Project description
Designing new heterocyclic rings for use in medicinal chemistry
Funded under the Marie Skłodowska-Curie Actions programme, the PHOTOLITH project plans to develop new photochemical reactions involving conjugated anions with lithium counterions (organolithiums and enolates). The goal is to construct functionalised, fused heterocyclic frameworks for use in medicinal chemistry. N-Allyl/N-benzyllithiums tethered to aromatic and heteroaromatic carboxamides will be employed in dearomatising cyclisations for constructing partially saturated fused ring systems and generating extended lithium enolates. Visible light radiation at a low temperature will induce a series of photochemical rearrangements, delivering demanding products in terms of structure that will contain various heterocycles and hetero-fused skeletons based on norcaradienes, cycloheptatrienes and cyclic ketones.
Objective
We propose to develop new photochemical reactions of conjugated anions with lithium counterions (organolithiums and enolates) to construct functionalized, fused heterocyclic frameworks of use in medicinal chemistry development. N-Allyl/N-benzyllithiums tethered to aromatic and heteroaromatic carboxamides will be employed in dearomatizing cyclizations for the construction of partially saturated fused ring systems, generating extended lithium enolates. Irradiation with visible light at low temperature will induce a series of photochemical rearrangements, delivering – in an operationally simple way - structurally demanding unusual products containing various heterocycles and hetero-fused skeletons based on norcaradienes, cycloheptatrienes, and cyclic ketones. Trapping the reactive cyclopropane units of the products with dipolarophiles such alkynes and olefins will extend the method to dearomatized polycycles via a [3+2] cycloaddition strategy. The method will then be extended from enolates to coloured, conjugated organolithiums more generally, promoting an electron from the HOMO (the C–Li bond of metalated carboxamides) to a new higher energy SOMO. This excited state takes the form of an anion-diradical which may be expected to undergo further interesting inter- or intramolecular reactions to furnish biologically relevant structures.
Fields of science
- natural scienceschemical sciencesorganic chemistryketones
- medical and health sciencesbasic medicinemedicinal chemistry
- natural scienceschemical sciencesinorganic chemistryalkali metals
- natural scienceschemical sciencesphysical chemistryphotochemistry
- natural scienceschemical sciencesorganic chemistryheterocyclic compounds
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
BS8 1QU Bristol
United Kingdom