{"doi":"10.1021/acs.joc.3c01920","title":"Expedient Synthesis and Characterization of π-Extended Luciferins","abstract":"Bioluminescence imaging enables the sensitive tracking of cell populations and the visualization of biological processes in living systems. Bioluminescent luciferase/luciferin pairs with far-red and near-infrared emission benefit from the reduced competitive absorption by blood and tissue while also facilitating multiplexing strategies. Luciferins with extended π-systems, such as AkaLumine and recently reported CouLuc-1 and -3, can be used for bioluminescence imaging in this long wavelength regime. Existing synthetic routes to AkaLumine and similar π-extended compounds require a multistep sequence to install the thiazoline heterocycle. Here we detail the development of a two-step strategy for accessing these molecules via a Horner-Wadsworth-Emmons reaction and cysteine condensation sequence from readily available aldehyde starting materials. We detail an improved synthesis of AkaLumine, as well as the corresponding two-carbon homologues, Tri- and Tetra-AkaLumine. We then extended this approach to prepare coumarin- and naphthalene-derived luciferins. These putative luciferins were tested against a panel of luciferases to identify capable emitters. Of these, an easily prepared naphthalene derivative exhibits photon emission on par with that of the broadly used Akaluc/AkaLumine pair with similar emission maxima. Overall, this chemistry provides efficient access to several bioluminescent probes for a variety of imaging applications.","journal":"The Journal of Organic Chemistry","year":2023,"id":368433,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1033370,"name":"Katherine M. Townsend","orcid":"0000-0001-8004-0237","position":1,"is_corresponding":false},{"id":704002,"name":"Bethany Kolbaba‐Kartchner","orcid":"0000-0001-5004-1554","position":2,"is_corresponding":false},{"id":881811,"name":"Tanya Hadjian","orcid":"0000-0001-8194-4043","position":3,"is_corresponding":false},{"id":280791,"name":"Joseph Ivanic","orcid":"0000-0003-2104-7169","position":4,"is_corresponding":false},{"id":704001,"name":"Anna Love","orcid":"0000-0001-5657-2858","position":5,"is_corresponding":false},{"id":1126794,"name":"Beatrice Malvar","orcid":null,"position":6,"is_corresponding":false},{"id":704003,"name":"Jeremy H. Mills","orcid":"0000-0003-2017-1846","position":7,"is_corresponding":false},{"id":139834,"name":"Jennifer A. Prescher","orcid":"0000-0002-9250-4702","position":8,"is_corresponding":false},{"id":280793,"name":"Martin J. Schnermann","orcid":"0000-0002-0503-0116","position":9,"is_corresponding":false},{"id":671197,"name":"Donald R. Caldwell","orcid":"0000-0002-6023-3733","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T01:15:20.453499Z","pmid":"38096133","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":[]}