{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:13:39Z","timestamp":1792228419356,"version":"4.4.0"},"reference-count":34,"publisher":"Wiley","issue":"37","license":[{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T00:00:00Z","timestamp":1753488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM063557"],"award-info":[{"award-number":["GM063557"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL151125"],"award-info":[{"award-number":["HL151125"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014898","name":"ACS Division of Organic Chemistry","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014898","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006537","name":"Vanderbilt University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006537","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023581","name":"National Science Foundation Graduate Research Fellowship Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100023581","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":[[2025,9,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The preparation of peptidic molecules is a mainstay of synthesis, creating new tools that advance chemical biology, catalysis, and drug discovery. Despite the wide adoption of methods for amide synthesis based on electrophilic acyl transfer reactions, significant limitations remain that restrict access to chemical space and plague accessible peptides with imperfect conservation of stereochemical information. These problems persist in key applications (i.e., solid phase peptide synthesis) where reagent excess can be used to drive maximal yield. As a general tactic, however, use of excess coupling agents that are often hazardous is unsustainable. Here we report the synthesis of the antiviral tridecapeptide feglymycin where half of the amides are formed using umpolung amide synthesis (UmAS) to replace conventional amide synthesis. Reliance on UmAS further allowed the enantioselective synthesis of each noncanonical residue from an inexpensive aldehyde. As a result, the most process\u2010intensive components were simplified to a chiral Br\u00f8nsted acid organocatalyst and potassium iodide\/urea\u00b7hydrogen peroxide (KI\/UHP). This solution\u2010phase total synthesis illustrates the harmonious, strategic application of complementary amide synthesis methods, and it serves as a touchstone for the green synthesis of peptides composed of noncanonical amino amides.<\/jats:p>","DOI":"10.1002\/anie.202508819","type":"journal-article","created":{"date-parts":[[2025,7,26]],"date-time":"2025-07-26T13:14:29Z","timestamp":1753535669000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Total Synthesis of Feglymycin Using Umpolung Amide Synthesis"],"prefix":"10.1002","volume":"64","author":[{"given":"Preston C.","family":"Gourville","sequence":"first","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade A.","family":"Bing","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashanique D.","family":"Quarels","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey V.","family":"Tsukanov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth E.","family":"Schwieter","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuyuki","family":"Tokumaru","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda B.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn M.","family":"Makley","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail N.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0885-636X","authenticated-orcid":false,"given":"Jeffrey N.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Chemical Biology Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,26]]},"reference":[{"key":"e_1_2_5_1_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5NP00025D"},{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-3773(19990503)38:9<1172::AID-ANIE1172>3.0.CO;2-C"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/b402985m"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2017.08.006"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c03710"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.oprd.2c00005"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pep2.24210"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00237"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3SC01944F"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200804130"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13491"},{"key":"e_1_2_5_12_1","unstructured":"A brief summary of selected studies that approximate the degree of epimerization during aryl glycinamide is provided in the SI."},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09125"},{"key":"e_1_2_5_14_1","unstructured":"Abbreviations: D. (3\u2010(diethoxyphosphoryloxy)\u20101 2 3\u2010benzotriazin\u20104(3H)\u2010one); UHP (urea hydrogen peroxide); Hpg (4\u2010hydroxyphenyl glycine); Dpg (3 5\u2010dihydroxyphenyl glycine); (R R)\u2010PBAM (pyrrolidine bis(amidine) catalyst shown in Fig. 3A); EDC (1\u2010ethyl\u20103\u2010(3\u2010dimethylaminopropyl)carbodiimide\u22c5HCl); HOAt (1\u2010hydroxy\u20107\u2010azabenzotriazole)."},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113553108"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2019.03.001"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr00013a007"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10989-021-10308-7"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c07433"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4SC01081G"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.15227\/orgsyn.093.0088"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(97)00972-6"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1SC06133J"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.3c01494"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.9b03280"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/B703488C"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b08663"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.3c00037"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol990573k"},{"key":"e_1_2_5_30_1","unstructured":"p(BnO)C6H4CHO: $0.40\/g vs. Boc\u2010L\u2010Hpg: $6\/g Boc\u2010D\u2010Hpg: $7\/g (source: Combi\u2010Blocks)."},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24908-w"},{"key":"e_1_2_5_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c05986"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol8004276"},{"key":"e_1_2_5_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol501297a"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202508819","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202508819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T06:02:13Z","timestamp":1764482533000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202508819"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,26]]},"references-count":34,"journal-issue":{"issue":"37","published-print":{"date-parts":[[2025,9,8]]}},"alternative-id":["10.1002\/anie.202508819"],"URL":"https:\/\/doi.org\/10.1002\/anie.202508819","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,26]]},"assertion":[{"value":"2025-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202508819"}}