Synthesis of 2-amino-6-oxocyclohexenylsulfonamides and their activity against Botrytis cinerea

BACKGROUND: With the objective of exploring the fungicidal activity of 2‐oxocyclohexylsulfonamides (2), a series of novel 2‐amino‐6‐oxocyclohexenylsulfonamides (6 to 23) were synthesised, and their fungicidal activities against Botrytis cinerea Pers. were evaluated in vitro and in vivo. RESULTS: The compounds were characterised by IR, ¹H NMR and elemental analysis. Bioassay results of mycelial growth showed that compounds 6 to 23 had a moderate antifungal activity against B. cinerea. N‐(2‐methylphenyl)‐2‐(2‐methylphenylamino)‐4,4‐dimethyl‐6‐oxocyclohexenylsulfonamide (13) and N‐(2‐chlorophenyl)‐2‐(2‐chlorophenylamino)‐6‐oxocyclohexenylsulfonamide (21) showed best antifungal activities, with EC₅₀ values of 8.05 and 10.56 µg mL^?1 respectively. Commercial fungicide procymidone provided an EC₅₀ value of 0.63 µg mL^?1. The conidial germination assay showed that most of compounds 6 to 23 possessed excellent inhibition of spore germination and germ‐tube elongation of conidia of B. cinerea. For in vivo control of B. cinerea colonising cucumber leaves, the compound N‐cyclohexyl‐2‐(cyclohexylamino)‐4,4‐dimethyl‐6‐oxocyclohexenylsulfonamide (19) showed a better control effect than the commercial fungicide procymidone. CONCLUSION: The present work demonstrated that 2‐amino‐6‐oxocyclohexenylsulfonamides can be used as possible new lead compounds for further developing novel fungicides against B. cinerea. Copyright © 2011 Society of Chemical Industry     

新型N-芳基-2-((5-((4,6-二甲基嘧啶-2-基)硫甲基)-1,3,4-噻二唑-2-基)硫)乙酰胺类化合物的合成及杀菌活性

为寻找新型杂环活性化合物,通过活性亚结构拼接,以硫脲和乙酰丙酮为起始原料合成4,6-二甲基嘧啶-2-硫醇,随后经酯化、肼化、环化和缩合反应,设计并采用微波辅助合成了10个新型N-芳基-2-（（5-（（4,6-二甲基嘧啶-2-基）硫甲基）-1,3,4-噻二唑-2-基）硫）乙酰胺类化合物,其结构通过核磁共振氢谱和碳谱、红外光谱、质谱及元素分析确认。初步生物活性测试结果表明,在50 mg/L下,大部分目标化合物对植物病原真菌具有一定的抑制活性,其中化合物8h对黄瓜炭疽病菌Colletotrichum orbiculare的抑制率达77.3%。     

Design, synthesis, insecticidal activity and structure-activity relationship of 3,3-dichloro-2-propenyloxy-containing phthalic acid diamide structures

BACKGROUND: Phthalic acid diamide derivatives are among the most important classes of synthetic insecticides. In this study, a 3,3‐dichloro‐2‐propenyloxy group, the essential active group of pyridalyl derivatives, was incorporated into phthalic acid diamide derivatives with the aim of combining the active groups to generate more potent insecticides. RESULTS: Thirty‐one new phthalic acid diamides were obtained, and these were characterised by ¹H and ¹³C NMR. The structure of N²‐[1,1‐dimethyl‐2‐(methoxy)ethyl]‐3‐iodo‐N¹‐[4‐(3,3‐dichloro‐2‐propenyloxy)‐3‐(trifluoromethyl)phenyl]‐1,2‐benzenedicarboxamide was determined by X‐ray diffraction crystallography. The insecticidal activities of the compounds against Plutella xylostella were evaluated. The title compounds exhibited excellent larvicidal activities against P. xylostella. Structure‐activity relationships revealed that varying the combination of aliphatic amide and aromatic amide moieties, or the nature and position of substituent Y on the aniline ring, could aid the design of structures with superior performance. CONCLUSION: A series of novel phthalic acid diamides containing a 3,3‐dichloro‐2‐propenyloxy group at the 4‐position of the aniline ring were designed and synthesised. Structure‐activity relationships with the parent structure provided information that could direct further investigation on structure modification. Copyright © 2012 Society of Chemical Industry     

Structural Effects of N-Arylcarbamoylpyrazolines on Calcium Uptake in Rat Brain Synaptosomes

N-Arylcarbamoylpyrazolines with various substituents at the para position of the carbamoyl benzene ring inhibited ATP-dependent Ca²⁺-uptake in synaptosomes prepared from the rat brain. The activity of these compounds was evaluated as log(1/I₅₀), the reciprocal logarithm of half inhibitory concentration, I₅₀ (m ), from the concentration–response curve for the inhibition of Ca²⁺-uptake. Among the compounds tested, methyl 3-(4-chlorophenyl)-4-methyl-1-[N-(4-trifluoromethylphenyl)carbamoyl]-2-pyrazoline-4-carboxylate was the most potent, the I₅₀ value of which as 9·12×10⁻⁷ m . Variations in the activity in terms of log(1/I₅₀) were quantitatively analysed using a substituent parameter, showing that the higher the electron-withdrawing effect of the substituent, the higher was the activity. The substituent effects were similar to those on insecticidal activity against the Americal cockroach. The higher the inhibitory activity against Ca²⁺ uptake, the higher seemed to be the insecticidal activity. Methyl(4S) - 3 - (4 - chlorophenyl) - 4 - methyl - 1 - [N - (4 - chlorophenyl)carbamoyl] - 2 - pyrazoline -4-carboxylate had higher inhibitory activity against Ca²⁺-uptake and higher in-secticidal activity than the R-isomer, but the difference was greater in theCa²⁺-uptake system.     

Fungicidal activity of N-(2-cyano-2-methoximinoacetyl)amino acids and their derivatives

More than 20 N-(2-cyano-2-methoximinoacetyl)amino acids and derivatives were synthesised and tested for antifungal activity against grape downy mildew, caused by Plasmopara viticola (de Bary) Berl. & de Toni, and rape downy mildew, Peronospora parasitica Fr. Two of the compounds containing a free carboxylic acid group, a moiety which has been shown to confer phloem mobility on compounds, showed high activity, especially against P. parasitica, in protectant tests. These results indicate that there is no incompatibility between the acid function and fungicidal activity. A number of the esters showed activity comparable with that of cymoxanil in the protectant tests, and the tert-butyl esters of the methionine derivative and its sulfone were more than ten times as active as the commercial compound.     

The antifungal activity of some sulphonyl derivatives of isoxazole,pyrazole, thiazole and thiophene

Fifty-three heterocyclic sulphonyl derivatives including eight sulphonamides, three sulphonyl azides, nine sulphonohydrazides and twenty sulphonohydrazones of substituted thiophenes, and a smaller range of analogous isoxazoles pryazoles and thiazoles, were tested as potential fungicides in a simple screening procedure against Mucor mucedo, Septoria nodorum, Trichoderma viride, Chaetomium globosum and Aspergillus niger. Several thiophene-2-sulphonyl based compounds exhibited a high level of antifungal activity at 100 mg litre^?1 against the five test species, especially the mono-halogen-substituted sulphonamides and sulphonohydrazines, in which a single chlorine or bromine atom was substituted in the para position of an attached phenyl ring. The most active compound, against all five species of fungus was N-(4-chlorophenyl)-N-(trichloromethylthio) thiophene-2-sulphonamide which had average MIC₅₀ and MIC₁₀₀ values of 86 and 180 μmol respectively. (MIC₅₀ and MIC₁₀₀ values are, respectively, the concentrations required to inhibit fungal growth by 50% and to inhibit it totally.) In general, the isoxazole analogues of the thiophene-2-sulphonyl compounds exhibited a much lower fungitoxic activity, whilst the pyrazole and thiazole based compounds had little or no activity. Compared with the other results, the considerable activity shown by 4-[2′-(3,4-dichlorobenzylidene)hydrazinosulphonyl]thiophene-2-carboxylic acid was unexpected.     

新型腙类衍生物的合成及其生物活性

利用3-(N-甲基-N-甲氧基氨基)-1-芳基-1-丙酮腙与酰氯反应,合成了14个新型N-酰基-3-(N-甲基-N-甲氧基氨基)-1-芳基-1-丙酮腙化合物,其化学结构经1H核磁共振和元素分析确证。初步的生物活性测试结果表明,部分化合物在50 mg/L时对淡色库蚊Culex pipiens pallens的致死率为95%~100%;化合物 c7 在1 000 mg/L时对粘虫Leucania separata Walke 的致死率达100%。     

10种N-取代氨基香豆素的合成及生物活性

基于结构拼接思想,设计合成了10个N-取代氨基香豆素类化合物,并测定了其抑菌及除草活性。6-硝基香豆素经Fe/NH4Cl还原得6-氨基香豆素,再与不同醛缩合得Schiff碱,最后经硼氢化钠还原制得10个N-取代氨基香豆素类化合物(4a~4J),其中9个未见文献报道,其结构均经红外光谱、核磁共振氢谱和质谱确认。抑菌活性测试结果表明,所有化合物对苹果腐烂病菌Valsa mali、葡萄白腐病菌Coniothyrium diplodiella、棉花枯萎病菌Fusarium oxysporium和柑橘炭疽病菌Citrusanthrax bacteria均有一定抑制作用,其中 4e 的抑菌活性最强,对苹果腐烂病菌和柑橘炭疽病菌的EC50值分别为7.53和12.93 mg/L,对其余2种植物病原菌的EC50值均小于25 mg/L;化合物 4f 次之,对苹果腐烂病菌和葡萄白腐病菌的EC50值均约为11 mg/L。除草活性测试结果表明,除 4f 外,所有目标化合物均有一定除草作用,其中 4c 的活性最强,100 mg/L下对反枝苋Amaranthus retroflexus种子根、茎生长的抑制率均为99%。     

1-(2-酰氧基-4,5-亚甲二氧基)苯基-2-甲基丙烯酮类化合物的合成及抑菌活性

以具有较高抑菌活性的卡枯醇衍生物1-(2-羟基-4,5-亚甲二氧基)苯基-2-甲基丙烯酮为原料,设计合成了14个未见文献报道的1-(2-酰氧基-4,5-亚甲二氧基)苯基-2-甲基丙烯酮类(2a～2n)化合物,其结构经电喷雾串联质谱(ESI-MS)和核磁共振氢谱确证。初步生物活性测试结果表明,在100 mg/L下,目标化合物对5种供试病原菌均具有较高的抑菌活性,其中, 2b和2d 对番茄灰霉病菌Botrytis cinerea和小麦赤霉病菌Fusarium graminearum的抑制率达100%。     

含5-苯基2-呋喃环的3(2H)哒嗪酮类衍生物的合成与生物活性(I)(英文)

为探索新的农药先导化合物,经取代苯基呋喃甲酰氯与5-肼基-3(2H)哒嗪酮反应,得到15个未见文献报道的含呋喃环3(2H)哒嗪酮类化合物,其结构均通过了红外光谱、核磁共振氢谱和元素分析确认。初步生物活性测定结果表明,目标化合物具有良好的杀菌活性,但杀虫活性较弱。其中化合物3k在50 mg/L时对灰霉病菌的抑制率为86.29%±1.51%,与对照药剂腐霉利相当。初步的构效关系研究结果显示,苯环上取代基的种类和位置对杀菌活性有重要影响。     

Synthesis and fungicidal activity of N-(p-sulfonylphenyl)-N1 -carbamoylureas

A series of 11 N-(p-sulfonylphenyl)-N¹-carbamoylureas was prepared by reaction of 1,6-diphenyl-2,4-dioxohexahydro-s-triazine with chlorosulfonic acid and thionyl chloride. The resultant N-(p-chlorosulfonylphenyl)-N¹-carbamoylurea was subsequently condensed with amines, butanol, hydrazine and sodium azide. The hydrazide was reacted with carbonyl compounds and the azide with trimethyl phosphite. The products were tested for in-vivo fungicidal activity against barley powdery mildew (Erysiphe graminis); the acetone hydrazone derivative showed the highest activity. © 1998 SCI.     

Synthesis and Mosquito Repellent Properties of 2,2-Dialkyl- and 2-Alkyl-4,4-dimethyl-N-acetyloxazolidines

Nineteen novel N-acetyl-2,2-dialkyloxazolidines ( 2 ) and N-acetyl-2-alkyl-4,4-dimethyloxazolidines ( 3 ) were synthesized from commercially available carbonyl compounds and ethanolamine or 2-amino-2-methyl-1-propanol. Their bioactivity against laboratory-reared mosquitoes was compared in patch tests to known N-acetyl-2-alkyloxazolidines ( 1 ) and N,N-diethyl-m-toluamide (deet insect repellent). Isomeric composition measurements by [¹³C]NMR spectroscopy favoured the Z rotational isomer for samples of 2 (91–96% Z) and the E rotational isomer for samples of 3 (66–71% E), in agreement with molecular mechanics calculations on rotational isomers of model oxazolidines. Samples of 1 were previously shown to exist in solution mostly as the Z isomer (60–70% Z). Within the optimal molecular weight range for these experimental chemicals, the duration of repellency against Aedes aegypti (L.), Anopheles quadrimaculatus Say and Anopheles albimanus Wiedemann generally followed the order: 1 > 2 >deet> 3 . Bioassay data are discussed in relation to the equilibrium populations of rotational isomers for substituted N-acetyloxazolidines.     

Fungicidal activity of a series of chloroacetylanilidophosphonates

Nine diethyl chloroacetylanilidomethylphosphonates and ten diethyl α-(chloroacetylanilido)benzylphosphonates were prepared by N-chloroacetylation of the corresponding diethyl anilinomethyl- and anilinobenzylphosphonates. These were tested for antifungal activity against six phytopathogenic fungi. Most of the compounds showed moderate protective properties. No significant difference in activity was observed for compounds with an extra aryl ring substituent on the methylene group of the backbone. Compounds with electron-withdrawing substituents, especially chlorine, on the aniline site (R¹) showed higher fungicidal activity than the other compounds with electron-donating groups as substituents.     

N-(2-三氟甲基-4-氯苯基)-2-吡唑酰氨基环己烷基磺酰胺类化合物的合成与杀菌活性

吡唑酰胺类杀菌剂是近年新农药开发的热点。本研究采用EDCI/HOBt酰胺化法合成了14个结构新颖的N-(2-三氟甲基-4-氯苯基)-2-吡唑酰氨基环己烷基磺酰胺类化合物 ( 3a ~ 3n ),其结构均经1H NMR、13C NMR、质谱和元素分析确认,并用X-射线衍射法确定了化合物 3g 的单晶结构和立体构型。菌丝生长速率法试验结果表明,化合物 3a 、 3e 和 3j 对番茄灰霉病菌Botrytis cinerea KZ-9的EC₅₀值分别为4.28、10.08和11.31 mg/L,抑菌活性不及对照药剂啶酰菌胺和腐霉利;但在孢子萌发试验中,目标化合物表现出与对照药剂相近的抑菌活性,在10 mg/L下有7个化合物对灰霉病菌孢子萌发的抑制率超过了85%;在番茄活体盆栽试验中,化合物 3e 在200 mg/L下对番茄叶片及其花上灰霉病菌的防治效果分别为77.5%和65.2%,高于对照药剂啶酰菌胺 (防效分别为59.8%和30.3%),有进一步研究的价值。     

N-取代苯基-2-(苯并异噻唑啉-3-酮-2-基)甲酰胺的合成及抑菌活性

通过取代苯异氰酸酯与1,2-苯并异噻唑啉-2(3H)-酮(BIT)反应,制备了13个2-(苯并异噻唑啉-3-酮-2-基)甲酰胺类化合物,其中9个未见文献报道。所有化合物的结构均经IR、1H NMR和元素分析确认。初步的抑菌活性测定结果表明,部分目标化合物对供试病原菌具有很好的抑菌活性,尤其对于枯草芽孢杆菌Bacillus subtilis和芒果蒂腐病菌Botryodiplodia theobromae,大部分化合物在50 mg/L下的抑制率在80%~100%之间。     

The Synthesis and Insecticidal Activity of a Series of 2-Aryl-1,2,3-triazoles

Two synthetic routes to 2-aryl-1,2,3-triazoles are outlined. These have been used to synthesise a wide range of compounds of this structural type. Their insecticidal activities were evaluated against a number of veterinary and public health pests. The activity of these compounds is especially good against the housefly (Musca domestica). Structure–activity relationships are discussed particularly in relation to the physical properties of the compounds.     

2-氧代-2-苯基乙磺酰胺化合物组合合成与杀菌活性研究

为了快速获得具有高效杀菌活性的先导化合物,利用组合化学与传统合成方法相结合的方案,研究了N-取代-2-氧代-2-苯基乙磺酰胺类化合物对灰霉病菌的杀菌活性。首先以苯乙酮为原料,经过磺化、氯化反应,制备得到2-氧代-2-苯基乙磺酰氯,再分别与苯胺、苄胺和烷基胺组合库反应,制备了33个组合库,其中包含105个化合物,收率在60%~90%之间,纯度在70%~95%之间。筛选其中的10个活性库进行平行合成,得到29个化合物,又对其中10个活性化合物进行了纯化与结构鉴定。最后用灰霉病菌Botrytis cinerea对所有组合库与化合物进行离体与活体双重筛选,快速确定了高活性先导化合物,为进一步的结构优化奠定了基础。     

2-[4-(对氟苯基)噻唑-2-基]-3-羟基-3-烃氧基丙烯腈的合成及杀菌活性

为了寻找生物活性良好的噻唑基丙烯腈类化合物,利用2-氰甲基-4-(对氟苯基)噻唑( 3 )与取代氯甲酸酯( 4 )在碱存在下反应,合成了15个未见文献报道的2- -3-羟基-3-烃氧基丙烯腈化合物( 5 ),其结构经核磁共振氢谱、质谱和元素分析表征。初步杀菌活性测试结果表明:所有化合物在试验浓度下均具有一定的抑菌活性,尤其对炭疽病菌Colletotrichum gossypii表现出较好的抑制活性,在质量浓度25 mg/L下,所有化合物的抑制率均在50%以上,其中化合物 5a、5e、5g、5k、5n和5o 的抑制率在80%以上。     

2-取代苯并咪唑类化合物的合成及其抑菌活性

以甲基酮、草酸二乙酯或草酸二甲酯、盐酸羟胺和水合肼为原料,通过缩合、环合、水解等反应,将取代吡唑环、异 NFDA1 唑环引入苯并咪唑的2位,设计合成了13个未见文献报道的2-取代苯并咪唑类衍生物,其结构经红外、电喷雾串联质谱(ESI-MS)和核磁共振氢谱确证。初步生物活性测试结果表明,在100 mg/L质量浓度下,所有目标化合物对6种供试病原菌均具有一定的抑菌活性,其中2-吡唑取代的化合物 2a~2d 对苹果炭疽病菌Glomerella cingulata的抑制率在80%以上,2-异 NFDA1 唑取代的化合物 4a 对番茄早疫病菌 Alternaria solani 、苹果炭疽病菌和水稻稻瘟病菌 Magnaport hegrisease 的抑制率达100%。     

N-(芳基磺酰氨基乙基)-1,6-己内酰胺的合成及杀菌活性

以环己酮为原料,合成了9个结构新颖的N-(芳基磺酰氨基乙基)-1,6-己内酰胺( 3 ),其结构均经IR、1H NMR、13C NMR和元素分析确证。初步的生物活性测定结果表明,部分化合物对供试的6种病原真菌具有一定的杀菌活性,其中 3a、3b、3d和3g 对番茄叶霉病菌的抑制活性与对照药剂百菌清相当,抑制率大于90％。