摘要：
Harmful cyanobacteria bloom (HCB) has occurred frequently in recent years and it is urgent to develop novel algicides to deal with this problem. In this paper, a series of novel thiamin diphosphate (ThDP) analogs 5a-5g were designed and synthesized targeting cyanobacterial pyruvate dehydrogenase complex E1 (Cy-PDHc E1). Our results showed that compounds 5a-5g have higher inhibitory activities against Cy-PDHc E1 (IC50 9.56-3.48microM) and higher inhibitory activities against two model cyanobacteria strains Synechocystis sp PCC6803 (EC50 2.03-1.58microM) and Microcystis aeruginosa FACHB905 (EC50 1.86-0.95microM). Especially, compound 5b displayed highest inhibitory activities (IC50=3.48microM) against Cy-PDHc E1 and powerful inhibitory activities against cyanobacteria Synechocystis sp PCC6803 (EC50=1.58microM) and Microcystis aeruginosa FACHB905 (EC50=1.04microM). Moreover, the inhibitory activities of compound 5b were even higher than those of copper sulfate (EC50=2.02 and 1.71microM separately) which has been widely used as algicide against cyanobacteria PCC6803 and FACHB905. The more important was that compound 5b display much higher inhibitory selectivity between Cy-PDHc E1 (Inhibitory rate 97.4%) and porcine PDHc E1 (Inhibitory rate 11.8%) under the same concentration (100muM). The inhibition kinetic experiment and molecular docking research showed that compound 5b can inhibit Cy-PDHc E1 by occupying the ThDP-binding pocket and then blocking Cy-PDHc E1 bound to ThDP as competitive inhibitor. The imagines of SEM and TEM showed that cellular microstructures were heavily destroyed under compound 5b stress. Our results demonstrated compound 5b could be taken as a potential lead compound targeting Cy-PDHc E1 to obtain environment-friendly algicide for harmful cyanobacterial blooms control.
摘要：
Cyanobacteria harmful algal blooms are of global concern, but all currently available algicides in the market are nonselective and have potential side effects on nontarget species. In the present work, two series of compounds (4 and 6) comprising 16 novel 1,2,3-triazole aminopyrimidines were rationally designed and synthesized as control agent for cyanobacteria. Our design focus was the inhibiting cyanobacteria by inhibition against pyruvate dehydrogenase complex E1 (PDHc-E1). Compounds 4 and 6 showed potent inhibition against Escherichia coli PDHc-E1 (IC50 = 4.13-23.76 muM) and also strong algicidal activities against Synechocystis sp. PCC 6803 (EC50 = 1.7-8.1 muM) and Microcystis sp. FACHB905 (EC50 = 2.1-11.8 muM). In particular, the algicidal activities of 6d against four algal species were not only higher than that of prometryn; they were also comparable to or higher than that of copper sulfate. The analogues 4c, 4d, 6d, and 6e displayed potent algicidal activities and inhibition of E. coli PDHc-E1 but exhibited negligible inhibition of porcine PDHc-E1. As revealed by molecular docking, site-directed mutagenesis, enzymatic assays, and an inhibition kinetic analysis, 4c and 6d inhibited PDHc-E1 in a competitive manner. Our results suggest that highly selective, effective algicides can be developed by rationally designing competitive PDHc-E1 inhibitors.
作者机构：
[王婷婷; 高新蕾] College of Chemical and Environmental Engineering, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China;[彭浩] Key Laboratory of Pesticides and Chemical Biology, Central China Normal University, Wuhan, Hubei, 430079, China;[王展] College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan, Hubei, 430023, China;[戴康] College of Pharmacy, South-Central University for Nationalities, Wuhan, Hubei, 430074, China
通讯机构：
College of Chemical and Environmental Engineering, Wuhan Polytechnic University, Wuhan, Hubei, China
期刊：
Journal of Chemical Information and Modeling,2017年57(6):1426-1438 ISSN：1549-9596
通讯作者：
Ren, Yanliang;Wan, Jian
作者机构：
[Feng, Lingling; Zhu, Shuaihua; Wan, Fen; Rao, Li; Wei, Lin; Hong, Zongqin; Ren, Yanliang; Wan, Jian; Zhu, Xiuyun; Han, Xinya; Peng, Hao] Cent China Normal Univ, Dept Chem, Minist Educ, Int Cooperat Base Pesticide & Green Synth Hubei,K, Wuhan 430079, Peoples R China.;[Guo, Li] Hubei Environm Monitoring Cent Stn, Wuhan 430072, Hubei, Peoples R China.
通讯机构：
[Ren, YL; Wan, J] C;Cent China Normal Univ, Dept Chem, Minist Educ, Int Cooperat Base Pesticide & Green Synth Hubei,K, Wuhan 430079, Peoples R China.
摘要：
Based on our previous work on the structural modification of the lead compound I, three series of novel fluorine-containing phosphonates derivatives (II, III and IV) were designed and synthesized. Their post-emergence herbicidal activities against some species of weeds were evaluated in a green house. The compounds II were synthesized by introducing of two methylene into the structure I. Compared with the commercial herbicidal clacyfos, compounds II showed moderate herbicidal activity with 60–85% inhibition effect against chingma abutilon (Abutilon theophrasti), common amaranth (Amaranthus retroflexus) and white eclipta (Eclipta prostrate) at a rate of 150 g ai/ha. The compounds III were designed by introducing open-chain phosphonates, which displayed notable herbicidal activity. Especially, the compounds III-1–III-4, III-6, III-8, III-11 and III-12 exhibited significant herbicidal activity (80–100%) comparing to the clacyfos against all tested broadleaf weeds, while compounds IV with five carbon atoms in the carboxylic acid chain were inactive against all of the tested weeds. Structure-activity relationship analyses indicated that the length of the carbon chain had a great effect on the herbicidal activity. Furthermore, a broad spectrum test confirmed that compounds III-4 and III-8 were comparable with glyphosate against all of the tested weeds at a rate of 75 g ai/ha.
期刊：
Chinese Journal of Structural Chemistry,2016年35(6):857-862 ISSN：0254-5861
通讯作者：
Peng Hao
作者机构：
[Peng Hao] Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.;Cent China Normal Univ, Coll Chem, Wuhan 430079, Peoples R China.
通讯机构：
[Peng Hao] C;Cent China Normal Univ, Minist Educ, Key Lab Pesticide & Chem Biol, Wuhan 430079, Peoples R China.
摘要：
A new crystal of (E)-2-(2,4-dichlorophenoxy)-l-(5,5-dimethyl-2-oxido-1,3.2-dioxa-phosphinan-2-yl)vinyl 2-(2,4-dichlorophenoxy)acetate has been determined by single-crystal X-ray diffraction. The compound crystallizes in triclinic, space group P1 with a = 7.9393(17),b = 11.974(3) A,c = 13.532(3) A, a = 90.937(4),β=101.998(3),y = 101.363(4)°,V= 1231.5(5) A~3, D_c =1.500 Mg/m~3, Z = 2,F(000) = 568 and μ = 0.585 mm~(-1). The molecular packing in the crystal is the result of C(10)-H(10)...O(5) hydrogen bond, as well as weak π-π stacking interactions. The herbicidal activity results indicated that the title compound 3 showed 80~100% inhibitory activities against all of the tested weeds at a dosage of 150 g-ai/ha.
摘要：
On the basis of previous study on 2-methylpyrimidine-4-ylamine derivatives I, further synthetic optimization was done to find potent PDHc-E1 inhibitors with antibacterial activity. Three series of novel pyrimidine derivatives 6, 11 and 14 were designed and synthesized as potential Escherichia coli PDHc-E1 inhibitors by introducing 1,3,4-oxadiazole-thioether, 2,4-disubstituted-1,3-thiazole or 1,2,4-triazol-4-amine-thioether moiety into lead structure I, respectively. Most of 6, 11 and 14 exhibited good inhibitory activity against E. coli PHDc-E1 (IC50 0.97-19.21 mu M) and obvious inhibitory activity against cyanobacteria (EC50 0.83-9.86 mu M). Their inhibitory activities were much higher than that of lead structure I. 11 showed more potent inhibitory activity against both E. coli PDHc-E1 (IC50 < 6.62 mu M) and cyanobacteria (EC50 < 1.63 mu M) than that of 6, 14 or lead compound I. The most effective compound 11d with good enzyme-selectivity exhibited most powerful inhibitory potency against E. coli PDHc-E1 (IC50 = 0.97 mu M) and cyanobacteria (EC50 = 0.83 mu M). The possible interactions of the important residues of PDHc-E1 with title compounds were studied by molecular docking, site-directed mutagenesis, and enzymatic assays. The results indicated that 11d had more potent inhibitory activity than that of 14d or I due to its 1,3,4-oxadiazole moiety with more binding position and stronger interaction with Lsy392 and His106 at active site of E. coli PDHc-E1. (C) 2016 Elsevier Ltd. All rights reserved.
通讯机构：
[Chen, J; Yu, GA] C;Cent China Normal Univ, Coll Chem, Key Lab Pesticide & Chem Biol, Minist Educ, Wuhan 430079, Peoples R China.
摘要：
An air-stable aryl substituted indenyl phosphine used in combination with Pd(OAc)(2) provides a highly efficient catalyst for the Suzuki-Miyaura cross-coupling reaction of sterically hindered aryl halides with aryl boronic acids.
摘要：
[目的]为了获得具有除草剂应用价值的高活性化合物。[方法]以烃基膦酸酯为先导结构,对其含磷端以及桥链和芳基部分进行结构修饰,设计合成多个系列烃基膦酸酯类化合物。[结果]除草活性测试结果表明,在150 g ai/ha剂量下,多个化合物对芥菜、苘麻、反枝苋和醴肠等阔叶杂草表现出良好的抑制活性,除草活性与对照药剂氯酰草膦相当甚至更优。杀草谱测试结果表明数个化合物对阔叶杂草的防效与草甘膦相当。作物安全性评
摘要：
GRAPHICAL ABSTRACT Synthesis and fungicidal activity of aryl(arylamino)methylphosphonic acids All authors Haiqin Wang, Hao Peng & Hongwu He https://doi.org/10.1080/10426507.2015.1119829 Published online:11 May 2016 ABSTRACT A series of aryl(arylamino)methylphosphonic acids were synthesized based on the previous work for the modification of alkylphosphonates. As key intermediates, α-aminophosphonates were synthesized with high yield by a three-component Kabachnik–Fields reaction under solvent-free conditions. The compounds were identified and characterized by infrared, 1H NMR, 13C NMR, mass spectrum, and elemental analyses. Their fungicidal activities against typical fungi occurring in the Chinese agro-ecosystems were evaluated. The results of preliminary bioassays showed that some of the title compounds exhibited moderate fungicidal activities against tomato late blight and cucumber fusarium wilt. For example, compound 3b showed 78% inhibitory activity against tomato late blight, and compound 3h possessed 86% inhibitory activity against cucumber fusarium wilt.
