4-亚甲基异恶唑烷-5-酮——一类具有高细胞生长抑制活性的新型α-亚甲基-γ-内酯。
4-Methylideneisoxazolidin-5-ones--a new class of alpha-methylidene-gamma-lactones with high cytostatic activity.
作者信息
Janecki Tomasz, Wasek Tomasz, Rózalski Marek, Krajewska Urszula, Studzian Kazimierz, Janecka Anna
机构信息
Institute of Organic Chemistry, Technical University of Łódź, 90-924 Łódź, Poland.
出版信息
Bioorg Med Chem Lett. 2006 Mar 1;16(5):1430-3. doi: 10.1016/j.bmcl.2005.11.032. Epub 2005 Nov 28.
A novel, general method of synthesis of 4-methylideneisoxazolidin-5-ones 10 is described. The target compounds were synthesized starting from ethyl 2-diethoxyphosphoryl-2-alkenoates 6 or dicyclohexylammonium 4-diethoxyphosphoryl-2-alkenoates 7. Addition of N-methylhydroxylamine hydrochloride to these Michael acceptors, lactonization to 4-diethoxyphosphorylisoxazolidin-5-ones 9, and Horner-Wadsworth-Emmons olefination of formaldehyde using 9 gave the title isoxazolidinones 10. All obtained compounds were tested against L-1210, HL-60, and NALM-6 leukemia cell lines. Several isoxazolidinones 10 were found to be very potent with IC(50)<1 microM. The highest cytostatic activity against HL-60 was observed for 10a and against NALM-6 for 10b with IC(50) values of 0.74 and 0.34 microM, respectively.
描述了一种合成4-亚甲基异恶唑烷-5-酮10的新颖通用方法。目标化合物是从2-二乙氧基磷酰基-2-链烯酸乙酯6或二环己基铵4-二乙氧基磷酰基-2-链烯酸酯7开始合成的。将盐酸N-甲基羟胺添加到这些迈克尔受体中，内酯化生成4-二乙氧基磷酰基异恶唑烷-5-酮9，然后使用9对甲醛进行霍纳-沃兹沃思-埃蒙斯烯烃化反应，得到标题化合物异恶唑烷酮10。所有得到的化合物均针对L-1210、HL-60和NALM-6白血病细胞系进行了测试。发现几种异恶唑烷酮10具有很强的活性，IC(50)<1 microM。观察到10a对HL-60的细胞生长抑制活性最高，10b对NALM-6的细胞生长抑制活性最高，IC(50)值分别为0.74和0.34 microM。
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