{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T02:16:14Z","timestamp":1777774574214,"version":"3.51.4"},"reference-count":48,"publisher":"Wiley","issue":"51","license":[{"start":{"date-parts":[[2020,11,23]],"date-time":"2020-11-23T00:00:00Z","timestamp":1606089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2020,12,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>(\u2212)\u2010Finerenone is a nonsteroidal mineralocorticoid receptor antagonist currently in phase III clinical trials for the treatment of chronic kidney disease in type 2 diabetes. It contains an unusual dihydronaphthyridine core. We report a 6\u2010step synthesis of (\u2212)\u2010finerenone, which features an enantioselective partial transfer hydrogenation of a naphthyridine using a chiral phosphoric acid catalyst with a Hantzsch ester. The process is complicated by the fact that the naphthyridine exists as a mixture of two atropisomers that react at different rates and with different selectivities. The intrinsic kinetic resolution was converted into a kinetic dynamic resolution at elevated temperature, which enabled us to obtain (\u2212)\u2010finerenone in both high yield and high enantioselectivity. DFT calculations have revealed the origin of selectivity.<\/jats:p>","DOI":"10.1002\/anie.202011256","type":"journal-article","created":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T18:56:03Z","timestamp":1599332163000},"page":"23107-23111","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Enantioselective Total Synthesis of (\u2212)\u2010Finerenone Using Asymmetric Transfer Hydrogenation"],"prefix":"10.1002","volume":"59","author":[{"given":"Andreas","family":"Lerchen","sequence":"first","affiliation":[{"name":"School of Chemistry University of Bristol  Cantock's Close Bristol BS8 1TS UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narasimhulu","family":"Gandhamsetty","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Bristol  Cantock's Close Bristol BS8 1TS UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elliot H. E.","family":"Farrar","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Bath  Claverton Down Bath BA2 7AY UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"Winter","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Bristol  Cantock's Close Bristol BS8 1TS UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Platzek","sequence":"additional","affiliation":[{"name":"Chemical Development Bayer AG  42096 Wuppertal Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew N.","family":"Grayson","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Bath  Claverton Down Bath BA2 7AY UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0344-6430","authenticated-orcid":false,"given":"Varinder K.","family":"Aggarwal","sequence":"additional","affiliation":[{"name":"School of Chemistry University of Bristol  Cantock's Close Bristol BS8 1TS UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,23]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030207"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1009492"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.118.083337"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2011.06.025"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.199115591"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.19911031206"},{"key":"e_1_2_2_8_1","unstructured":"\u00a0"},{"key":"e_1_2_2_9_2","unstructured":"J.-K.Ergueden P.Kolkhof P.Sandner A.Kuhl J.-P.Stasch E.Pook K.-H.Schlemmer Int. Pat. Appl. WO2005\/087740 2005;"},{"key":"e_1_2_2_10_2","unstructured":"A.Kuhl P.Kolkhof H.Heckroth K.-H.Schlemmer I.Flamme S.Figueroa-Perez H.Gielen-Haertwig R.Grosser J.-K.Ergueden D.Lang US Pat. Appl. US20090214675 2009;"},{"key":"e_1_2_2_11_2","unstructured":"A.Kuhl P.Kolkhof H.Heckroth K.-H.Schlemmer I.Flamme S.Figueroa-Perez H.Gielen-Haertwig R.Grosser J.-K.Ergueden D.Lang US Pat. Appl. US20100022484 2010."},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201200081"},{"key":"e_1_2_2_13_1","unstructured":"J.Platzek K.Gottfried J.Assmann G.Lolli PCT Int. Appl. WO2017\/032678 2017."},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7OB00488E"},{"key":"e_1_2_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201604201"},{"key":"e_1_2_2_14_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201604201"},{"key":"e_1_2_2_15_1","unstructured":"\u00a0"},{"key":"e_1_2_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol5011196"},{"key":"e_1_2_2_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201106808"},{"key":"e_1_2_2_17_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201106808"},{"key":"e_1_2_2_18_1","unstructured":"For further approaches to generate 1 4-dihydroquinolines see:"},{"key":"e_1_2_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(99)01172-7"},{"key":"e_1_2_2_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201202161"},{"key":"e_1_2_2_20_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201202161"},{"key":"e_1_2_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo501406v"},{"key":"e_1_2_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.201401176"},{"key":"e_1_2_2_23_1","unstructured":"For selected reports on reductions using a chiral phosphoric acid in the presence organic hydrides see:"},{"key":"e_1_2_2_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1gc15027h"},{"key":"e_1_2_2_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol0515964"},{"key":"e_1_2_2_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200503062"},{"key":"e_1_2_2_26_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200503062"},{"key":"e_1_2_2_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja057222n"},{"key":"e_1_2_2_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200601832"},{"key":"e_1_2_2_28_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200601832"},{"key":"e_1_2_2_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200701158"},{"key":"e_1_2_2_29_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200701158"},{"key":"e_1_2_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200600191"},{"key":"e_1_2_2_30_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200600191"},{"key":"e_1_2_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/adsc.200800020"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm060465l"},{"key":"e_1_2_2_33_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-1982-29855"},{"key":"e_1_2_2_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2010.03.036"},{"key":"e_1_2_2_35_1","unstructured":"J.Platzek L.Zorn PCT Int. Appl. WO2017\/032627 2017."},{"key":"e_1_2_2_36_1","unstructured":"The absolute configuration of the two atropisomers has been determined by X-ray analysis and the CD spectra of both isomers have been reported (see Ref.\u2005[2] and [15]). We were able to compare the CD of the separated isomers to determine the absolute stereochemistry of the atropisomers."},{"key":"e_1_2_2_37_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1589532"},{"key":"e_1_2_2_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.8b02812"},{"key":"e_1_2_2_39_1","unstructured":"M.\u2005J. Frisch et\u2005al. Gaussian Inc. Wallingford CT Revision\u2009A.03.2016."}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202011256","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.202011256","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202011256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T05:47:15Z","timestamp":1693720035000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202011256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,23]]},"references-count":48,"journal-issue":{"issue":"51","published-print":{"date-parts":[[2020,12,14]]}},"alternative-id":["10.1002\/anie.202011256"],"URL":"https:\/\/doi.org\/10.1002\/anie.202011256","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,23]]},"assertion":[{"value":"2020-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-23","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}