{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T09:39:19Z","timestamp":1770111559206,"version":"3.49.0"},"reference-count":37,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100005057","name":"National Tsing Hua University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"Taiwan Ministry of Science and Technology","doi-asserted-by":"publisher","award":["111-2320-B-400-008-MY3"],"award-info":[{"award-number":["111-2320-B-400-008-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"Taiwan Ministry of Science and Technology","doi-asserted-by":"publisher","award":["112-2320-B-400-015-MY3"],"award-info":[{"award-number":["112-2320-B-400-015-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024990","name":"National Yang Ming Chiao Tung University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100024990","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.bioorg.2026.109491","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T16:20:19Z","timestamp":1768234819000},"page":"109491","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Ruthenium(II)-catalyzed asymmetric transfer hydrogenation for enantioselective synthesis of (S)-\/(R)-4-ethyl-N-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]benzamide exhibiting differing antinociceptive effects"],"prefix":"10.1016","volume":"170","author":[{"given":"Sudhakar Dattatray","family":"Tanpure","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Chiao","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiao-Fu","family":"Chang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiu-Hwa","family":"Yeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shau-Hua","family":"Ueng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bioorg.2026.109491_bb0005","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1016\/S0960-894X(03)00583-3","article-title":"Neuroprotective or neurotoxic activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline and related compounds","volume":"13","author":"Okuda","year":"2003","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2026.109491_bb0010","doi-asserted-by":"crossref","first-page":"3207","DOI":"10.1039\/C6OB00253F","article-title":"BF3\u00b7OEt2 mediated metal-free one-pot sequential multiple annulation cascade (SMAC) synthesis of complex and diverse tetrahydroisoquinoline fused hybrid molecules","volume":"14","author":"Shinde","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"10.1016\/j.bioorg.2026.109491_bb0015","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.ejmech.2016.09.003","article-title":"Discovery, structure-activity relationship studies, and anti-nociceptive effects of N-(1,2,3,4-tetrahydro-1-isoquinolinylmethyl)benzamides as novel opioid receptor agonists","volume":"126","author":"Chen","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2026.109491_bb0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2019.107678","article-title":"BPR1M97, a dual mu opioid receptor\/nociceptin-orphanin FQ peptide receptor agonist, produces potent antinociceptive effects with safer properties than morphine","volume":"166","author":"Chao","year":"2020","journal-title":"Neuropharm"},{"key":"10.1016\/j.bioorg.2026.109491_bb0025","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1002\/adsc.200900719","article-title":"Chiral amine synthesis \u2013 recent developments and trends for enamide reduction, reductive amination, and imine reduction","volume":"352","author":"Nugent","year":"2010","journal-title":"Adv. Synth. Catal."},{"key":"10.1016\/j.bioorg.2026.109491_bb0030","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1039\/C5CC06712J","article-title":"Enantioselective hydrogenation of cyclic imines catalysed by Noyori\u2013Ikariya half-sandwich complexes and their analogues","volume":"52","author":"Vilhanova","year":"2016","journal-title":"Chem. Commun."},{"key":"10.1016\/j.bioorg.2026.109491_bb0035","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/adsc.200390011","article-title":"Enantioselective hydrogenation of imines using a diverse library of ruthenium dichloride(diphosphine)(diamine) precatalysts","volume":"345","author":"Cobley","year":"2003","journal-title":"Adv. Synth. Catal."},{"key":"10.1016\/j.bioorg.2026.109491_bb0040","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1021\/cr980414z","article-title":"Catalytic enantioselective addition to imines","volume":"99","author":"Kobayashi","year":"1999","journal-title":"Chem. Rev."},{"key":"10.1016\/j.bioorg.2026.109491_bb0045","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1021\/bi801443g","article-title":"Ligand-specific conformation determines agonist activation and antagonist blockade in purified human thromboxane A2 receptor","volume":"48","author":"Ruan","year":"2009","journal-title":"Biochemistry"},{"key":"10.1016\/j.bioorg.2026.109491_bb0050","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.cell.2016.09.021","article-title":"Ligand-dependent modulation of G protein conformation alters drug efficacy","volume":"167","author":"Furness","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.bioorg.2026.109491_bb0055","doi-asserted-by":"crossref","first-page":"3696","DOI":"10.1021\/acs.jcim.1c00585","article-title":"Delineating the ligand\u2212receptor interactions that lead to biased signaling at the \u03bc-opioid receptor","volume":"61","author":"Kelly","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.bioorg.2026.109491_bb0060","doi-asserted-by":"crossref","first-page":"6322","DOI":"10.1073\/pnas.97.12.6322","article-title":"Enantiomer discrimination illustrated by high-resolution crystal structures of the human nuclear receptor hRAR\u03b3","volume":"97","author":"Klaholz","year":"2000","journal-title":"Proc. Nal. Acad. Sci."},{"key":"10.1016\/j.bioorg.2026.109491_bb0065","doi-asserted-by":"crossref","first-page":"22279","DOI":"10.1038\/s41598-020-79251-9","article-title":"Enantiomer-specific activities of an LRH-1 and SF-1 dual agonist","volume":"10","author":"Mays","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2026.109491_bb0070","doi-asserted-by":"crossref","first-page":"7562","DOI":"10.1021\/ja00133a037","article-title":"Asymmetric transfer hydrogenation of aromatic ketones catalyzed by chiral ruthenium(II) complexes","volume":"117","author":"Hashiguchi","year":"1995","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.bioorg.2026.109491_bb0075","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1021\/ar9502341","article-title":"Asymmetric transfer hydrogenation catalyzed by chiral ruthenium complexes","volume":"30","author":"Hashiguchi","year":"1997","journal-title":"Acc. Chem. Res."},{"key":"10.1016\/j.bioorg.2026.109491_bb0080","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1021\/acs.orglett.5b00889","article-title":"Asymmetric transfer hydrogenation of imines in water by varying the ratio of formic acid to triethylamine","volume":"17","author":"Shende","year":"2015","journal-title":"Org. Lett."},{"key":"10.1016\/j.bioorg.2026.109491_bb0085","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1021\/ol802801p","article-title":"Ru(II) complexes of N-alkylated TsDPEN ligands in asymmetric transfer hydrogenation of ketones and imines","volume":"11","author":"Martins","year":"2009","journal-title":"Org. Lett."},{"key":"10.1016\/j.bioorg.2026.109491_bb0090","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1021\/ar700134q","article-title":"Asymmetric transfer hydrogenation of ketones with bifunctional transition metal-based molecular catalysts","volume":"40","author":"Ikariya","year":"2007","journal-title":"Acc. Chem. Res."},{"key":"10.1016\/j.bioorg.2026.109491_bb0095","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1039\/B513396C","article-title":"Asymmetric transfer hydrogenation: chiral ligands and applications","volume":"35","author":"Gladiali","year":"2006","journal-title":"Chem. Soc. Rev."},{"key":"10.1016\/j.bioorg.2026.109491_bb0100","doi-asserted-by":"crossref","first-page":"4373","DOI":"10.1021\/ol020213o","article-title":"Practical synthesis of optically active styrene oxides via reductive transformation of 2-chloroacetophenones with chiral rhodium catalysts","volume":"4","author":"Hamada","year":"2002","journal-title":"Org. Lett."},{"key":"10.1016\/j.bioorg.2026.109491_bb0105","doi-asserted-by":"crossref","first-page":"7391","DOI":"10.1021\/jo0491455","article-title":"Asymmetric transfer hydrogenation of \u03b1-aminoalkyl \u03b1\u2018-chloromethyl ketones with chiral Rh complexes","volume":"69","author":"Hamada","year":"2004","journal-title":"J. Organomet. Chem."},{"key":"10.1016\/j.bioorg.2026.109491_bb0110","article-title":"A remarkably effective catalyst for the asymmetric transfer hydrogenation of aromatic ketones in water and air","volume":"44474449","author":"Wu","year":"2005","journal-title":"Chem. Commun."},{"key":"10.1016\/j.bioorg.2026.109491_bb0115","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1021\/ol990098q","article-title":"A chiral rhodium complex for rapid asymmetric transfer hydrogenation of imines with high enantioselectivity","volume":"1","author":"Mao","year":"1999","journal-title":"Org. Lett."},{"key":"10.1016\/j.bioorg.2026.109491_bb0120","doi-asserted-by":"crossref","first-page":"16641","DOI":"10.1021\/acs.joc.1c01925","article-title":"Iridium-catalyzed asymmetric transfer hydrogenation of quinolines in biphasic systems or water","volume":"86","author":"Wang","year":"2021","journal-title":"J. Organomet. Chem."},{"key":"10.1016\/j.bioorg.2026.109491_bb0125","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1002\/chem.200701258","article-title":"RhIII- and IrIII-catalyzed asymmetric transfer hydrogenation of ketones in water","volume":"14","author":"Wu","year":"2008","journal-title":"Chem. Eur. J."},{"key":"10.1016\/j.bioorg.2026.109491_bb0130","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.tetasy.2006.04.023","article-title":"Enantioselective Synthesis of (R)-(\u2212)-Praziquantel (PZQ)","volume":"vol. 17","author":"Roszkowski","year":"2006","journal-title":"Tetrahedron Asymmetry"},{"key":"10.1016\/j.bioorg.2026.109491_bb0135","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/j.tetasy.2013.04.010","article-title":"Synthesis of New Mono-N-Tosylated Diamine Ligands Based on (R)-(+)-Limonene and their Application in Asymmetric Transfer Hydrogenation of Ketones and Imines","volume":"vol. 24","author":"Maurin","year":"2013","journal-title":"Tetrahedron Asymmetry"},{"key":"10.1016\/j.bioorg.2026.109491_bb0140","series-title":"CCDC 2493004 (S1) contain the supplementary crystallographic data for this paper","year":"2026"},{"key":"10.1016\/j.bioorg.2026.109491_bb0145","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0091-3057(84)90142-4","article-title":"The up-and-down method for the determination of nociceptive thresholds in rats","volume":"21","author":"Crocker","year":"1984","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.bioorg.2026.109491_bb0150","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2020.112290","article-title":"hERG toxicity assessment: useful guidelines for drug design","volume":"195","author":"Garrido","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.bioorg.2026.109491_bb0155","doi-asserted-by":"crossref","first-page":"8641","DOI":"10.1021\/acs.orglett.9b03251","article-title":"Josiphos-type binaphane ligands for iridium-catalyzed enantioselective hydrogenation of 1-aryl-substituted dihydroisoquinolines","volume":"21","author":"Nie","year":"2019","journal-title":"Org. Lett."},{"key":"10.1016\/j.bioorg.2026.109491_bb0160","doi-asserted-by":"crossref","first-page":"13649","DOI":"10.1021\/acscatal.1c03636","article-title":"Does the configuration at the metal matter in Noyori\u2212Ikariya type asymmetric transfer hydrogenation catalysts?","volume":"11","author":"Hall","year":"2021","journal-title":"ACS Catal."},{"key":"10.1016\/j.bioorg.2026.109491_bb0165","doi-asserted-by":"crossref","first-page":"5174","DOI":"10.1039\/c3dt32733g","article-title":"New insight into the role of a base in the mechanism of imine transfer hydrogenation on a Ru(II) half-sandwich complex","volume":"42","author":"Kuzma","year":"2013","journal-title":"Dalton Trans."},{"key":"10.1016\/j.bioorg.2026.109491_bb0170","doi-asserted-by":"crossref","first-page":"10679","DOI":"10.1002\/anie.201104476","article-title":"A highly efficient and enantioselective access to tetrahydroisoquinoline alkaloids: asymmetric hydrogenation with an iridium catalyst","volume":"50","author":"Chang","year":"2011","journal-title":"Angew. Chem. Int. Ed."},{"key":"10.1016\/j.bioorg.2026.109491_bb0175","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.6023\/cjoc202311027","article-title":"Design, synthesis and biological activity studies of 2-(1,3-dioxoiso-indolin-2-yl)-N-phenethylacetamide and 2-(3,4-dihydroisoquinolin-1-yl)isoindole-1,3-dione as monoamine oxidase (MAO) and cholinesterase (ChE) inhibitors","volume":"44","author":"Yiming","year":"2024","journal-title":"Chin. J. Org. Chem."},{"key":"10.1016\/j.bioorg.2026.109491_bb0180","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1021\/acs.orglett.4c00409","article-title":"Spiro-Josiphos ligands for the Ir-catalyzed asymmetric synthesis of chiral amines under hydrogenation conditions","volume":"26","author":"Li","year":"2024","journal-title":"Org. Lett."},{"key":"10.1016\/j.bioorg.2026.109491_bb0185","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114728","article-title":"Benzo[b]thiophene-2-carboxamides as novel opioid receptor agonists with potent analgesic effect and reduced constipation","volume":"243","author":"Kuppusamy","year":"2022","journal-title":"Eur. J. Med. Chem."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206826000271?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206826000271?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:20:26Z","timestamp":1770067226000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206826000271"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":37,"alternative-id":["S0045206826000271"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2026.109491","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ruthenium(II)-catalyzed asymmetric transfer hydrogenation for enantioselective synthesis of (S)-\/(R)-4-ethyl-N-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]benzamide exhibiting differing antinociceptive effects","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2026.109491","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"109491"}}