5-(1-氨基-2-苯氧亚乙基)巴比妥酸衍生物的合成及除草活性研究

doi:10.6023/cjoc202010042

有机化学 ›› 2021, Vol. 41 ›› Issue (5): 2063-2073.DOI: 10.6023/cjoc202010042 上一篇下一篇

研究论文

5-(1-氨基-2-苯氧亚乙基)巴比妥酸衍生物的合成及除草活性研究

王超超, 刘会, 赵微, 李攀, 冀庐莎, 柳仁民, 雷康^*(), 徐效华

a 聊城大学药学院山东聊城 252000
b 聊城大学生命科学学院山东聊城 252000
c 南开大学元素有机化学国家重点实验室天津 300071

收稿日期:2020-10-30 修回日期:2020-11-25 发布日期:2021-02-22
通讯作者: 雷康
作者简介:
† 共同第一作者.
基金资助:
国家自然科学基金(31701827); 中国博士后科学基金(2020M671984); 聊城大学博士科研启动基金(318051647); 聊城大学大学生创新创业训练(CXCY2020Y179); 山东省自然科学基金(ZR2019PC041)

Synthesis and Herbicidal Activity of 5-(1-Amino-2-phenoxyethylidene)barbituric Acid Derivatives

Chaochao Wang, Hui Liu, Wei Zhao, Pan Li, Lusha Ji, Renmin Liu, Kang Lei^*(), Xiaohua Xu

a School of Pharmacy, Liaocheng University, Liaocheng 252000
b College of Life Sciences, Liaocheng University, Liaochen 252000
c State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071

Received:2020-10-30 Revised:2020-11-25 Published:2021-02-22
Contact: Kang Lei
About author:
* Corresponding author. E-mail: leikang@lcu.edu.cn
† These authors contributed equally to this work.
Supported by:
National Natural Science Foundation of China(31701827); China Postdoctoral Science Foundation(2020M671984); Doctoral Research Startup Foundation of Liaocheng University(318051647); Innovation and Entrepreneurship Training Program for College Students of Liaocheng University(CXCY2020Y179); Natural Science Foundation of Shandong Province(ZR2019PC041); National Natural Science Foundation of China(21675071)

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摘要/Abstract

基于具有生物活性的烯胺二酮骨架及前期报道的先导化合物5-酰基巴比妥酸I的结构, 设计、合成了26个结构新颖的5-(1-氨基-2-苯氧亚乙基)巴比妥酸衍生物. 生物活性测试结果表明, 化合物5-(2-(2-氯-4-氟苯氧基)-1-(戊基氨基)亚乙基)-1,3-二甲基嘧啶-2,4,6(1H,3H,5H)-三酮(APB-5)在苗后处理, 187.5 g?ha^–1剂量时, 对双子叶植物(油菜、苋菜)具有100%的抑制活性. 更重要的是, 化合物APB-5在375 g?ha^–1的剂量时具有宽的除草谱且对玉米、小麦和谷子安全, 这说明该化合物具有成为除草剂的潜力. 此外, 通过研究拟南芥的表型及化合物对激素响应基因的影响发现, 化合物APB-5具有与激素类除草剂2,4-二氯苯氧乙酸(2,4-D)相似的作用机制. 目前的研究表明, 化合物APB-5可以作为进一步开发新型生长素类除草剂的先导结构.

关键词: 巴比妥酸, 烯胺二酮, 合成, 除草活性, 激素

Based on the bioactive enamino diketone skeleton and the structure of our previously reported lead compound 5-acylbarbituric acid I, twenty-six novel 5-(1-amino-2-phenoxyethylidene)barbituric acid derivatives were designed and synthesized. The bioassay results showed that the analog 5-(2-(2-chloro-4-fluorophenoxy)-1-(pentylamino)-ethyli- dene)-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (APB-5) displayed excellent post-emergent herbicidal activity, with inhibition 100% against dicotyledonous plants (Brassica campestris, Amaranthus retroflexus), even at a dosage of 187.5 g? ha^–1. More importantly, compound APB-5 showed a broad spectrum of weed control and displayed good crop safety toward wheat, maize and millet, when applied at 375 g?ha^–1, indicating its remarkable potential as a herbicide. Furthermore, by investigating the phenotypes of Arabidopsis thaliana and analyzing the effect of compound APB-5 on auxin response genes in plants, it was found that compound APB-5 had a herbicidal mechanism similar to auxin-type herbicides, such as 2,4-dichlorophenoxyacetic acid (2,4-D). Taken together, the present work demonstrated that compound APB-5 could serve as a lead structure for further developing novel auxin-type herbicides.

Key words: barbituric acid, enamino diketone, synthesis, herbicidal activity, auxin

引用此文

王超超, 刘会, 赵微, 李攀, 冀庐莎, 柳仁民, 雷康, 徐效华. 5-(1-氨基-2-苯氧亚乙基)巴比妥酸衍生物的合成及除草活性研究[J]. 有机化学, 2021, 41(5): 2063-2073.

Chaochao Wang, Hui Liu, Wei Zhao, Pan Li, Lusha Ji, Renmin Liu, Kang Lei, Xiaohua Xu. Synthesis and Herbicidal Activity of 5-(1-Amino-2-phenoxyethylidene)barbituric Acid Derivatives[J]. Chinese Journal of Organic Chemistry, 2021, 41(5): 2063-2073.

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图/表 8

Figure 1. Design of target compound APB by using compound I as lead compound

Scheme 1. Synthetic route of preparing target compounds APB-1~APB-26

Figure 2. X-Ray crystal structure of compound APB-10

Figure 3. Effects (% inhibition) of compounds APB-1 to APB-26 on loss of plant weight at a dosage of 1500 g?ha–1 (a) pre-emergence condition; (b): post-emergence condition; BC: Brassica campestris; AR: Amaranthus retroflexus; EC: Echinochloa crusgalli; DS: Digitaria sanguinalis.

Figure 4. Photographs illustrating seedling and root phenotype of A. thaliana (A) and effect of APB-5, atrazine and 2,4-D on the expression levels of IAA5, GH3.3 and AUX1 (B) Error bars represent standard deviation from three biological replicates.

Figure 5. Herbicidal spectrum testing of compound APB-5 under pre-emergence conditions at a dosage of 375 g?ha-1 Abbreviation: BC, Brassica campestris; AR, Amaranthus retroflexus; PO, Portulaca oleracea; AM, Abutilon theophrasti Medicus; ID, Ixeris denticulate; CA, Chenopodium album; EC, Echinochloa crusgalli; DS, Digitaria sanguinalis; AF, Avena fatua; EI, Eleusine indica; PD, Puccinellia distans; CV,Chloris virgate

Compd.	Rate/(g?ha^–1)	B. campestris		A. retroflexus		E. crusgalli		D. sanguinalis
Compd.	Rate/(g?ha^–1)	Pre	Post	Pre	Post	Pre	Post	Pre	Post
APB-5	750	100	100	100	100	93.2±2.0	33.3±2.4	55.1±1.3	20.2±1.7
	375	94.4±3.0	100	100	100	73.2±1.7	5.1±0.8	26.8±2.7	4.6±1.1
	187.5	77.1±2.3	100	93.1±2.9	100	49.6±2.5	0	17.0±1.8	0
2,4-D	750	100	100	100	100	100	43.8±2.9	92.4±2.1	50.0±1.9
	375	90.5±1.2	100	100	100	69.7±3.3	20.4±2.0	66.1±1.0	9.9±2.1
	187.5	41.4±2.6	100	92.4±1.8	100	55.5±1.1	9.9±3.7	17.3±2.6	0

Table 1. Effects (inhibition/%) of compound APB-5 on loss of plant weight at lower dosage in greenhouse testinga

Compd.	Injury/%
Compd.	Wheat	Mazie	Cotton	Millet	Peanut
APB-5	0	0	45.2±2.6	0	33.3±2.1
2,4-D	0	0	0	21.3±2.6	24.5±1.3

Table 2. Pre-emergence crop safety of compound APB-5 (injury inhibition)a

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5-(1-氨基-2-苯氧亚乙基)巴比妥酸衍生物的合成及除草活性研究

Synthesis and Herbicidal Activity of 5-(1-Amino-2-phenoxyethylidene)barbituric Acid Derivatives

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