{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T15:46:20Z","timestamp":1790783180991,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"65","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["17H06401, 19H02840, 22H04901, 23H04882, 24H00493"],"award-info":[{"award-number":["17H06401, 19H02840, 22H04901, 23H04882, 24H00493"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["22K05112"],"award-info":[{"award-number":["22K05112"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24ama221540h0001, 24ama121034j0003"],"award-info":[{"award-number":["24ama221540h0001, 24ama121034j0003"]}],"id":[{"id":"10.13039\/100009619","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":[[2024,11,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A robust, practical, and sustainable isomerization\u2010suppressed peptide bond formation via acyl sulfonamide, a twisted amide, is disclosed. Tosyl isocyanate and pentafluorobenzyl bromide were applied in combination to activate the peptide C\u2010terminus, which then reacted with an amine to yield an elongated peptide with high stereochemical purity. Careful analysis of NMR spectra of the active intermediate revealed the presence of an intramolecular hydrogen bond, suggesting that the hydrogen bond suppressed C\u03b1\u2010epimerization during amidation. The isomerization suppression by the intramolecular hydrogen bond is expected to be effective even under high dilution conditions, making the present method a powerful tool for the synthesis of complex macrocyclic peptides. In addition to peptide synthesis, the developed synthetic entry to twisted amides can be applied to the investigation of transition metal\u2010catalyzed N\u2212C bond activation. Moreover, the application to the N\u2212C bond activation returned insight into peptide synthesis, leading to the use of sulfonamide as a protecting group of carboxylic acid that can be orthogonally removed in the presence of other conventional protecting groups.<\/jats:p>","DOI":"10.1002\/chem.202403288","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T23:20:21Z","timestamp":1727479221000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Twisted Amide\u2010Mediated Peptide Synthesis"],"prefix":"10.1002","volume":"30","author":[{"given":"Ai","family":"Koyama","sequence":"first","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku, Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takefumi","family":"Kuranaga","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku, Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiki","family":"Suo","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku, Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryota","family":"Morimoto","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku, Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku, Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-7331","authenticated-orcid":false,"given":"Hideaki","family":"Kakeya","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku, Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,5]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr800323s"},{"key":"e_1_2_8_2_1","unstructured":"For examples see:"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14755-6"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41115-x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr100048w"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9637863"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.2c00005"},{"key":"e_1_2_8_8_1","unstructured":"For representative examples see:"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c00314"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42004-023-01030-0"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c02993"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c04614"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b03850"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201402147"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b07230"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202212247"},{"key":"e_1_2_8_17_1","unstructured":"One of the authors had experienced the structural confusion by NMR studies on highly isomerizable peptide that strongly motivated us to establish this work. See:"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b05550"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja401457h"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.0c00517"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.1c02506"},{"key":"e_1_2_8_22_1","unstructured":"\u00a0"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.0c02660"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-020-00400-3"},{"key":"e_1_2_8_25_1","unstructured":"\u00a0"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-022-04048-w"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1039\/D2AN01885C"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2024.124239"},{"key":"e_1_2_8_29_1","unstructured":"\u00a0"},{"key":"e_1_2_8_30_2","doi-asserted-by":"crossref","unstructured":"G.\u2005W. Kenner J.\u2005R. McDermott R.\u2005C. Sheppard J. Chem. Soc. D1971 636\u2013637;","DOI":"10.1039\/c29710000636"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9535165"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/cc0300255"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol0256320"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2006.11.143"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo01276a029"},{"key":"e_1_2_8_36_1","unstructured":"The 4-methoxyphenylacetyl group was attached to N-terminus of30for UV detection in the HPLC experiments to determine the isomerization ratio."},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol052351u"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00225"},{"key":"e_1_2_8_39_1","unstructured":"Alaninet-butyl ester is volatile and expensive compared to its hydrochloride salt. Therefore the hydrochloride salt (2 eq) was used with base (2 eq ofi-Pr2NEt) in the synthesis of35. On the other hand phenylalaninet-butyl ester is non-volatile and easy to handle."},{"key":"e_1_2_8_40_1","unstructured":"For examples of the alternative approaches via NMR study see:"},{"key":"e_1_2_8_41_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b04412"},{"key":"e_1_2_8_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.198205121"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.5b00769"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwv072"},{"key":"e_1_2_8_45_1","unstructured":"\u00a0"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja511743n"},{"key":"e_1_2_8_47_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5324.367"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00238a050"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00238a051"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201805541"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11418-022-01662-x"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1994.tb00393.x"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)72830-5"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.08.007"},{"key":"e_1_2_8_55_1","unstructured":"For examples see:"},{"key":"e_1_2_8_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c03710"},{"key":"e_1_2_8_57_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c08358"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.7b00249"},{"key":"e_1_2_8_59_1","unstructured":"For examples see:"},{"key":"e_1_2_8_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200351930"},{"key":"e_1_2_8_61_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201902866"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b13178"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202308251"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201605012"},{"key":"e_1_2_8_65_1","unstructured":"For representative examples see:"},{"key":"e_1_2_8_66_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14615"},{"key":"e_1_2_8_67_2","doi-asserted-by":"publisher","DOI":"10.1039\/C5CC00430F"},{"key":"e_1_2_8_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2388"},{"key":"e_1_2_8_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.6b03616"},{"key":"e_1_2_8_70_2","doi-asserted-by":"publisher","DOI":"10.1039\/C7SC02692G"},{"key":"e_1_2_8_71_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.9b01053"},{"key":"e_1_2_8_72_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.1c02183"},{"key":"e_1_2_8_73_2","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.2c05550"},{"key":"e_1_2_8_74_2","doi-asserted-by":"publisher","DOI":"10.1039\/D3SC05797F"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.2c01094"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00514a045"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)61830-0"},{"key":"e_1_2_8_78_1","unstructured":"It should be noted that all C\u03b1 epimers in this study were synthetically prepared as standard samples in HPLC and\/or NMR experiments. The stereochemical purity of the all resulting peptides were surely validated. See S86\u2013S101 in Supporting Information.."}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202403288","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T21:16:50Z","timestamp":1760303810000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.202403288"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,5]]},"references-count":78,"journal-issue":{"issue":"65","published-print":{"date-parts":[[2024,11,21]]}},"alternative-id":["10.1002\/chem.202403288"],"URL":"https:\/\/doi.org\/10.1002\/chem.202403288","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,5]]},"assertion":[{"value":"2024-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202403288"}}