Higuchi Yohsuke, Shimoma Fumito, Ando Masayoshi
Graduate School of Science and Technology, and Department of Chemistry and Chemical Engineering, Faculty of Engineering, Niigata University, 2-8050 Ikarashi, Niigata 950-2181, Japan.
J Nat Prod. 2003 Jun;66(6):810-7. doi: 10.1021/np020586y.
A reliable method was developed for the synthesis of cis-fused alpha-methylene gamma-lactones via alpha-methyl gamma-lactones. Bromination of alpha-methyl gamma-lactones with LDA/CBr(4) or TMSOTf/PTAB and successive dehydrobromination with DBU or TBAF of the resulting alpha-bromo-alpha-methyl gamma-lactones gave the desired alpha-methylene gamma-lactones in high yield. This method was successfully applied to the synthesis of biologically active compounds. alpha-Methylene gamma-lactone derivatives 1c, 2c, 4c, and 17 showed cell growth inhibitory activity to P388 lymphocytic leukemia. They also showed significant activities to crop diseases. Thus, alpha-methylene gamma-lactone 1c showed preventive activity in controlling scab of apple caused by Venturia inaequalis. alpha-Methylene gamma-lactones 2c, 4c, 17, and 18 also showed significant preventive activities in controlling damping off of cucumber caused by Pythium aphanidermatum.
通过α-甲基γ-内酯开发了一种可靠的方法来合成顺式稠合的α-亚甲基γ-内酯。用LDA/CBr(4)或TMSOTf/PTAB对α-甲基γ-内酯进行溴化反应，并对所得的α-溴-α-甲基γ-内酯用DBU或TBAF进行连续的脱溴化氢反应，以高产率得到所需的α-亚甲基γ-内酯。该方法成功应用于生物活性化合物的合成。α-亚甲基γ-内酯衍生物1c、2c、4c和17对P388淋巴细胞白血病显示出细胞生长抑制活性。它们对作物病害也表现出显著活性。因此，α-亚甲基γ-内酯1c在防治由苹果黑星菌引起的苹果黑星病方面显示出预防活性。α-亚甲基γ-内酯2c、4c、17和18在防治由瓜果腐霉引起的黄瓜猝倒病方面也显示出显著的预防活性。
