Synthesis and cytotoxic evaluation of β-alkyl or β-aryl-δ-methyl-α-methylene-δ-lactones. Comparison with the corresponding γ-lactones
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- 作者：Ł ; ukasz Albrecht ; Jakub Wojciechowski ; Anna Albrecht ; Wojciech M. Wolf ; Anna Janecka ; Kazimierz Studzian ; Urszula Krajewska ; Marek Ró ; ż ; alski ; Tomasz Janecki ; Henryk Krawczyk
- 关键词：α ; -Methylene-γ ; -lactones ; α ; -Methylene-δ ; -lactones ; Horner– ; Wadsworth– ; Emmons reaction ; Diastereoselective synthesis ; Cytotoxic activity
- 刊名：European Journal of Medicinal Chemistry
- 出版年：2010
- 出版时间：February 2010
- 年：2010
- 卷：45
- 期：2
- 页码：710-718
- 全文大小：512 K
文摘
We present a simple and general strategy for the synthesis of β,δ-disubstituted-α-methylene-δ-lactones starting from easily available tert-butyl 2-(diethoxyphosphoryl)alk-2-enoates. The elaborated synthetic protocol includes pyrrolidine-catalyzed Michael addition of acetone, diastereoselective reduction of the carbonyl group, lactonization and finally the Horner–Wadsworth–Emmons reaction with formaldehyde. All α-methylene-δ-lactones were evaluated in vitro against mouse leukemia cell line L-1210 and two human leukemia cell lines HL-60 and NALM-6. Comparison of cytotoxic activity with corresponding α-methylene-γ-lactones is also discussed.