The fungicidal activity of substituted 1, 4-naphthoquinones. Part 1: Alkylthio and arylthio derivatives

Some symmetrical and unsymmetrical 2, 3-bis(arylthio)-1, 4-naphthoquinones have been synthesised and assayed against Botrytis cinerea, Cladosporium fulvum and Venturia inaequalis. With the surprising exception of the 2, 3-bis(4-chlorophenylthio) derivative, the compounds were essentially inactive. The 2-phenylthio and lower 2-alkylthio derivatives showed a high level of activity, which was absent in the 2-pentylthio and higher homologues.     

The fungicidal activity of substituted 1, 4-naphthoquinones. Part II: Alkoxy,phenoxy and acyloxy derivatives

A representative group of 1, 4-naphthoquinone derivatives, bearing alkoxy, phenoxy and acyloxy substitutents in the 2-position, has been synthesised and assayed against Botrytis cinerea, Cladosporium fulvum and Venturia inaequalis. The alkoxy compounds exhibited moderate activity, which was enhanced by the presence of a 3-chloro and, to a lesser extent, a 3-bromo substituent. 2-Chloro-3-phenoxy derivatives were highly active, but diphenoxy compounds were inactive. Acyloxy derivatives possessed only weak activity unless a halogen atom was present in the 3-position; benzoyloxy compounds, however, were generally poor fungicides.     

Fungicidal activity and chemical constitution. XX. The activity of substituted 1,4-naphthohydroquinone esters and substituted 1,4-naphthoquinones against powdery mildews

Eleven 2-n-alkyl-, ten 2-n-alkyl-3-hydroxy- and ten 2-n-alkyl-2,3-epoxy-3-hydro-1,4-naphthoquinones, together with eighteen 1,4-naphthohydroquinone esters were tested as protectant fungicides against the apple and cucumber powdery mildews (caused by Podosphaera leucotricha and Sphaerotheca fuliginea respectively). In.general the former pathogen was more susceptible to compounds from all four series, the lowest 10⁵ED⁵⁰(M) being 0.7 for 2-n-octyl-2,3-epoxy-3-hydro-1,4 naphthoquinone.     

Fungicidal activity and chemical constitution. Part XXI: The activity of substituted 1, 4-naphthoquinones and quinoline-5, 8-diones against apple powdery mildew

Several series of alkyl-substituted amino-, bromo-, chloro-, fluoro- and hydroxy-1, 4-naphthoquinones, as well as some 6-alkylaminoquinoline-5, 8-diones and 7-alkyl-6-hydroxyquinoline-5, 8-diones were prepared and tested as protectant fungicides against apple powdery mildew (caused by Podosphaera leucotricha). While most of the compounds did not reduce infection when applied at 10^?3M, several 3-alkyl-2-bromo-and 3-alkyl-2-chloro-1, naphthoquinones were found to have ED₅₀ values below 50 × 10^?5M.     

取代苯甲酸酯类化合物的合成与杀菌活性

以取代苯甲酸和异戊醇为原料,合成了14个未见文献报道的取代苯甲酸酯类化合物,其结构均通过红外光谱、核磁共振氢谱和气相色谱-质谱联用（GC-MS）确证。生物活性测定结果表明:14个新化合物对灰霉病菌Botrytis cinerea、稻瘟病菌Piricularia oryzae和纹枯病菌Rhizoctonia solani的活体杀菌活性均好于离体杀菌活性,尤其是化合物3j在500 μg/mL下对黄瓜灰霉病的活体防效达96.4%,3e（500 μg/mL）对水稻稻瘟病的活体防效为96.3%。     

Insecticidal and fungicidal activity of new synthesized chitosan derivatives

Chitosan, the N-deacetylated derivative of chitin, is a potential biopolysaccharide owing to its specific structure and properties. In this paper, we report on the synthesis of 24 new chitosan derivatives, N-alkyl chitosans (NAC) and N-benzyl chitosans (NBC), that are soluble in dilute aqueous acetic acid. The different derivatives were synthesized by reductive amination and analyzed by 1H NMR spectroscopy. A high degree of substitution (DS) was obtained with N-(butyl)chitosan (DS 0.36) at a 1:1 mole ratio for NAC derivatives and N-(2,4-dichlorobenzyl)chitosan (DS 0.52) for NBC derivatives. Their insecticidal and fungicidal activities were tested against larvae of the cotton leafworm Spodoptera littoralis (Boisduval) (Lepidoptera: Noctuidae), the grey mould Botrytis cinerea Pers (Leotiales: Sclerotiniaceae) and the rice leaf blast Pyricularia grisea Cavara (Teleomorph: Magnaporthe grisea (Hebert) Barr). The oral feeding bioassay indicated that all the derivatives had significant insecticidal activity at 5 g kg(-1) in artificial diet. The most active was N-(2-chloro-6-fluorobenzyl)chitosan, which caused 100% mortality at 0.625 g kg(-1), with an estimated LC50 of 0.32 g kg(-1). Treated larvae ceased feeding after 2-3 days; the mechanism of action remains unknown. In a radial hyphal growth bioassay with both plant pathogens, all derivatives showed a higher fungicidal action than chitosan. N-Dodecylchitosan, N-(p-isopropylbenzyl)chitosan and N-(2,6-dichlorobenzyl)chitosan were the most active against B cinerea, with EC50 values of 0.57, 0.57 and 0.52 g litre(-1), respectively. Against P grisea, N-(m-nitrobenzyl)chitosan was the most active, with 77% inhibition at 5 g litre(-1). The effect of different substitutions is discussed in relation to insecticidal and fungicidal activity.     

含三唑结构的环己甲酰胺衍生物的合成及杀菌活性

为寻找高效的杀菌活性化合物,在前期十三元氮杂大环内酯化合物   Z13-5  的基础上尝试进行结构改造,保留三唑与环己甲酰胺结构,通过酰胺化及叠氮-炔烃点击反应等设计并合成了26个未见文献报道的目标化合物,其结构均通过核磁共振氢谱 (1H NMR)、碳谱 (13C NMR) 及高分辨质谱 (HRMS) 确证。初步杀菌活性测定结果表明:与化合物   Z13-5  相比,目标化合物的杀菌活性有所下降,在50 mg/L下,除化合物   7g  对辣椒疫霉病菌的抑制率可达91%外,其余化合物对供试病原真菌的抑制率均低于50%。     

The synthesis and fungicidal activity of derivatives of o- and p-Cyclohexylphenyl phosphorodichloridates and dichloridophosphorothioates

The synthesis of o- and p-cyclohexyphenyl phosphorodichloridates and dichloridophosphorothioates and their conversion into the corresponding dimethyl phosphates, phosphorodihydrazides, and phosphorodihydrazones, is discussed. o- and p-Cyclohexylphenyl N-phenylphosphoramidic chlorides were converted to the hydrazide and the O-methyl ester. The phosphorodichloridates were converted to the dihydrogen phosphates, but the dichloridophosphorothioates could not be hydrolysed in an analogous manner. Structure-activity relationships have been briefly discussed; the most active compound was o-cyclohexylphenyl O-methyl phosphoroisopropylidene hydrazone.     

Insecticidal 2-hydroxy-3-alkyl-1,4-naphthoquinones: correlation of inhibition of ubiquinol cytochrome c oxidoreductase (complex III) with insecticidal activity

The insecticidal and in vitro activities of four homologous series of 2-hydroxy and acetoxy-3-substituted-1,4-naphthoquinones have been measured and correlated with their (Log) octanol/water partition coefficients (Log Ko/w). In vitro activity against mitochondrial complex III was only exhibited by 2-hydroxy-3-alkyl-1,4-naphthoquinones, indicating that the 2-acetoxy compounds act as proinsecticides. Good correlation was observed between in vivo activity against the two-spotted spider mite, Tetranychus urticae and inhibition of complex III isolated from blowfly flight muscle. Both hydroxy and acetoxy analogues of individual compounds exhibited similar levels of in vivo activity with optimum activity for analogues with Log Ko/w values of 7-8. In contrast, the acetoxy derivatives showed superior in vivo activity against the tobacco whitefly, Bemisia tabaci. Complex III isolated from whitefly was optimally inhibited by hydroxy analogues with lower Log Ko/w values (6.0-6.5) and was also more sensitive than the blowfly enzyme to all the compounds tested.     

5-亚环己基-咪唑-2,4-二酮及其衍生物的合成及杀菌活性

以环己酮及其衍生物和2-硫代-咪唑-2,4-二酮及咪唑-2,4-二酮膦酸酯为起始原料,经Knoevenagel 缩合反应和Wittig-Horner反应合成了10个5-亚环己基-咪唑-2,4-二酮系列衍生物,其中7个为新化合物,其化学结构经1H NMR、IR和MS确证。初步生物活性测定结果表明:在50 μg/mL 下,部分目标化合物对油菜菌核病菌 Sclerotinia scleotiorum 显现出良好的抑制活性,其中 7I和7J 的EC50分别为8.06 和8.48 μg/mL。     

Bactericidal and fungicidal activity of Aspergillus ochraceus metabolites and some derivatives

The bactericidal and fungicidal activities of aspyrone and asperlactone, secondary metabolites of Aspergillus ochraceus, and some aspyrone derivatives were studied. In general, aspyrone exhibited better activity than asperlactone or aspyrone derivatives. The inhibition patterns of the assayed compounds were different. Helminthosporium monoceras was the tested mould most inhibited by the studied compounds. The comparative study of the activity of the different compounds showed that the epoxy group seems to be necessary for activity against some micro-organisms. © 1998 SCI     

吩嗪-1-羧酸双酰肼衍生物的合成、杀菌活性及韧皮部的输导性研究

天然产物吩嗪-1-羧酸（PCA,申嗪霉素）及其衍生物吩嗪-1-甲酰肼具有独特的化学结构和优良的杀菌等生物活性,但均没有韧皮部输导性。本文以具有抑菌活性的吩嗪-1-羧酸和具有韧皮部输导性的马来酰肼为先导化合物,将马来酰肼中的双酰肼结构引入到吩嗪-1-羧酸中,设计、合成了17个新化合物,其结构均经过核磁共振氢谱、高分辨质谱及X-射线单晶衍射分析确证。初步生物活性测试表明:大部分目标化合物在50 mg/L下对水稻纹枯病菌Thanatephorus cucumeris表现出中等偏上的抑制活性,其中化合物6m的抑制率达92%。但输导性研究结果显示,目标化合物没有明显的韧皮部输导性。     

含哌啶噻唑结构的乙酰氨基衍生物的合成及杀菌活性

为了寻找高效的杀菌活性物质,以哌啶噻唑结构为母体,甘氨酸为连接基团,通过重氮化、氯化、成环和缩合等步骤合成了14个含哌啶噻唑结构的乙酰氨基衍生物,通过核磁共振氢谱 (1H NMR)、碳谱(13C NMR)及高分辨质谱 (HRMS)对化合物的结构进行确证。初步杀菌活性测定结果表明:甘氨酸作为连接基团对化合物杀菌活性的提高具有积极影响,其中,化合物 7a 、 7c 和 7g 在25 mg/L剂量下对黄瓜灰霉病菌的抑制率为68.7%、71.6%和67.2%,化合物 7a 、 7g 和 7i 对马铃薯晚疫病菌的抑制率分别为50.8%、61.9% 和55.8%。     

含苯并咪唑环的1,3,4-噻二唑酰胺衍生物的合成与抑菌活性

为寻找新型活性杂环化合物,通过活性亚结构拼接,以取代苯酚和氯乙酸为起始原料,经醚化、缩合、烃基化和氨解反应,设计并采用微波辅助合成了6种未见文献报道的含苯并咪唑环的1,3,4-噻二唑酰胺衍生物,其结构经红外和核磁共振氢谱确证。初步抑菌活性测试结果表明,所有目标化合物对5种供试病原菌都表现出一定的抑菌活性,其中,化合物7c、7d、7e和7f在50 mg/L下对5种供试病原菌的抑制率均达到80%以上。     

Synthesis and fungicidal activity of 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles

A series of eleven 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles was prepared by reaction of 2,3-dichloroquinoxalines with disodium (2)-2,3-dimercapto-2-butenedinitrile in N,N-dimethylformamide. These products were tested for in-vitro fungicidal activity by a Minimum Inhibitory Concentration (MIC) method. Several of these compounds showed broad-spectrum fungicidal activity. The activity exhibited by these compounds was greatly dependent upon the substituents of the quinoxaline ring, with the nitro-substituted derivatives showing the highest levels of antifungal activity. None of the compounds prepared, however, showed fungicidal activity comparable to that of the commercial fungicides screened.     

Fungicidal activity of 2-(1-alkenyl)-3-hydroxy-1,4-naphthoquinones and related compounds

The fungicidal activity of a series of 2-(1-alkenyl)-3-hydroxy-1,4-naphthoquinones and their acetates has been assessed against various fungi in vitro and against others, notably powdery mildews, in vivo, and the activity compared with that of analogous compounds bearing saturated side chains. Several of the compounds demonstrated a broad spectrum of activity in vitro. Whereas the presence of α-unsaturation in the side chain is essential for the in-vitro activity against the non-obligate fungi tested, it is of virtually no importance for the curative effect against Erysiphe graminis on barley. Only the corresponding acetates had activity against the latter pathogen.     

Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 1: pyrido[2,3‐b]pyrazines

BACKGROUND: The excellent fungicidal activity of [1,2,4]triazolo[1,5‐a]pyrimidines suggested the search for further analogues with improved properties. RESULTS: A series of novel trisubstituted pyrido[2,3‐b]pyrazines has been designed and prepared as 6,6‐biheterocyclic analogues of related 5,6‐bicyclic [1,2,4]triazolo[1,5‐a]pyrimidines. Their fungicidal activity was evaluated against the plant pathogens Puccinia recondita Rob. ex Desm. f. sp. tritici (Eriks.) CO Johnston (wheat brown rust), Mycosphaerella graminicola (Fuckel) Schroter (Septoria tritici Rob., leaf spot of wheat) and Magnaporthe grisea (Hebert) Barr (Pyricularia oryzae Cav., rice blast). Structure–activity relationship studies revealed the advantage of a fluoro substituent in position 6 and of a secondary amine in position 8. CONCLUSION: 8‐Amino‐7‐aryl‐6‐halogen‐substituted pyrido[2,3‐b]pyrazines have been prepared as 6,6‐biheterocyclic analogues of similarly substituted triazolopyrimidine fungicides. A concise four‐step synthesis route has been worked out to prepare these novel compounds from commercially available starting materials. [(R)‐(1,2‐Dimethylpropyl)]‐[6‐fluoro‐7‐(2,4,6‐trifluorophenyl)pyrido[2,3‐b]pyrazin‐8‐yl]amine showed excellent activity against three economically important phytopathogens. Copyright © 2009 Society of Chemical Industry     

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。     

Synthesis and fungicidal activity of N-2-(3-methoxy-4-propargyloxy)phenethyl amides. Part II: anti-oomycetic mandelamides

Novel types of anti-oomycetic compounds have been designed and prepared. The synthetic approach to these mandelamides is outlined. Biological data demonstrate their high efficacy against important plant diseases such as tomato and potato late blight (Phytophthora infestans De Bary) and grape downy mildew (Plasmopara viticola Berliner & de Toni). Structure-activity relationship studies are discussed. The new development product mandipropamid is presented.     

(4-亚甲基-5-羰基-3-四氢呋喃基)-苯甲酸甲酯衍生物的合成及其杀菌活性

为了探索天然产物Cedarmycins衍生物的结构与活性关系,以α-亚甲基-β-羟甲基-γ-丁内酯为起始原料,经过与不同取代的羧酸缩合,合成了19个新的(4-亚甲基-5-羰基-3-四氢呋喃基)-苯甲酸甲酯衍生物。杀菌活性测定结果表明,该类衍生物具有广谱的杀菌活性,尤其对水稻纹枯病菌Rhizoctonia solani和辣椒疫霉Phytophthora capsici显示出很强的杀菌活性,其中化合物2e(R=2,4-2Cl)对这2种病菌的EC50值约为1.6 mg/L。