Synthesis and cytotoxic activity of γ-aryl substituted α-alkylidene-γ-lactones and α-alkylidene-γ-lactams

被引：62

作者：

Albrecht, Anna ^{[1
]}

Koszuk, Jacek F. ^{[1
]}

Modranka, Jakub ^{[1
]}

Rozalski, Marek ^{[2
]}

Krajewska, Urszula ^{[2
]}

Janecka, Anna ^{[3
]}

Studzian, Kazimierz ^{[3
]}

Janecki, Tomasz ^{[1
]}

机构：

[1] Tech Univ Lodz, Inst Organ Chem, PL-90924 Lodz, Poland

[2] Med Univ Lodz, Fac Pharm, Dept Pharmaceut Biochem, PL-90151 Lodz, Poland

[3] Med Univ Lodz, Lab Biomol Chem, PL-92215 Lodz, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 09期

关键词：

alpha-alkylidene-gamma-lactones; alpha-alkylidene-gamma-lactams; Horner - Wadsworth - Emmons olefination; (1)H; (13)C (31)P NMR; cytotoxic activity;

D O I：

10.1016/j.bmc.2008.03.035

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

A series of 5-aryl-3- alkylidenedihydrofuran-2(3H)-ones 6a - g '' and 11a,b as well as 5-aryl-3- methylidenepyrrolidin-2-ones 10a - c and 12 were synthesized starting from 4-aryl-2-diethoxyphosphoryl-4-oxobutanoates 3a - g. Reaction sequence includes reduction or reductive amination of the carbonyl group, lactonization or lactamization step and finally the Horner - Wadsworth - Emmons olefination of aldehydes using thus obtained 5-aryl-3-diethoxyphosphoryl-3,4-dihydrofuran-2(5H)-ones 5a - g '' or 5-aryl-3-diethoxyphosphorylpyrrolidin-2-ones 9a - c. Furanones 6 and 11, as well as pyrrolidinones 10 and 12, were evaluated in vitro against mouse leukemia cell line L-1210 and two human leukemia cell lines HL-60 and NALM-6. Several of the obtained furanones proved to be very potent against all three cell lines with IC(50) values lower than 6 mu M. Structure - activity relationships of these compounds, as well as 5-alkyl or 5-arylmethyl-3-methylidenedihydrofuran-2(3H)-ones 13a - e, previously obtained in our laboratory, are discussed. (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4872 / 4882

页数：11

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