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

doi:10.6023/cjoc202010042

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (5): 2063-2073.DOI: 10.6023/cjoc202010042 Previous Articles Next Articles

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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

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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Abstract

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

Cite this article

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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Fig. & Tab. 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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