{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:18:51Z","timestamp":1790317131576,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"35","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21H02608"],"award-info":[{"award-number":["JP21H02608"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K18174"],"award-info":[{"award-number":["JP23K18174"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21J20696"],"award-info":[{"award-number":["JP21J20696"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2024,6,20]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There are many indole alkaloids that contain diverse functional groups attached to the benzene ring on the indole core. Promising biological activities of these alkaloids have been reported. Herein, we report the indole C5\u2010selective bromination of indolo[2,3\u2010<jats:italic>a<\/jats:italic>]quinolizidine alkaloids by adding nearly equimolar amounts of Br<jats:sub>3<\/jats:sub>\u2009\u22c5\u2009PyH and HCl in MeOH. The resulting reaction plausibly proceeds through an indoline intermediate by the nucleophilic addition of MeOH to the C3\u2010brominated indolenine intermediate. Data support the intermediacy of a C3\u2010, C5\u2010dibrominated indolenine intermediate as a brominating agent. These conditions demonstrate excellent selectivity for indole C5 bromination of natural products and their derivatives. Thus, these simple, mild, and metal\u2010free conditions allow for selective, late\u2010stage bromination followed by further chemical modifications. The utility of the brominated product prepared from naturally occurring yohimbine was demonstrated through various derivatizations, including a bioinspired heterodimerization reaction.<\/jats:p>","DOI":"10.1002\/chem.202401153","type":"journal-article","created":{"date-parts":[[2024,4,7]],"date-time":"2024-04-07T22:19:05Z","timestamp":1712528345000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Indole C5\u2010Selective Bromination of Indolo[2,3\u2010<i>a<\/i>]quinolizidine Alkaloids via In Situ\u2010Generated Indoline Intermediate"],"prefix":"10.1002","volume":"30","author":[{"given":"Go","family":"Yoshimura","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Chiba University  1-8-1, Inohana, Chuo-ku 260-8675 Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jukiya","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Chiba University  1-8-1, Inohana, Chuo-ku 260-8675 Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariko","family":"Kitajima","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Chiba University  1-8-1, Inohana, Chuo-ku 260-8675 Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3884-2583","authenticated-orcid":false,"given":"Hayato","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences Chiba University  1-8-1, Inohana, Chuo-ku 260-8675 Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"\u00a0"},{"key":"e_1_2_8_2_2","volume-title":"Introduction to Alkaloids: A Biogenetic Approach","author":"Cordell G. A.","year":"1981"},{"key":"e_1_2_8_3_2","volume-title":"The Alkaloids: Chemical and Biological Perspectives, Vol.\u20051","author":"Pelletier S. W.","year":"1983"},{"key":"e_1_2_8_4_2","volume-title":"Indoles and Biogenetically Related Alkaloids","author":"Phillipson J. D.","year":"1980"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/9780470186954"},{"key":"e_1_2_8_6_2","volume-title":"The Chemistry of Heterocyclic Compounds, Supplement to Volume\u200525, Part\u20054, The Monoterpenoid Indole Alkaloids","author":"Saxton J. E.","year":"1994"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1039\/np9971400559"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1039\/a707500f"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.890"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1039\/b512615k"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-chembioeng-061010-114209"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytol.2014.06.015"},{"key":"e_1_2_8_13_1","unstructured":"\u00a0"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2012.04.029"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115284"},{"key":"e_1_2_8_16_1","unstructured":"\u00a0"},{"key":"e_1_2_8_17_2","first-page":"1185","volume":"4","author":"Ata A.","year":"2009","journal-title":"Nat. Prod. Commun."},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2006-960052"},{"key":"e_1_2_8_19_1","unstructured":"\u00a0"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo1006762"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.03.104"},{"key":"e_1_2_8_22_1","unstructured":"\u00a0"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol0344772"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b07154"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b07154"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.0c00888"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol062173k"},{"key":"e_1_2_8_28_1","first-page":"421","author":"Johns S. R.","year":"1966","journal-title":"Chem. Commun."},{"key":"e_1_2_8_29_1","unstructured":"Deposition number 2337183 for3contains the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service."},{"key":"e_1_2_8_30_1","unstructured":"\u00a0"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo01344a023"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201200712"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2003.12.020"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(02)02193-7"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201600012"},{"key":"e_1_2_8_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/cjoc.201600344"},{"key":"e_1_2_8_37_1","unstructured":"\u00a0"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.19873200904"},{"key":"e_1_2_8_39_2","first-page":"1152","volume":"10","author":"Kubo M.","year":"1993","journal-title":"Chem. Soc. Jpn."},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.25.2350"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2862"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-9422(97)00513-X"},{"key":"e_1_2_8_43_1","unstructured":"\u00a0"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202104052"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202300179"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202005748"},{"key":"e_1_2_8_47_1","unstructured":"\u00a0"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00866a062"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)97675-5"},{"key":"e_1_2_8_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0957-4166(00)86273-4"},{"key":"e_1_2_8_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19960790510"},{"key":"e_1_2_8_52_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200300050"},{"key":"e_1_2_8_53_1","unstructured":"\u00a0"},{"key":"e_1_2_8_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(03)00739-1"},{"key":"e_1_2_8_55_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.6b00466"},{"key":"e_1_2_8_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b12800"},{"key":"e_1_2_8_57_1","unstructured":"\u00a0"},{"key":"e_1_2_8_58_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.7b01410"},{"key":"e_1_2_8_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202106184"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201602374"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1021\/np50091a014"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.2c02466"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.3987\/R-1982-04-0663"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.202200292"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo01284a028"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202401153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T18:40:30Z","timestamp":1760294430000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.202401153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":65,"journal-issue":{"issue":"35","published-print":{"date-parts":[[2024,6,20]]}},"alternative-id":["10.1002\/chem.202401153"],"URL":"https:\/\/doi.org\/10.1002\/chem.202401153","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,21]]},"assertion":[{"value":"2024-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202401153"}}