title: Design and synthesis of 2-phenyl-1,4-dioxa-spiro[4.5]deca-6,9-dien-8-ones as potential anticancer agents starting from cytotoxic spiromamakone A.
abstract: The spirocycle is a key structure found in many bioactive compounds. From the cytotoxic and spirocyclic natural product, spiromamakone A (1) and its analogues, a more synthetically accessible spiroacetal template 4 was designed based on structural similarity analysis. A total of 50 compounds were rapidly synthesized in only one or two synthetic steps from the starting compound, and their cytotoxicity was evaluated. As a result, (±)-(2R*,5R*)-2-(4-iodophenyl)-7-chloro-1,4-dioxa-spiro[4.5]deca-6,9-dien-8-one (7d-II) was discovered and found to be fifteen-fold more cytotoxic than 1. The easily accessible spiroacetal 7d-II appeared to act in a manner similar to the highly oxidized natural product, spiromamakone A (1).
authors.affiliation: Department of Applied Chemistry, Tokyo Institute of Technology, 2-12-1, Ookayama, Meguro-ku, Tokyo 152-8552, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Fuse
authors.forename: Kennichi
authors.initials: K
authors.lastname: Inaba
authors.forename: Motoki
authors.initials: M
authors.lastname: Takagi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tanaka
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Hirokawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Johmoto
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Uekusa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shin-Ya
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Doi
mesh_terms: D000080:Acetals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D008968:Molecular Conformation; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000080:Acetals; D000970:Antineoplastic Agents; D009281:Naphthalenes; D013141:Spiro Compounds; C517106:spiro-mamakone A
keywords: Anticancer agent; IXNMJGORXMJZOQ-KGLIPLIRSA-N; Spiroacetal; Spirocycle; Spiromamakone A; Spiropreussione B