{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:52:02Z","timestamp":1790031122216,"version":"4.0.1"},"reference-count":68,"publisher":"Wiley","issue":"38","license":[{"start":{"date-parts":[[2010,8,23]],"date-time":"2010-08-23T00:00:00Z","timestamp":1282521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2010,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The total syntheses of tetrapeptides tubulysins\u2005D (<jats:bold>1\u2009b<\/jats:bold>), U (<jats:bold>1\u2009c<\/jats:bold>), and V (<jats:bold>1\u2009d<\/jats:bold>), which are potent tubulin polymerization inhibitors, are described. The synthesis of Tuv (<jats:bold>2<\/jats:bold>), an unusual amino acid constituent of tubulysins, includes an 1,3\u2010dipolar cycloaddition reaction of chiral nitrone <jats:sc>D<\/jats:sc>\u2010<jats:bold>6<\/jats:bold> derived from <jats:sc>D<\/jats:sc>\u2010gulose with <jats:italic>N<\/jats:italic>\u2010acryloyl camphor sultam (\u2212)\u2010<jats:bold>9<\/jats:bold> employing the double asymmetric induction, whereas the synthesis of Tup (<jats:bold>20<\/jats:bold>), another unusual amino acid, involves a stereoselective Evans aldol reaction of (<jats:italic>Z<\/jats:italic>)\u2010boron enolate generated from (<jats:italic>S<\/jats:italic>)\u20104\u2010isopropyl\u20103\u2010propionyl\u20102\u2010oxazolidinone with <jats:italic>N<\/jats:italic>\u2010protected phenylalaninal and a subsequent Barton deoxygenation protocol. We accomplished the total syntheses of tubulysins\u2005U (<jats:bold>1\u2009c<\/jats:bold>) and V (<jats:bold>1\u2009d<\/jats:bold>) by using these methodologies, in which the isoxazolidine ring was used as the effective protective group for \u03b3\u2010amido alcohol functionality. Furthermore, to understand the structure\u2010activity relationship of tubulysins, we synthesized tubulysin\u2005D (<jats:bold>1\u2009b<\/jats:bold>) and cyclo\u2010tubulysin\u2005D (<jats:bold>1\u2009e<\/jats:bold>) from <jats:bold>2<\/jats:bold>\u2010Me and <jats:bold>20<\/jats:bold>, and <jats:italic>ent<\/jats:italic>\u2010tubulysin\u2005D (<jats:italic>ent<\/jats:italic>\u2010<jats:bold>1\u2009d<\/jats:bold>) from <jats:italic>ent<\/jats:italic>\u2010<jats:bold>2<\/jats:bold>\u2010Me and <jats:italic>ent<\/jats:italic>\u2010<jats:bold>20<\/jats:bold>, respectively. The preliminary results regarding their biological activities are also reported.<\/jats:p>","DOI":"10.1002\/chem.201000963","type":"journal-article","created":{"date-parts":[[2010,8,28]],"date-time":"2010-08-28T23:32:26Z","timestamp":1283038346000},"page":"11678-11688","source":"Crossref","is-referenced-by-count":64,"title":["Total Syntheses of Tubulysins"],"prefix":"10.1002","volume":"16","author":[{"given":"Taku","family":"Shibue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Hirai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwao","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyoshi","family":"Morita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyuma","family":"Masu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Azumaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Tamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,8,23]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.53.879"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200460147"},{"key":"e_1_2_6_2_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200460147"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1351\/pac200375020167"},{"key":"e_1_2_6_4_2","unstructured":"\u00a0"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-005-1542-0"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200601259"},{"key":"e_1_2_6_6_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200601259"},{"key":"e_1_2_6_6_4","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200790053"},{"key":"e_1_2_6_6_5","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200790053"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200500421"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051735"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja067177z"},{"key":"e_1_2_6_10_2","unstructured":"For the synthesis of tubulysins\u2005U and V see:"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200604557"},{"key":"e_1_2_6_11_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200604557"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm8013579"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol902320w"},{"key":"e_1_2_6_14_2","unstructured":"For the synthesis of tubulysin analogues see:"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol070415q"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1747-0285.2007.00541.x"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200701057"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm701321p"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.03.046"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.07.041"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo800384x"},{"key":"e_1_2_6_22_2","unstructured":"For studies on the synthesis of tubuvaline and tubuphenylalanine see:"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol048986v"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol048252i"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200500043"},{"key":"e_1_2_6_26_2","first-page":"1341","author":"Shankar P. 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