title: Synthesis of 7beta-sulfur analogues of paclitaxel utilizing a novel epimerization of the 7alpha-thiol group.
abstract: Paclitaxel analogues with a sulfur group at the 7beta position were required for SAR studies. Attempts to generate these compounds by displacing a 7alpha leaving group with sulfur nucleophiles were unsuccessful. Instead, these compounds were successfully prepared from a 7beta-thiol intermediate that was obtained by a base-catalyzed epimerization of the 7alpha-thiol derivative. The epimerization presumably proceeds through a thioaldehyde intermediate and exhibits the opposite stereochemical preference of its oxygen counterpart.
authors.affiliation: Bristol Myers-Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, Connecticut 06492, USA. harold.mastalerz@bms.com
authors.forename: H
authors.initials: H
authors.lastname: Mastalerz
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: J
authors.initials: J
authors.lastname: Kadow
authors.forename: C
authors.initials: C
authors.lastname: Fairchild
authors.forename: B
authors.initials: B
authors.lastname: Long
authors.forename: D M
authors.initials: DM
authors.lastname: Vyas
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013438:Sulfhydryl Compounds; D017239:Paclitaxel