Studies on the Synthesis, Structure and Biological Activities of Novel Arylaminoformyl-containing 1-Cyano-1-cycloproane Carboxylic Acid Amides Based on Ugi Reaction

doi:10.6023/A15050333

Acta Chim. Sinica ›› 2015, Vol. 73 ›› Issue (11): 1173-1181.DOI: 10.6023/A15050333 Previous Articles Next Articles

Special Issue: 纪念南开大学化学学科创建100周年

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基于Ugi反应的含芳氨基甲酰基1-氰基-1-环丙烷甲酰胺类新化合物的合成、结构和生物活性研究

詹益周, 王宝雷, 张丽媛, 张燕, 张晓, 李正名, 宋海斌

南开大学元素有机化学国家重点实验室天津化学化工协同创新中心天津 300071

投稿日期:2015-05-20 发布日期:2015-11-19
通讯作者: 王宝雷, 李正名 E-mail:nkwbl@nankai.edu.cn;nkzml@vip.163.com
基金资助:
项目受国家自然科学基金面上项目(No. 21372133)和高等学校学科创新引智计划(No. B06005)资助.

Studies on the Synthesis, Structure and Biological Activities of Novel Arylaminoformyl-containing 1-Cyano-1-cycloproane Carboxylic Acid Amides Based on Ugi Reaction

Zhan Yizhou, Wang Baolei, Zhang Liyuan, Zhang Yan, Zhang Xiao, Li Zhengming, Song Haibin

State Key Laboratory of Elemento-Organic Chemistry, Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071

Received:2015-05-20 Published:2015-11-19
Supported by:
Project supported by the National Natural Science Foundation of China (No. 21372133) and “111” Project of Ministry of Education of China (No. B06005).

1. Studies on the Synthesis, Structure and Biological Activities of Novel Arylaminoformyl-containing 1-Cyano-1-cycloproane Carboxylic Acid Amides Based on Ugi Reaction.PDF(53KB)

Abstract

As one of key enzymes that catalyze the biosynthesis of branched-chain amino acids in plants and microorganisms (bacteria, fungi), ketol-acid reductoisomerase (KARI; EC 1.1.1.86) can be regarded as a promising target for designing herbicides or fungicides. Previously, we have found that N-aryl-1-cyano-1-cyclopropane carboxamides and cyclopropylformyl thioureas exhibit favorable KARI inhibitory activity and can be made further structure modification for discovery more new inhibitors. In this continuous work, a series of novel 1-cyano-1-cycloproane carboxylic acid amides containing arylaminoformyl moity 8a～8p were designed accordingly and synthesized via one-pot Ugi reaction with 1-cyano-1-cyclo- propane carboxylic acid, aryl isonitrile, aldehyde and amine as reactants. The structures of the new compounds were confirmed by ¹H NMR, ¹³C NMR, IR spectra and elemental analysis or HRMS. Meanwhile the crystal structure of 8m was reported, which provided comprehensive structure information for this kind of compounds. From a continuous assay method that following the consumption of NADPH (involved in the KARI-catalyzed reaction) at 340 nm, it was found that most of these cyclopropane diamide derivatives exhibit obvious KARI inhibitory activities and are new KARI inhibitors, among which 8a～8c, 8m, 8n and 8j possessed inhibition rate of 94%～98% at a test concentration of 200 mg/L against rice KARI, and 8m had a K_i value of (77.91±30.15) μmol/L. These new inhibitors synthesized in this paper can inhibit KARI enzyme effectively at the same level with those of N-aryl-1-cyano-1-cyclopropane carboxamides reported previously. In addition, the preliminary bioassay results also showed that several compounds exhibit significant in vitro fungicidal activities at a test concentration of 50 mg/L against Ftasarium omysporum, Cercospora arachidicola, Physalospora piricola, Alternaria solani and Gibberella sanbinetti by using the mycelium growth rate test method, and 8e and 8p, which have comparatively broad fungicidal spectrum on the whole and are comparable with the contrast Triadimefon during the present study, could be used as novel hit compounds for further structural optimization in fungicide innovations.

Key words: cyclopropane carboxylic acid amides, Ugi reaction, KARI, fungicidal activity

Cite this article

Zhan Yizhou, Wang Baolei, Zhang Liyuan, Zhang Yan, Zhang Xiao, Li Zhengming, Song Haibin. Studies on the Synthesis, Structure and Biological Activities of Novel Arylaminoformyl-containing 1-Cyano-1-cycloproane Carboxylic Acid Amides Based on Ugi Reaction[J]. Acta Chim. Sinica, 2015, 73(11): 1173-1181.

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基于Ugi反应的含芳氨基甲酰基1-氰基-1-环丙烷甲酰胺类新化合物的合成、结构和生物活性研究

Studies on the Synthesis, Structure and Biological Activities of Novel Arylaminoformyl-containing 1-Cyano-1-cycloproane Carboxylic Acid Amides Based on Ugi Reaction

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[1]	CHEN Pei-Quan^1,2; LIU Xing-Hai^1,2; SUN Hong-Wei^3,4; WANG Bao-Lei^1,2; LI Zheng-Ming*^,1,2,4; LAI Cheng-Ming^2,3. Molecular Simulation Studies of Interactions between Ketol-acid Reductoisomerase and Its Inhibitors [J]. Acta Chimica Sinica, 2007, 65(16): 1693-1701.
[2]	WANG Bao-Lei, WANG Jian-Guo, MA Yi, LI Zheng-Ming*, LI Yong-Hong, WANG Su-Hua. Molecular Docking and 3D-QSAR Research of Amidines of KARI Inhibitor [J]. Acta Chimica Sinica, 2006, 64(13): 1373-1378.