Lee K H, Kim S H, Furukawa H, Piantadosi C
J Med Chem. 1975 Jan;18(1):59-63. doi: 10.1021/jm00235a013.
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.
为了评估环氧环戊酮部分对源自人喉表皮样癌（H.Ep - 2）的组织培养细胞生长的细胞毒性活性的潜在重要性，已合成了几种海伦内酯相关衍生物的环氧化物。在不同温度下，用碱性过氧化氢将海伦内酯（1）转化为单环氧化衍生物2和二环氧化衍生物3。通过一种保护γ-内酯的α-亚甲基基团的简便方法实现了2的另一种合成，即海伦内酯二甲胺加合物4的环氧化，然后用间氯过苯甲酸处理反应产物5。通过11,13 - 二氢海伦内酯（7）的直接环氧化制备了2,3 - 环氧 - 11,13 - 二氢海伦内酯（8）。用间氯过苯甲酸处理墨西哥宁A（9），除了得到1,2 - 环氧衍生物10外，还得到1 - α - 羟基海伦内酯（11），其乙酰化后得到乙酸酯（12）。10的催化氢化得到二氢环氧化物13。用Ac2O - 对甲苯磺酸处理1或乙酰海伦内酯（15）得到相同的乙酰二烯醇乙酸酯（14）。用间氯过苯甲酸对14进行环氧化得到1,β - 羟基海伦内酯（19）和单环氧化物混合物（17和18），它们在硅胶柱色谱上得到19和11。所研究化合物的细胞毒性测试结果表明，海伦内酯相关衍生物中的α - 或β - 环氧环戊酮部分对细胞毒性有显著贡献。此外，这种细胞毒性似乎与α - 环氧 - γ - 内酯部分的存在与否无关。
