title: Amphidinolide B: total synthesis, structural investigation, and biological evaluation.
abstract: The total syntheses of amphidinolide B1 and the proposed structure of amphidinolide B2 have been accomplished. Key aspects of this work include the development of a practical, non-transition-metal-mediated method for the construction of the C13-C15 diene, the identification of α-chelation and dipole minimization models for diastereoselective methyl ketone aldol reactions, the discovery of a spontaneous Horner-Wadsworth-Emmons macrocyclization strategy, and the development of a novel late stage method for construction of an allylic epoxide moiety. The originally proposed structure for amphidinolide B2 and diastereomers thereof display potent antitumor activities with IC50 values ranging from 3.3 to 94.5 nM against human solid and blood tumor cells. Of the different stereoisomers, the proposed structure of amphidinolide B2 is over 12-fold more potent than the C8,9-epimer and C18-epimer in human DU145 prostate cancer cells. These data suggest that the epoxide stereochemistry is a significant factor for anticancer activity.
authors: Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, United States.
authors: Liang
authors: L
authors: Lu
authors: Wei
authors: W
authors: Zhang
authors: Sangkil
authors: S
authors: Nam
authors: David A
authors: DA
authors: Horne
authors: Richard
authors: R
authors: Jove
authors: Rich G
authors: RG
authors: Carter
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004852:Epoxy Compounds / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism; D000097442:Amphidinolides
chemical_list: D000970:Antineoplastic Agents; D004852:Epoxy Compounds; D018942:Macrolides; C511225:amphidinolide B1; D000097442:Amphidinolides; C584032:amphidinolide B2