title: Probing the SAR of dEpoB via chemical synthesis: a total synthesis evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B.
abstract: A practical total synthesis of 26-(1,3-dioxolanyl)-12,13-desoxyepothilone B (26-dioxolanyl dEpoB) was accomplished in a highly convergent manner. A novel sequence was developed to produce the vinyl iodide segment 17 in high enantiomeric excess, which was used in a key B-alkyl Suzuki merger. Subsequently, a Yamaguchi macrocyclization formed the core lactone, while a selective oxidation and a late stage Noyori acetalization incorporated the dioxolane functionality. Sufficient amounts of synthetic 26-dioxolane dEpoB were produced using this sequence for an in vivo analysis in mice containing xenograft CCRF-CEM tumors.
authors.affiliation: Laboratories for Bioorganic Chemistry and Laboratories for Preclinical Pharmacology, The Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Chappell
authors.forename: Christina R
authors.initials: CR
authors.lastname: Harris
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kuduk
authors.forename: Aaron
authors.initials: A
authors.lastname: Balog
authors.forename: Zhicai
authors.initials: Z
authors.lastname: Wu
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Chul Bom
authors.initials: CB
authors.lastname: Lee
authors.forename: Shawn J
authors.initials: SJ
authors.lastname: Stachel
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Danishefsky
authors.forename: Ting-Chao
authors.initials: TC
authors.lastname: Chou
authors.forename: Yongbiao
authors.initials: Y
authors.lastname: Guan
mesh_terms: D000818:Animals; D018450:Disease Progression; D034261:Epothilones / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D004852:Epoxy Compounds / Q000737:chemistry; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D034261:Epothilones; D004852:Epoxy Compounds; C114026:desoxyepothilone B