{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Woo J"],"funding":["NIGMS NIH HHS"],"pagination":["77-82"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10907950"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["623(7985)"],"pubmed_abstract":["When searching for the ideal molecule to fill a particular functional role (for example, a medicine), the difference between success and failure can often come down to a single atom<sup>1</sup>. Replacing an aromatic carbon atom with a nitrogen atom would be enabling in the discovery of potential medicines<sup>2</sup>, but only indirect means exist to make such C-to-N transmutations, typically by parallel synthesis<sup>3</sup>. Here, we report a transformation that enables the direct conversion of a heteroaromatic carbon atom into a nitrogen atom, turning quinolines into quinazolines. Oxidative restructuring of the parent azaarene gives a ring-opened intermediate bearing electrophilic sites primed for ring reclosure and expulsion of a carbon-based leaving group. Such a 'sticky end' approach subverts existing atom insertion-deletion approaches and as a result avoids skeleton-rotation and substituent-perturbation pitfalls common in stepwise skeletal editing. We show a broad scope of quinolines and related azaarenes, all of which can be converted into the corresponding quinazolines by replacement of the C3 carbon with a nitrogen atom. Mechanistic experiments support the critical role of the activated intermediate and indicate a more general strategy for the development of C-to-N transmutation reactions."],"journal":["Nature"],"pubmed_title":["Carbon-to-nitrogen single-atom transmutation of azaarenes."],"pmcid":["PMC10907950"],"funding_grant_id":["R35 GM142768"],"pubmed_authors":["Levin MD","Christian AH","Stein C","Woo J"],"additional_accession":[]},"is_claimable":false,"name":"Carbon-to-nitrogen single-atom transmutation of azaarenes.","description":"When searching for the ideal molecule to fill a particular functional role (for example, a medicine), the difference between success and failure can often come down to a single atom<sup>1</sup>. Replacing an aromatic carbon atom with a nitrogen atom would be enabling in the discovery of potential medicines<sup>2</sup>, but only indirect means exist to make such C-to-N transmutations, typically by parallel synthesis<sup>3</sup>. Here, we report a transformation that enables the direct conversion of a heteroaromatic carbon atom into a nitrogen atom, turning quinolines into quinazolines. Oxidative restructuring of the parent azaarene gives a ring-opened intermediate bearing electrophilic sites primed for ring reclosure and expulsion of a carbon-based leaving group. Such a 'sticky end' approach subverts existing atom insertion-deletion approaches and as a result avoids skeleton-rotation and substituent-perturbation pitfalls common in stepwise skeletal editing. We show a broad scope of quinolines and related azaarenes, all of which can be converted into the corresponding quinazolines by replacement of the C3 carbon with a nitrogen atom. Mechanistic experiments support the critical role of the activated intermediate and indicate a more general strategy for the development of C-to-N transmutation reactions.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2025-04-26T17:07:15.293Z","creation":"2025-04-06T15:24:11.779Z"},"accession":"S-EPMC10907950","cross_references":{"pubmed":["37914946"],"doi":["10.1038/s41586-023-06613-4"]}}