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The first stage of the two\u2010step synthesis of coumestrol involved a modified aerobic oxidative cross\u2010coupling between ethyl 2\u2010(2,4\u2010dimethoxybenzoyl)acetate and 3\u2010methoxyphenol, with FeCl<jats:sub>3<\/jats:sub> (10\u2005mol\u2009%) as the catalyst. The benzofuran coupling product was then subjected to sequential deprotection and lactonization steps, affording the natural product in 59\u2009% overall yield. Based on this new methodology other coumestrol analogues were prepared, and their effects on the proliferation of the estrogen receptor (ER)\u2010dependent MCF\u20107 and of the ER\u2010independent MDA\u2010MB\u2010231 breast cancer cells were tested. As a result, new types of estrogen receptor ligands having an acetamide group instead of the 9\u2010hydroxyl group of coumestrol were discovered. Both 9\u2010acetamido\u2010coumestrol and 8\u2010acetamidocoumestrol were found more active than the natural product against estrogen\u2010dependent MCF\u20107 breast cancer cells, with IC<jats:sub>50<\/jats:sub> values of 30 and 9\u2005n<jats:sc>M<\/jats:sc>, respectively.<\/jats:p>","DOI":"10.1002\/chem.201300389","type":"journal-article","created":{"date-parts":[[2013,8,15]],"date-time":"2013-08-15T02:05:43Z","timestamp":1376532343000},"page":"13575-13583","source":"Crossref","is-referenced-by-count":65,"title":["Aerobic Iron\u2010Based Cross\u2010Dehydrogenative Coupling Enables Efficient Diversity\u2010Oriented Synthesis of Coumestrol\u2010Based Selective Estrogen Receptor Modulators"],"prefix":"10.1002","volume":"19","author":[{"given":"Umesh A.","family":"Kshirsagar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regev","family":"Parnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagit","family":"Goldshtein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rivka","family":"Ofir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raz","family":"Zarivach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron","family":"Pappo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,8,14]]},"reference":[{"key":"e_1_2_6_1_2","unstructured":"\u00a0"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr100280d"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr100379j"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr100198w"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar800164n"},{"key":"e_1_2_6_6_2","unstructured":"\u00a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol202749x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2010.10.041"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol9002509"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200900341"},{"key":"e_1_2_6_10_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200900341"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1039\/b911031c"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo902093p"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200801367"},{"key":"e_1_2_6_13_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200801367"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200802215"},{"key":"e_1_2_6_14_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200802215"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.200700686"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200503255"},{"key":"e_1_2_6_16_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200503255"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601687103"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja050058j"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0460763"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0516054"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja105442m"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/460197a"},{"key":"e_1_2_6_23_2","unstructured":"\u00a0"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja809405c"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja804159y"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200704830"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05569"},{"key":"e_1_2_6_28_2","doi-asserted-by":"crossref","unstructured":"P.\u2005S. 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