Institute of Organic Chemistry, Technical University of Lodz, Zeromskiego 116, 90-924 Łódź, Poland.
Eur J Med Chem. 2010 Feb;45(2):710-8. doi: 10.1016/j.ejmech.2009.11.018. Epub 2009 Nov 14.
We present a simple and general strategy for the synthesis of beta,delta-disubstituted-alpha-methylene-delta-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 alpha-methylene-delta-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 alpha-methylene-gamma-lactones is also discussed.
我们提出了一种简单而通用的策略，从易得的叔丁基 2-（二乙氧基膦酰基）-2-烯酸酯出发，合成β，δ-二取代-α-亚甲基-δ-内酯。详细的合成方案包括吡咯烷催化的丙酮迈克尔加成、羰基的立体选择性还原、内酯化，最后是与甲醛的 Horner-Wadsworth-Emmons 反应。所有的α-亚甲基-δ-内酯均在体外对小鼠白血病细胞系 L-1210 以及两种人白血病细胞系 HL-60 和 NALM-6 进行了评估。还讨论了与相应的α-亚甲基-γ-内酯的细胞毒性活性比较。
