{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:14:30Z","timestamp":1769148870397,"version":"3.49.0"},"reference-count":100,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2020,10,2]],"date-time":"2020-10-02T00:00:00Z","timestamp":1601596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["200021_126511"],"award-info":[{"award-number":["200021_126511"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["200020_143269"],"award-info":[{"award-number":["200020_143269"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Efforts are described towards the total synthesis of the bacterial macrolide rhizoxin F, which is a potent tubulin assembly and cancer cell growth inhibitor. A significant amount of work was expanded on the construction of the rhizoxin core macrocycle by ring-closing olefin metathesis (RCM) between C(9) and C(10), either directly or by using relay substrates, but in no case was ring-closure achieved. Macrocycle formation was possible by ring-closing alkyne metathesis (RCAM) at the C(9)\/C(10) site. The requisite diyne was obtained from advanced intermediates that had been prepared as part of the synthesis of the RCM substrates. While the direct conversion of the triple bond formed in the ring-closing step into the C(9)-C(10) E double bond of the rhizoxin macrocycle proved to be elusive, the corresponding Z isomer was accessible with high selectivity by reductive decomplexation of the biscobalt hexacarbonyl complex of the triple bond with ethylpiperidinium hypophosphite. Radical-induced double bond isomerization, full elaboration of the C(15) side chain, and directed epoxidation of the C(11)-C(12) double bond completed the total synthesis of rhizoxin F.<\/jats:p>","DOI":"10.3390\/molecules25194527","type":"journal-article","created":{"date-parts":[[2020,10,3]],"date-time":"2020-10-03T07:22:16Z","timestamp":1601709736000},"page":"4527","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Ring-Closing Metathesis Approaches towards the Total Synthesis of Rhizoxins"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4273-2942","authenticated-orcid":false,"given":"Marc","family":"Liniger","sequence":"first","affiliation":[{"name":"ETH Z\u00fcrich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, 8093 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian M.","family":"Neuhaus","sequence":"additional","affiliation":[{"name":"ETH Z\u00fcrich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, 8093 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0747-9734","authenticated-orcid":false,"given":"Karl-Heinz","family":"Altmann","sequence":"additional","affiliation":[{"name":"ETH Z\u00fcrich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, 8093 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.7164\/antibiotics.37.354","article-title":"Studies on macrocyclic lactone antibiotics. vii. structure of a phytotoxin \"Rhizoxin\" produced by Rhizopus Chinensis","volume":"37","author":"Iwasaki","year":"1984","journal-title":"J. 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