{"doi":"10.1021/acsomega.5c07396","title":"A Green, Facile Method for Selective α-Bromination of Flavanones","abstract":"Flavonoids, a broad class of polyphenolic secondary metabolites, possess diverse and potent biological activities, including anti-inflammatory, antioxidative, antiviral, and analgesic properties. Flavanones, a prominent flavonoid subclass, are especially notable for their therapeutic potential, with several derivatives exhibiting anticancer and antiviral effects. Bromination is a valuable strategy in drug development, as halogenation can enhance biological activity and provide synthetic handles for further molecular elaboration. While aromatic bromination of flavonoids is known, selective α-bromination of flavanones, particularly those bearing hydroxy and alkoxy substituents, remains underexplored due to electronic and oxidative challenges. In this study, we investigated the selective α-bromination of hydroxy- and alkoxy-substituted flavanones, generating novel brominated derivatives. We identified a mild, green protocol for α-bromination of a range of monosubstituted flavanones in good yields using copper-(II) bromide in ethyl acetate. The α-bromination of flavanones bearing multiple hydroxyl groups resulted in poor selectivity and competing nuclear bromination, underscoring the challenges posed by increased aromatic nucleophilicity. Novel products were characterized using a combination of nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HRMS), tandem electrospray ionization mass spectrometry (ESI-MS/MS), and X-ray crystallography. These findings expand the chemical space of flavanone derivatives and provide valuable intermediates for the synthesis of pharmacologically relevant heterocycles.","journal":"ACS Omega","year":2025,"id":585531,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":600020,"name":"Tatiana N. Laremore","orcid":"0000-0002-1036-8963","position":1,"is_corresponding":false},{"id":792008,"name":"Hemant P. Yennawar","orcid":"0000-0003-2869-1109","position":2,"is_corresponding":false},{"id":832788,"name":"Gena D. Guerin","orcid":null,"position":3,"is_corresponding":false},{"id":1499358,"name":"Brendan Pelletier","orcid":null,"position":4,"is_corresponding":false},{"id":1499359,"name":"Samreen Dallal","orcid":null,"position":5,"is_corresponding":false},{"id":1499360,"name":"Sameer Aggroia","orcid":null,"position":6,"is_corresponding":false},{"id":1499361,"name":"Maria Englert","orcid":null,"position":7,"is_corresponding":false},{"id":688090,"name":"Christy George","orcid":"0000-0001-9210-2394","position":8,"is_corresponding":false},{"id":978309,"name":"Anna Sigmon","orcid":"0000-0001-8957-6193","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:59:20.067334Z","pmid":"41487166","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}