title: Epothilone D and its 9-Methyl analogues: combinatorial syntheses, conformation, and biological activities.
abstract: Epothilone D (Epo D) and its 9-Methyl conformational analogues were synthesized through a highly efficient combinatorial approach. The fragment E was synthesized in 11 total steps with 6 longest linear steps, and each aldehyde B was prepared via a 3-step sequence. Starting from the common precursor E and a suitable aldehydes B, each target molecule were obtained in only 4 steps. The 9-(S)-epo D and 9-(R)-epo D demonstrated significant difference in inhibition activities against cancer cell lines and in conformational analysis.
authors.affiliation: State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin 300071, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Sang
authors.forename: Peng
authors.initials: P
authors.lastname: Feng
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Yahui
authors.initials: Y
authors.lastname: Ding
authors.forename: Xiyan
authors.initials: X
authors.lastname: Duan
authors.forename: Jiadai
authors.initials: J
authors.lastname: Zhai
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Ma
authors.forename: Bin
authors.initials: B
authors.lastname: Zhang
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Lin
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D034261:Epothilones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008954:Models, Biological; D015394:Molecular Structure
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C114026:desoxyepothilone B
keywords: Analogues; Bioactivity; Epothilone; Structure activity relationship; Total synthesis