Synthesis of New Chiral γ-Alkoxy-2(5H)-furanone-piperazine-sulfonamide Compounds and Preliminary Evaluation of in Vitro Anticancer Activity

doi:10.6023/cjoc201409008

Chin. J. Org. Chem. ›› 2015, Vol. 35 ›› Issue (2): 439-445.DOI: 10.6023/cjoc201409008 Previous Articles Next Articles

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γ-烷氧基-2(5H)-呋喃酮-哌嗪-磺酰胺类化合物的合成及抗癌活性研究

魏梦雪^a, 高晓慧^a, 张和^a, 李学强^a,b

a 宁夏大学化学化工学院银川 750021;
b 宁夏天然药物工程技术研究中心银川 750021

收稿日期:2014-09-05 修回日期:2014-10-01 发布日期:2014-10-21
通讯作者: 李学强 E-mail:lixq@nxu.edu.cn
基金资助:
国家自然科学基金(Nos. 21462032、21062014)、宁夏大学人才引进科研启动基金(No. 80020241)和宁夏大学“211”工程建设(No. ndzr09-1)资助项目.

Synthesis of New Chiral γ-Alkoxy-2(5H)-furanone-piperazine-sulfonamide Compounds and Preliminary Evaluation of in Vitro Anticancer Activity

Wei Mengxue^a, Gao Xiaohui^a, Zhang He^a, Li Xueqiang^a,b

a School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021;
b Ningxia Engineering Research Center for Natural Medicines, Yinchuan 750021

Received:2014-09-05 Revised:2014-10-01 Published:2014-10-21
Supported by:
Project supported by the National Natural Science Foundation of China (Nos. 21462032, 21062014), the Research Starting Funds for Imported Talents of Ningxia University (No. 80020241), and the “211” Project in Ningxia University (No. ndzr09-1).

1. Synthesis of New Chiral γ-Alkoxy-2(5H)-furanone-piperazine-sulfonamide Compounds and Preliminary Evaluation of in Vitro Anticancer Activity.PDF(1924KB)

Abstract

The enantiomerically pure 5-(S)-5-alkoxy-3,4-dibromo-2(5H)-furanones were readily prepared from furfural through a three-step sequence of bromine-promoted oxidation/acetalization of mucobromic acid with chiral (－)-menthol and (+)-borneol/recrystallization of the resulting γ-butenolides. Then the chiral γ-butenolides were reacted with piperazine through a one-pot two-step protocol combining Michael addition and elimination of hydrogen bromide, resulting in the crude furanone-piperazines, which were further toslated with a range of sulfonyl chlorides. 12 furanone-piperazine-sulfonamide complexs were efficiently obtained in moderate to excellent yields (45.3%～96.2%). All the new compounds were identified by ¹H NMR, ¹³C NMR, IR and HRMS technology. The in vitro anti-tumor activities of these complexs against cervical cancer cell lines (Hela) were evaluated by thiazolylblue (MTT) assay method. Among them, 5-(S)-5-borneolyloxy-4-(p-nitrobenzene-sulfonamide-piperazinyl)-3-bromo-2(5H)-furanone (7k) exhibited the best inhibitory activity with an IC₅₀ of 0.02 μmol/L, providing a new promising lead for further development of new anti-Hela drugs.

Key words: butenolide, furanone-piperazine-sulfonamide, synthesis, Hela cells, anti-tumor activity

Cite this article

Wei Mengxue, Gao Xiaohui, Zhang He, Li Xueqiang. Synthesis of New Chiral γ-Alkoxy-2(5H)-furanone-piperazine-sulfonamide Compounds and Preliminary Evaluation of in Vitro Anticancer Activity[J]. Chin. J. Org. Chem., 2015, 35(2): 439-445.

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γ-烷氧基-2(5H)-呋喃酮-哌嗪-磺酰胺类化合物的合成及抗癌活性研究

Synthesis of New Chiral γ-Alkoxy-2(5H)-furanone-piperazine-sulfonamide Compounds and Preliminary Evaluation of in Vitro Anticancer Activity

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