title: Total syntheses of parthenolide and its analogues with macrocyclic stereocontrol.
abstract: The first total synthesis of parthenolide (1) is described. The key feature of this synthesis is the formation of a 10-membered carbocylic ring by a macrocyclic stereocontrolled Barbier reaction, followed by a photoinduced Z/E isomerization. The biological evaluation of a small library of parthenolide analogues (19, 33, and 34) disclosed a preliminary structure-activity relationship (SAR). The results revealed that the C1, C10 double bond configuration of parthenolide has little or no effect on the activity, and the C6 and C7 configurations of the lactone ring have a moderate impact on the activities against some cancer cell lines.
authors.affiliation: The State Key Laboratory of Medicinal Chemical Biology, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Pharmacy, and Tianjin Key Laboratory of Molecular Drug Research, Nankai University , Tianjin 300071, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Long
authors.forename: Shan-Feng
authors.initials: SF
authors.lastname: Zhang
authors.forename: Pan-Pan
authors.initials: PP
authors.lastname: Wang
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Zhong-Jin
authors.initials: ZJ
authors.lastname: Yang
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects; D009369:Neoplasms; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D012717:Sesquiterpenes; C002669:parthenolide