title: Antitumor agents. 11. Synthesis and cytotoxic activity of epoxides of helenalin related derivatives.
abstract: Several epoxides of helenalin related derivatives have been synthesized in an effort to evaluate the potential significance of the epoxycyclopentanone moiety for cytotoxic activity against the growth of tissue culture cells originating from human epidermoid carcinoma of larynx (H.Ep-2). Helenalin (1) was converted to the monoepoxy derivative 2 and the diepoxy derivative 3 by alkaline hydrogen peroxide at different temperatures. Alternative synthesis of 2 was achieved by a convenient method of protecting the alpha-methylene grouping of the gamma-lactone, i.e., epoxidation of helenalin dimethylamine adduct 4, followed by treatment of the reaction product 5 with m-chloroperbenzoic acid. 2,3-Epoxy-11,13-dihydrohelenalin (8) was prepared by direct epoxidation of 11,13-dihydrohelenalin (7). Treatment of mexicanin A (9) with m-chloroperbenzoic acid gave, in addition to the 1,2-epoxy derivative 10, 1-alpha-hydroxyhelenalin (11) which furnished an acetate (12) upon acetylation. Catalytic hydrogenation of 10 yielded the dihydroepoxide 13. Treatment of 1 or acetylhelenalin (15) with Ac2O-p-TsOH gave the same acetyl dienol acetate (14). Epoxidation of 14 with m-chloroperbenzoic acid gave 1,beta hydroxyhelenalin (19) and a mixture of monoepoxides (17 and 18) which yielded 19 and 11 upon silica gel chromatography. The results of the cytotoxicity test of the compounds studied indicate that either an alpha- or a beta-epoxycyclopentanone moiety in helenalin related derivatives contributes significantly to the cytotoxicity. Furthermore, this cytotoxicity appears to be independent of the presence or absence of an alpha-epoxy-gamma-lactonic moiety.
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D002478:Cells, Cultured / Q000187:drug effects; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007822:Laryngeal Neoplasms; D009682:Magnetic Resonance Spectroscopy; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004852:Epoxy Compounds; D012717:Sesquiterpenes