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Indeed, the study of 12\u2010membered macrolactones has already led to the discovery of lead drug compounds and new biological targets, which has motivated the development of diverted total synthetic routes to libraries of analogs. This review explores the discovery, biological characterization, and synthesis of several 12\u2010membered macrolactones, exploiting examples that underscore their importance in the drug discovery field. It is our hope that this review will motivate further interest in this class of natural products, a group of molecules that we think merit the classification of \u2018privileged scaffolds\u2019 within the medicinal chemistry community, to further investigate and develop novel compounds with promising bioactivity.<\/jats:p>","DOI":"10.1111\/cbdd.12783","type":"journal-article","created":{"date-parts":[[2016,5,6]],"date-time":"2016-05-06T11:20:05Z","timestamp":1462533605000},"page":"169-191","source":"Crossref","is-referenced-by-count":19,"title":["Twelve\u2010membered macrolactones: privileged scaffolds for the development of new therapeutics"],"prefix":"10.1111","volume":"89","author":[{"given":"Richard S.","family":"Brzozowski","sequence":"first","affiliation":[{"name":"Department of Chemistry Temple University Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"Wuest","sequence":"additional","affiliation":[{"name":"Department of Chemistry Temple University Philadelphia PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,2,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.031"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3NP70090A"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.5b01055"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/np200906s"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/C3NP70058E"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature.2015.18507"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318021111"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5NP00156K"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5NP00127G"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2010.02.018"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00120a002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/9781782622246-00064"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.09.113"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12629"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/sb300092n"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2590"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja909118a"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.10.082"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(03)00020-6"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200503195"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi035501m"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2008.08.003"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja5016052"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(02)00095-9"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/b814603a"},{"key":"e_1_2_11_27_1","first-page":"24","volume":"1","author":"Auerbach T.","year":"2009","journal-title":"Biotechnologia"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01565a073"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja404134f"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/np010146r"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1006\/mben.2000.0167"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00845a037"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1039\/b911200f"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00156a032"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr300129n"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1246\/bcsj.52.1989"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.197805221"},{"key":"e_1_2_11_38_1","first-page":"335","volume":"2","author":"Goyal N.","year":"2010","journal-title":"Synlett"},{"key":"e_1_2_11_39_1","first-page":"286287","volume":"31","author":"Shiina I.","year":"2002","journal-title":"Chem. 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