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To provide a basis for structure\u2013activity studies that might eventually lead to improved variants of tiacumicin\u2005B, we have developed an efficient approach to the synthesis of the tiacumicin\u2005B aglycone. The synthesis features a high\u2010yielding intramolecular Suzuki cross\u2010coupling reaction to effect macrocyclic ring closure. Key steps in the synthesis of the macrocyclization precursor were a highly selective, one\u2010pot Corey\u2013Peterson olefination and an ene\u2013diene cross\u2010metathesis reaction. Depending on the reaction conditions, the final deprotection delivered either the fully deprotected tiacumicin\u2005B aglycone or partially protected versions thereof.<\/jats:p>","DOI":"10.1002\/anie.201409510","type":"journal-article","created":{"date-parts":[[2014,12,15]],"date-time":"2014-12-15T16:19:29Z","timestamp":1418660369000},"page":"1937-1940","source":"Crossref","is-referenced-by-count":65,"title":["Total Synthesis of the Tiacumicin\u2005B (Lipiarmycin A3\/Fidaxomicin) Aglycone"],"prefix":"10.1002","volume":"54","author":[{"given":"Florian","family":"Glaus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl\u2010Heinz","family":"Altmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,12,15]]},"reference":[{"key":"e_1_2_2_1_2","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.567"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.40.575"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1039\/C2NP20080E"},{"key":"e_1_2_2_5_2","unstructured":"\u00a0"},{"key":"e_1_2_2_6_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.28.247"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.28.253"},{"key":"e_1_2_2_8_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.28.543"},{"key":"e_1_2_2_9_2","unstructured":"\u00a0"},{"key":"e_1_2_2_10_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.39.1407"},{"key":"e_1_2_2_11_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.39.1413"},{"key":"e_1_2_2_12_2","unstructured":"\u00a0"},{"key":"e_1_2_2_13_2","doi-asserted-by":"publisher","DOI":"10.1039\/p19870001353"},{"key":"e_1_2_2_14_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.36.1312"},{"key":"e_1_2_2_15_2","unstructured":"Y.\u2010K.Shue F. K.Babakhani F. W.Okumu P. S.Sears S. L.Miller\u2010Shangle R. B.Walsh PCT application WO 2005\/112990 A2 2005. See also"},{"key":"e_1_2_2_15_3","unstructured":"PCT application WO 2006\/085838 A1 2006and"},{"key":"e_1_2_2_15_4","unstructured":"US patentapplicationUS 2008\/0269145 A1 2008."},{"key":"e_1_2_2_16_2","first-page":"237","volume":"9","author":"Bedeschi A.","year":"2014","journal-title":"Nat. Prod. Commun."},{"key":"e_1_2_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis358"},{"key":"e_1_2_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis339"},{"key":"e_1_2_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn269"},{"key":"e_1_2_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis337"},{"key":"e_1_2_2_21_2","unstructured":"\u00a0"},{"key":"e_1_2_2_22_2","unstructured":"J. Lucado C. Gould A. 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These data can be obtained free of charge from The Cambridge Crystallographic Data Centre viawww.ccdc.cam.ac.uk\/data_request\/cif."},{"key":"e_1_2_2_37_2","unstructured":"\u00a0"},{"key":"e_1_2_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)71308-6"},{"key":"e_1_2_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)94835-4"},{"key":"e_1_2_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)80374-3"},{"key":"e_1_2_2_41_2","unstructured":"TFA\u2010mediated isomerization of the aldimine mixture derived from8was not investigated as prior experiments with a TBS\u2010protected analogue of8had led to only moderateE\/Zratios of 3:1 to 5:1 for the corresponding enal. 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