title: On the total synthesis and preliminary biological evaluations of 15(R) and 15(S) aza-dEpoB: a Mitsunobu inversion at C15 in pre-epothilone fragments.
abstract: [reaction-see text] The syntheses of two epothilone analogues, 15(S)-aza-12,13-desoxyepothilone B and the epimeric 15(R)-aza-12,13-desoxyepothilone B, are described. A Mitsunobu inversion was utilized for elaboration of pre-epothilone fragments to the corresponding macrolactam. Tubulin binding and cytotoxicity profiles of these analogues are presented.
authors.affiliation: Laboratories for Bioorganic Chemistryand Biochemical Pharmacology, Sloan-Kettering Institute for Cancer Research, New York, NY 10021, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Stachel
authors.forename: M D
authors.initials: MD
authors.lastname: Chappell
authors.forename: C B
authors.initials: CB
authors.lastname: Lee
authors.forename: S J
authors.initials: SJ
authors.lastname: Danishefsky
authors.forename: T C
authors.initials: TC
authors.lastname: Chou
authors.forename: L
authors.initials: L
authors.lastname: He
authors.forename: S B
authors.initials: SB
authors.lastname: Horwitz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C410207:15-aza-12,13-desoxyepothilone B; D000970:Antineoplastic Agents; D001372:Aza Compounds; D034261:Epothilones; D004852:Epoxy Compounds; D007783:Lactones; D013844:Thiazoles; D014404:Tubulin; C114026:desoxyepothilone B; C093788:epothilone B