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We have designed and synthesized the first examples of 1\u03b1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub> analogs bearing an allenic unit attached to the D ring to restrict the side\u2010chain conformational mobility. The triene system was constructed by a Pd<jats:sup>0<\/jats:sup>\u2010mediated cyclization\/Suzuki\u2010Miyaura cross\u2010coupling process in the presence of an allenic side chain. The allenic moiety was built through an orthoester\u2010Claisen rearrangement of a propargylic alcohol. The biological activity and structure of (22<jats:italic>S<\/jats:italic>)\u20101\u03b1,25\u2010dihydroxy\u201017,20\u2010dien\u201024\u2010homo\u201021\u2010nor\u2010vitamin D<jats:sub>3<\/jats:sub> bound to binding domain of the vitamin D receptor, provide information concerning side\u2010chain conformational requirements for biological activity.<\/jats:p>","DOI":"10.1002\/chem.202101578","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T08:40:33Z","timestamp":1625474433000},"page":"13384-13389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Design, Synthesis, Evaluation and Structure of Allenic 1\u03b1,25\u2010Dihydroxyvitamin D<sub>3<\/sub> Analogs with Locked Mobility at C\u201017"],"prefix":"10.1002","volume":"27","author":[{"given":"Ram\u00f3n","family":"Fraga","sequence":"first","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Laboratorio de Investigaci\u00f3n Ignacio Ribas Universidad de Santiago  Avda Ciencias s\/n 15782 Santiago de Compostela Spain"}]},{"given":"Kateryna","family":"Len","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC)  67400 Illkirch France"},{"name":"Institut National de La Sant\u00e9 et de La Recherche M\u00e9dicale (INSERM), U1258  67400 Illkirch France"},{"name":"Centre National de Recherche Scientifique (CNRS), UMR7104  67400 Illkirch France"},{"name":"Universit\u00e9 de Strasbourg  67400 Illkirch France"}]},{"given":"Regis","family":"Lutzing","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC)  67400 Illkirch France"},{"name":"Institut National de La Sant\u00e9 et de La Recherche M\u00e9dicale (INSERM), U1258  67400 Illkirch France"},{"name":"Centre National de Recherche Scientifique (CNRS), UMR7104  67400 Illkirch France"},{"name":"Universit\u00e9 de Strasbourg  67400 Illkirch France"}]},{"given":"Gilles","family":"Laverny","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC)  67400 Illkirch France"},{"name":"Institut National de La Sant\u00e9 et de La Recherche M\u00e9dicale (INSERM), U1258  67400 Illkirch France"},{"name":"Centre National de Recherche Scientifique (CNRS), UMR7104  67400 Illkirch France"},{"name":"Universit\u00e9 de Strasbourg  67400 Illkirch France"}]},{"given":"Julian","family":"Loureiro","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias da Universidade do Porto  Portugal"}]},{"given":"Miguel A.","family":"Maestro","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Laboratorio de Investigaci\u00f3n Ignacio Ribas Universidad de Santiago  Avda Ciencias s\/n 15782 Santiago de Compostela Spain"},{"name":"Departamento de Qu\u00edmica-CICA Facultad de Ciencias Universidad de A Coru\u00f1a  Campus da Zapateira s\/n 15071 A Coru\u00f1a Spain"}]},{"given":"Natacha","family":"Rochel","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique et de Biologie Mol\u00e9culaire et Cellulaire (IGBMC)  67400 Illkirch France"},{"name":"Institut National de La Sant\u00e9 et de La Recherche M\u00e9dicale (INSERM), U1258  67400 Illkirch France"},{"name":"Centre National de Recherche Scientifique (CNRS), UMR7104  67400 Illkirch France"},{"name":"Universit\u00e9 de Strasbourg  67400 Illkirch France"}]},{"given":"Enrique","family":"Rodriguez\u2010Borges","sequence":"additional","affiliation":[{"name":"LAQV\/REQUIMTE Departamento de Qu\u00edmica e Bioqu\u00edmica Faculdade de Ci\u00eancias da Universidade do Porto  Portugal"}]},{"given":"Antonio","family":"Mouri\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica Org\u00e1nica Laboratorio de Investigaci\u00f3n Ignacio Ribas Universidad de Santiago  Avda Ciencias s\/n 15782 Santiago de Compostela Spain"}]}],"member":"311","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3283939"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-012-9619-0"},{"key":"e_1_2_7_3_1","unstructured":"\u00a0"},{"key":"e_1_2_7_4_2","first-page":"200","volume":"16","author":"Bouillon R.","year":"1995","journal-title":"Endocr. 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