title: A novel D-ring modified taxoid: synthesis and biological evaluation of a γ-lactone analogue of docetaxel.
abstract: The synthesis of a novel D-ring modified docetaxel analogue, in which the oxetane ring is replaced with a γ-lactone, was achieved from 10-deacetylbaccatin III. The key steps of the synthesis include the direct acetylation of the secondary hydroxyl group at C-5 and D-ring opening and intramolecular aldol reaction to form the γ-lactone. In MTT assays, this analogue proved to have equipotent cytotoxicity relative to paclitaxel towards HCT8, HePG2 and BGC23 cancer cell lines, and be more potent than paclitaxel against A549 and A375. It represents the first example of D-ring modified taxoids with significant cytotoxicity.
authors.affiliation: Department of Chemistry of Medicinal Natural Products, Sichuan University, No. 17, Duan 3, Renmin Nan Road, Chengdu 610041, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Zhan-Kun
authors.initials: ZK
authors.lastname: Yang
authors.forename: Qiao-Hong
authors.initials: QH
authors.lastname: Chen
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Chen
authors.forename: Feng-Peng
authors.initials: FP
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007783:Lactones / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D043823:Taxoids; D000077143:Docetaxel