers in bioactive compounds, with the potential to become a late-stage diversity-generating synthetic platform for drug discovery programs.

The proposal merges the host expertise in novel C−H functionalization strategies based on photocatalysis, and the researcher’s background in classical radical chemistry, metal-mediated synthesis and pharmacology, ensuring the two-way transfer of knowledge between the fellow and the host group.

Successful development of NAKED-C will enhance the scientific and transferable skills of the researcher, while forthcoming to the fellow’s professional goal of pursuing an independent research career in academia in synthetic organic chemistry.