title: Total synthesis of tubulysin U and its C-4 epimer.
abstract: The Tup fragments of tubulysins were synthesized with a tandem reaction as the key step, and unexpected diastereoselectivity was observed in the first Grignard addition stage. The coupling of the enolate of a thiazolyl ketone with chiral sulfinimines furnished the backbone of the Tuv fragment with over 100:1 d.r. and high yield. Thus, tubulysin U and C-4 epi-tubulysin U were prepared in a highly selective and efficient manner. The results of the MTT assay furthermore indicated that C-4 epi-tubulysin U maintained significant growth inhibition activities against several cancer cell lines.
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, 300071, Tianjin, PR China.
authors.forename: Xiu-dong
authors.initials: XD
authors.lastname: Yang
authors.forename: Chang-ming
authors.initials: CM
authors.lastname: Dong
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Ya-hui
authors.initials: YH
authors.lastname: Ding
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Ma
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D006801:Humans; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010875:Pipecolic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D010875:Pipecolic Acids; C516471:tubulysin U