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The final construction of the macrolactone core was based on a high\u2010yielding intramolecular HWE olefination, while the hemiaminal\u2010linked side chain was elaborated through a stereoselective, BINAL\u2010H\u2010mediated addition of (\n                    <jats:italic>Z,E<\/jats:italic>\n                    )\u2010sorbamide to a macrocyclic aldehyde precursor. The synthesis of the common functionalized morpholine building block involved two consecutive epoxide openings with tosylamide and the product of the first opening reaction, respectively, as nucleophiles. Of the three morpholino\u2010zampanolides investigated, the\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl and the\n                    <jats:italic>N<\/jats:italic>\n                    \u2010benzoyl derivatives both exhibited nanomolar antiproliferative activity, thus being essentially equipotent with the natural product. In contrast, the activity of the\n                    <jats:italic>N<\/jats:italic>\n                    \u2010tosyl derivative was significantly reduced.\n                  <\/jats:p>","DOI":"10.1002\/chem.202003996","type":"journal-article","created":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T05:10:08Z","timestamp":1603170608000},"page":"5936-5943","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis of Morpholine\u2010Based Analogues of (\u2212)\u2010Zampanolide and Their Biological Activity"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3810-8407","authenticated-orcid":false,"given":"Christian Paul","family":"Bold","sequence":"first","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences ETH Zurich HCI H405  Vladimir-Prelog-Weg 4 8093 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7844-0861","authenticated-orcid":false,"given":"Melanie","family":"Gut","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences ETH Zurich HCI H405  Vladimir-Prelog-Weg 4 8093 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Sch\u00fcrmann","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences ETH Zurich HCI H405  Vladimir-Prelog-Weg 4 8093 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-8696","authenticated-orcid":false,"given":"Daniel","family":"Lucena\u2010Agell","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u1f79gicas Margarita Salas Consejo Superior de Investigaciones Cient\u00edficas  Ramiro de Maeztu 9 28040 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0978-1555","authenticated-orcid":false,"given":"J\u00fcrg","family":"Gertsch","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Institute of Biochemistry and Molecular Medicine University of Bern  B\u00fchlstrasse 28 3012 Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2743-3319","authenticated-orcid":false,"given":"Jos\u00e9 Fernando","family":"D\u00edaz","sequence":"additional","affiliation":[{"name":"Centro de Investigaciones Biol\u1f79gicas Margarita Salas Consejo Superior de Investigaciones Cient\u00edficas  Ramiro de Maeztu 9 28040 Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0747-9734","authenticated-orcid":false,"given":"Karl\u2010Heinz","family":"Altmann","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Applied Biosciences Institute of Pharmaceutical Sciences ETH Zurich HCI H405  Vladimir-Prelog-Weg 4 8093 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,3]]},"reference":[{"key":"e_1_2_7_1_1","unstructured":"\u00a0"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/minf.202000017"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.2533\/chimia.2007.355"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm801514w"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.9b01285"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2011.12.014"},{"key":"e_1_2_7_7_1","unstructured":"For recent reviews see:"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2019.1604675"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2019.05.003"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.8b00368"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.2533\/chimia.2017.646"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-540-87895-7","volume-title":"Marine Toxins as Research Tools, Vol.\u20051","author":"Fusetani N.","year":"2009"},{"key":"e_1_2_7_13_1","unstructured":"\u00a0"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1614680114"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.11.118"},{"key":"e_1_2_7_16_1","unstructured":"https:\/\/www.midwestern.edu\/departments\/marinepharmacology\/clinical-pipeline.xml. 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