title: Synthesis of (±)-actinophyllic acid and analogs: applications of cascade reactions and diverted total synthesis.
abstract: Actinophyllic acid is a biologically active indole alkaloid with a unique structural framework that incorporates five contiguous stereocenters. A total synthesis of (±)-actinophyllic acid has been completed that proceeds in only 10 steps from readily available, known compounds and with the isolation of nine intermediates. The synthesis features a novel cascade of reactions of N-stabilized carbocations with π-nucleophiles to create the tetracyclic core of actinophyllic acid in a single chemical operation. This pivotal cascade sequence generates substructures of the actinophyllic acid core that are not otherwise accessible, and one key intermediate was modified to furnish several novel compounds having potentially promising anticancer activity, one of which induces cell death in a wide range of cancer cell lines.
authors: Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
authors: Brett A
authors: BA
authors: Granger
authors: Ivan T
authors: IT
authors: Jewett
authors: Jeffrey D
authors: JD
authors: Butler
authors: Bruce
authors: B
authors: Hua
authors: Claire E
authors: CE
authors: Knezevic
authors: Elizabeth I
authors: EI
authors: Parkinson
authors: Paul J
authors: PJ
authors: Hergenrother
authors: Stephen F
authors: SF
authors: Martin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D026121:Indole Alkaloids; C500686:actinophyllic acid