title: Enantioselective Total Synthesis of Mandelalide A and Isomandelalide A: Discovery of a Cytotoxic Ring-Expanded Isomer.
abstract: The total synthesis of mandelalide A and its ring-expanded macrolide isomer isomandelalide A has been achieved. Unexpected high levels of cytotoxicity were observed with the ring-expanded isomandelalide A with a rank order of potency: mandelalide A > isomandelalide A > mandelalide B. Key aspects of the synthesis include Ag-catalyzed cyclizations (AgCC's) to construct both the THF and THP rings present in the macrocycle, diastereoselective Sharpless dihydroylation of a cis-enyne, and lithium acetylide coupling with a chiral epoxide.
authors.forename: Nagarathanam
authors.initials: N
authors.lastname: Veerasamy
authors.forename: Ankan
authors.initials: A
authors.lastname: Ghosh
authors.forename: Jinming
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Synthetic and Medicinal Chemistry, Tohoku Pharmaceutical University , Sendai 981-8558, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Watanabe
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Serrill
authors.forename: Jane E
authors.initials: JE
authors.lastname: Ishmael
authors.forename: Kerry L
authors.initials: KL
authors.lastname: McPhail
authors.forename: Rich G
authors.initials: RG
authors.lastname: Carter
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003500:Cyclization; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D012834:Silver / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018942:Macrolides; C000611641:isomandelalide A; C000589407:mandelalide A; D012834:Silver