title: Total Synthesis and in Vitro Anti-Tumor-Promoting Activities of Racemic Acetophenone Monomers from Acronychia trifoliolata.
abstract: Six acetophenone derivatives, acronyculatins I (1), J (2), K (3), L (4), N (5), and O (6), were recently isolated from Acronychia trifoliolata, and the structure of the known acronyculatin B (7) was revised. Because of the limited quantities of isolated products as well as their structure similarity, racemic acronyculatins I-L, N, O, and B (1-7) were synthesized to confirm their structures and to obtain sufficient material for biological evaluation. Trihydroxyacetophenone was converted to the target compounds by various sequences of hydroxy group protection, allylation or prenylation, and epoxidation followed by cyclization. C-Prenylations were carried out by direct addition of a prenyl group or through 1,3- or 3,3-sigmatropic rearrangement. The synthesized racemic compounds were evaluated in an anti-tumor-promoting assay using the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate in Raji cells. All tested compounds significantly inhibited EBV-EA activation. Especially, racemic acronyculatin I (1) displayed the most potent inhibitory effects, with an IC50value of 7.3 μM.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morita
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Saito
authors.forename: Katsunori
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University , Kyoto 606-8502, Japan.
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: International Health & Welfare University Hospital , Nasushiobara, Tochigi 329-2763, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Ichiishi
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-7568, United States.|Chinese Medicine Research and Development Center, China Medical University and Hospital , 2 Yuh-Der Road, Taichung, 40447, Taiwan.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599-7568, United States.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakagawa-Goto
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000956:Antigens, Viral / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology; D004854:Herpesvirus 4, Human / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms; D027821:Rutaceae / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D000956:Antigens, Viral; D002273:Carcinogens; C033305:Epstein-Barr virus early antigen; D013755:Tetradecanoylphorbol Acetate