Antifungal activity of halophenols and halonitrophenols

Summary Thirty one compounds (phenol; its 12 possible monohalo analogues; 18 nitrophenols (2- and 4-nitrophenols, 4-, 5-, and 6-halo-2-nitrophenols, 3-halo-4-nitrophenols)) were tested for antifungal activity against six fungi (A. niger, A. oryzae, M. verrucaria, T. viride, M. cirinelloides, andT. mentagrophytes) inSabouraud dextrose broth. The two most fungitoxic compounds of those studied were 5-fluoro- and 5-iodo-2-nitrophenols which inhibited all the fungi at concentrations under 10 µg/ml. 6-Iodo-2-nitrophenol inhibited five fungi at a concentration below 10 µg/ml andM. cirinelloides at 10–100 µg/ml.

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Fungizide Aktivität von Halogenphenolen und Nitrohalogenphenolen

Zusammenfassung 31 Verbindungen (Phenol; seine 12 möglichen monohalogenierten Derivate; 18 Nitrophenole (2- und 4-Nitrophenole, 4-, 5- und 6-Halogen-2-nitrophenole, 3-Halogen-4-nitrophenole)) wurden gegenüber 6 Pilzstämmen (A. niger, A. oryzae, M. verrucaria, T. viride, M. cirinelloides, T. mentagrophytes) inSabouraud-Nähmedium auf ihre fungizide Aktivität untersucht. Am effizientesten waren dabei 5-Fluor- und 5-lod-2-nitrophenole (Hemmung aller Stämme bei Konzentrationen <10 µg/ml). 6-lod-2-nitrophenol war gegen 5 Pilze bei Konzentrationen <10 µg/ml und gegenüberM. cirinelloides zwischen 10 und 100 µg/ml aktiv.

     

Design,synthesis, and bioactivity of nortopsentin analogues containing 1,2,4-triazole moieties

Plant diseases are serious and difficult to control. Novel and efficient pesticides are urgently needed. A series of nortopsentin analogues were designed, synthesized, and evaluated for their antiviral activities and fungicidal activities. Compound 3g with higher antiviral activity than nortopsentin D and ribavirin emerged as new antiviral lead compound. Further fungicidal activity tests revealed that nortopsentin analogues displayed broad-spectrum fungicidal activities. Compounds 3a , 3d , and 3f displayed higher antifungal activities against Cercospora arachidicola Hori than commercial fungicides carbendazim and chlorothalonil. Current research has laid a foundation for the application of nortopsentin analogues in plant protection.     

From Carbohydrates to Complex Organofluorines: Synthesis,Conformation, and Lipophilicity of Multivicinal-Fluorine-Containing Hexitol Analogues

There is growing interest in the preparation of fluorine-containing organic molecules. Multivicinal-fluorine analogues are among the most intriguing and promising compounds, but their physical and biological investigations are held back by challenging syntheses. Herein, we report on the synthesis of a large set of novel polyfluorohexitols. The dominant solution-state conformation of all trifluorohexitols was determined, and the solid-state conformations of some analogues were compared. Finally, the lipophilicity of a large set of polyfluorinated hexopyranose and hexitol analogues was attributed by using a log P determination method based on ¹⁹F NMR spectroscopy.     

Intramolecular synergism,an explanation for the enhanced fungitoxicity of halo-8-quinolinols

Summary An antifungal study againstAspergillus niger,A. oryzae,Myrothecium verrucaria, andTrichoderma viride in Yeast Nitrogen Base supplemented with 1%D-glucose and 0.088%L-asparagine was carried out using 8-quinolinol and 3-, 5-, 6-, 7-, 3,6-, and 5,7-chlorinated and brominated-8-quinolinols. Binary mixtures of 3- and 6-halo- and 5- and 7-halo-8-quinolinols were intermolecularly synergistic. MICs of the monohalo synergistic mixtures admixed with a MIC of the corresponding dihalo-8-quinolinols were not synergistic. The dihalo-8-quinolinols with substituents in positions corresponding to those of the synergistic binary mixtures appeared to attack the same sites of action as the binary pairs. The enhanced activities of 3,6- and 5,7-dichloro-8-quinolinols and 3,6- and 5,7-dibromo-8-quinolinols are believed to be due to intramolecular synergism. The greater fungitoxicity of 5-, 6-, and 7-monohalo-8-quinolinols over 8-quinolinol can also be explained as due to intramolecular synergism. 3,6-Dihalo- and 5,7-dihalo-8-quinolinols formed synergistic pairs of compounds.

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Intramolekularer Synergismus als Erklärung für die erhöhte Fungitoxizität von halogenierten 8-Chinolinolen

Zusammenfassung 8-Chinolinol und verschiedene halogenierte 8-Chinolinole wurden auf ihre Fungitoxizität gegenüberAspergillus niger,A. oryzae,Myrothecium verrucaria undTrichoderma viride untersucht. Binäre Mischungen von 3- und 6-Halogen- bzw. 5- und 7-Halogen-8-chinolinol zeigten intermolekularen Synergismus, während bei Mischungen von mono- und dihalogenierten 8-Chinolinolen kein entsprechender Effekt beobachtet werden konnte. Die erhöhte Aktivität von 3,6-und 5,7-Dichlor-8-chinolinol und 3,6- und 5,7-Dibrom-8-chinolinol wird durch intramolekularen Synergismus erklärt, desgleichen die höhere Aktivität monohalogenierter 8-Chinolinole gegenüber 8-Chinolinol. 3,6-Dihalogenierte und 5,7-dihalogenierte 8-Chinolinole bilden synergistische Paare.

     

Herbicidal Activity of Phosphonic,Phosphinic and Phosphinous Acid Analogues of Aromatic Amino Acids

Abstract

Over 40 phosphonic, phosphinic and phosphinous acid analogues of phenylglycine and phenylalanine were synthesized and screened for their herbicidal activity on Lepidium sativum (crest) and Cucumis sativus (cucumber). The most active appeared to be 2-amino-1-hydroxy-3-phenylpropylphosphonic acid which was equipotent with popular herbicide glyphosate. Also aminobenzylphosphonic acids, analogues of phenylglycine, exhibited notable herbicidal activity and thus represent a group of the most active herbicides found among simple aminophosphonic acids. Other compounds showed moderate herbicidal activity. Preliminary results indicate that analogues of aromatic amino acids display their activity as effectors of biosynthesis of aromatic amino acids.     

Microsynthesis and electron ionisation mass spectrometric analysis of chemical weapons convention (CWC)-related O,O-dialkyl-N,N-dialkylphosphoramidates

The paper describes microsynthesis and GC/EIMS analysis of O,O-dialkyl-N,N-dialkylphosphoramidates (DADAPs). DADAPs belong to schedule 2B6 category of chemical weapons convention (CWC), as they are important markers of the chemical warfare agent Tabun and its analogues. The study was undertaken to develop a spectral database of DADAPs for verification of CWC. The reported synthetic strategy can be adopted to prepare several analogues of DADAPs simultaneously and rapidly during official proficiency tests, for the unambiguous identification of analytes within a short period. Based on the EIMS data of more than 60 compounds, fragmentation routes are proposed which explain the formation of most of the characteristic fragment ions. Subtle differences in EIMS of isomeric DADAPs are discussed to facilitate their identification.     

cis‐Nitenpyram Analogues Containing 1,4‐Dihydropyridine: Synthesis,Insecticidal Activities,and Molecular Docking Studies

A novel series of cis‐nitenpyram analogues ( 2a – 2p ) were designed and prepared by introducing the 1,4‐dihydropyridine, with their cis‐configuration confirmed by X‐ray diffraction. Preliminary bioassays showed that most compounds exhibited good insecticidal activities at 20 mg/L against Aphis medicagini, and analogues 2a and 2d afforded the best activity, and both of them had 100% mortality at 4 mg/L. In addition, molecular docking studies were also performed to model the ligand‐receptor complexes, and the results explained the structure‐activity relationships observed in vitro, which may provide some useful information for future design of new insecticides.     

The synthesis of isoindolin-3-ones,Phthalazin-4(3H)-ones and related systems

The reaction between methyl 2-cyanobenzoate and its pyridine analogues gave isoindolin-3-ones, phthalazin-4(3H)-ones and their corresponding aza analogues. Some reactions of 1-benzylaminoiminoisoindolin-3-one 5b were investigated.     

Highly Stable,Amide‐Bridged Autoinducing Peptide Analogues that Strongly Inhibit the AgrC Quorum Sensing Receptor in Staphylococcus aureus

Blocking quorum sensing (QS) pathways has attracted considerable interest as an approach to suppress virulence in bacterial pathogens. Toward this goal, we recently developed analogues of a native autoinducing peptide (AIP‐III) signal that can inhibit AgrC‐type QS receptors and attenuate virulence phenotypes in Staphylococcus aureus. Application of these compounds is limited, however, as they contain hydrolytically unstable thioester linkages and have only low aqueous solubilities. Herein, we report amide‐linked AIP analogues with greatly enhanced hydrolytic stabilities and solubilities relative to our prior analogues, whilst maintaining strong potencies as AgrC receptor inhibitors in S. aureus. These compounds represent powerful tools for the study of QS.     

Highly Stable,Amide‐Bridged Autoinducing Peptide Analogues that Strongly Inhibit the AgrC Quorum Sensing Receptor in Staphylococcus aureus

Blocking quorum sensing (QS) pathways has attracted considerable interest as an approach to suppress virulence in bacterial pathogens. Toward this goal, we recently developed analogues of a native autoinducing peptide (AIP‐III) signal that can inhibit AgrC‐type QS receptors and attenuate virulence phenotypes in Staphylococcus aureus. Application of these compounds is limited, however, as they contain hydrolytically unstable thioester linkages and have only low aqueous solubilities. Herein, we report amide‐linked AIP analogues with greatly enhanced hydrolytic stabilities and solubilities relative to our prior analogues, whilst maintaining strong potencies as AgrC receptor inhibitors in S. aureus. These compounds represent powerful tools for the study of QS.     

Synthesis,Insecticidal Assay and Molecular Docking Study of Novel Neonicotinoids N‐Oxide Analogues

Eight novel neonicotinoids N‐oxide analogues were designed and synthesized. All the compounds have been identified by ¹H NMR and HRMS. The N‐oxide analogues exhibit high insecticidal activity against cowpea aphids (Aphis craccivora) at 250 mg·L^?1. The influence of N‐oxide formation on the biological activity was elucidated by computational chemical study, and it indicated that the water bridge hydrogen bonding network was broken due to the influence of the O atom connected with the pyridine ring.     

β‐Octamethoxy‐Substituted 22π and 26π Stretched Porphycenes: Synthesis,Characterization, Photodynamics,and Nonlinear Optical Studies

Three meso‐expanded tetrapyrrolic aromatic macrocycles, including 22π and 26π acetylene–cumulene bridged stretched octamethoxyporphycenes and octamethoxy[22]porphyrin‐(2.2.2.2), are reported, for the first time, by modification of previously reported synthetic methods. This strategy led to an enhancement in the overall yield of their corresponding octaethyl analogues. The methoxy‐substituted expanded porphycenes display slightly blueshifted absorption relative to their ethyl analogues, along with very weak fluorescence, probably due to efficient intramolecular charge transfer (ICT). Additionally, the two‐photon absorption (TPA) cross sections of these macrocycles were evaluated; these are strongly related to core expansion of the porphyrin aromaticity through increased meso‐bridging carbon atoms as well as conformational flexibility and substitution effects at the macrocyclic periphery. In particular, the octamethoxy stretched porphycenes display strong TPA compared with the octaethyl analogues due to the dominant ICT character of methoxy groups with a maximum TPA cross section of 830 GM at 1700 nm observed for 26π‐octamethoxyacetylene–cumuleneporphycene.     

Synthesis,stereochemistry, and opioid receptor binding activity of heterocyclic analogues of BW373U86

The synthesis of a series of heterocyclic analogues of (±)-4-((αR*)-α-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazmyl)-3-hydroxybenzyl)-N,N-diethylbenzarrude (BW373U86) for screening against opioid receptors is described. The intermediate α-heterocyclic benzyl alcohols 24 were synthesized either by low temperature reaction of lithioheterocycles with 3-((tert-butyldimethylsilyl)oxy)benzaldehyde ( 10 ) or by reaction of 3-((tert-butyldimethylsilyl)oxy)phenylmagnesium bromide ( 19 ) with heterocyclic carbaldehydes. The α-heterocyclic benzyl alcohols 24 were converted to chloromethines ( 25 ) with thionyl chloride and used to alkylate with trans-1-allyl-2,5-dimethylpiperazine ( 5 ) to give diastereomeric pairs of the target compounds. The bromoheterocycles were then derivatized to produce amides. Compounds that are potent and selective for the 5 or μ opioid receptors and some mixed δ/μ analogues are reported.     

Halovinylene Carbonates in Organic Synthesis. New synthetic methods (2)

Monohalo- and dihalovinylene carbonates constitute a new class of cyclophiles which permit simultaneous introduction of masked α-hydroxyketo and α-diketo functions, respectively, into the cycloadducts. Demasking can be performed by simple hydrolysis. Solvolytic opening of the carbonate ring leads to glycolic acid derivatives in the case of the monohalo compounds and to glyoxylic acid derivatives with the dihalo compounds. Preparation of the title compounds, their potential as synthetic reagents, and the chemistry of their simple reaction products are surveyed from a preparative viewpoint.     

Oligosaccharide Analogues of Polysaccharides,Part 22 , Synthesis of Cyclodextrin Analogues Containing a Buta‐1,3‐diyne‐1,4‐diyl or a Butane‐1,4‐diyl Unit

The peracetylated hexaamylose (maltohexaose) 18 was obtained by an improved acetolysis of cyclomaltohexaose (α‐cyclodextrin, α‐CD, 16 ), and transformed into the benzyl‐ and 4‐chlorobenzyl‐protected thioglycosides 22 and 23 , respectively (Scheme 2). Sequential chain elongation of 22 and 23 by glycosidation of the C‐ethynylated glucosides 9 and 11 gave the α‐anomeric heptaglycosides 24 and 26 , respectively, and their anomers 25 and 27 (Scheme 3). These were transformed into the glycosyl acceptors 28 , 30 , and 31 . Glycosidation of 28 and 30 by 13 and 15 , respectively, led to the benzyl‐protected octasaccharides 32 (αα₅α) and 33 (βα₅α), and to the chlorobenzylated analogues 34 (αα₅α) and 35 (βα₅α), while glycosidation of 31 led to the 4‐chlorobenzyl‐protected analogues 36 (αα₅β) and 37 (βα₅β) (Scheme 4). Hay coupling of O‐Bn‐ and O‐Ac‐protected linear octaoses 32 (αα₅α) and 33 (βα₅α) led to the cyclooctaamylose (γ‐cyclodextrin) analogues 38 and 43 , respectively (Scheme 5). Similarly, the 4‐chlorobenzyl‐protected analogues 34 and 35 gave 39 and 44 , and the anomeric linear precursors 36 and 37 provided the cyclootaamylose analogues 48 and 50 , respectively (Scheme 6). The influence of the constitution and configuration of the linear precursors on the rate and yield of the cyclisation was relatively weak. Deprotection and hydrogenation of 38 and 43 yielded the γ‐CD analogues 42 (αα₅α) and 47 (βα₅α), where one glycosidic O‐atom is replaced by a butanediyl group, while FeCl₃‐promoted dechlorobenzylation of 39 and 44 did not affect the butadiyne moiety and afforded the acetyleno γ‐CD's 40 (αα₅α) and 45 (βα₅α), respectively. Similarly, deprotection of 48 and 50 afforded the acetyleno γ‐CD analogues 49 (αα₅β) and 51 (βα₅β), respectively, which contain one butanediyl moiety instead of a glycosidic O‐atom. MM3* Force‐field calculations evidence the strong influence of the configuration and constitution of the new γ‐CD analogues on the shape of the cavity.     

The synthesis of some derivatives of 4,5,6,6a,7,12-hexahydroisoquinolino [8,l -ab]carbazole

As part of a general project on the chemistry of alkaloid analogues, the synthesis of derivatives 5 , of 4,5,6,6a,7,12-hexahydroisoquinolino[8,l-ab]carbazole, which can be considered as ring D indole analogues of the aporphine skeleton, was investigated. Compounds of this type are of interest on two grounds. Firstly it is conceivable some may occur naturally; and secondly, they may display unusual pharmacological properties, since the side-chain configuration of the tryptophan residue is intermediate between that present in lysergic acid diethylamide and the yohimbine-reserpine type alkaloids.     

Alkyl-, Aryl-, Vinyl-, and Heterosubstituted Organozirconium Compounds. -Selective nucleophiles of low basicity. Preliminary communication

Solutions of the title compounds are accessible from organolithium reagents and trialkoxyzirconium chloride (equation 2). In contrast to their titanium analogues, vinylzirconium reagents are stable enough to be employed. Generally, organozirconium reagents are highly selective aldehyde and ketone carbonylophiles of exceedingly low basicity (Tables 1, 2, 3 and typical procedure).     

Syntheses, structures and reactivities of designed analogues of cobalt(III)- bleomycinsz : Insight into the mechanism of sequence-specific DNA cleavage upon illumination

Three Co (III) complexes of a designed ligand PMAH that mimics the metal-binding domain of the antitumor antibioticbleomycin (BLM) have been isolated and structurally characterized. The coordination structures of the various forms of Co(III)-BLMs have been established on the basis of spectral similarities between these synthetic analogues and the corresponding Co(III)-BLMs. All three analogues, like Co(III)-BLMs, induce DNA strand scission upon UV illumination. Both DNA cleavage and spin trapping experiments demonstrate that UV irradiation of the analogues generates a C/N-based radical on the ligand framework which rapidly reacts with water to produce -OH radical near the DNA helix and causes strand scission. A similar mechanism could account for the photoactivity of the Co(III)-BLMs. Covalent attachment of DNA-binding groups to these analogues enhances the DNA-affinities and photocleavage efficiencies to a great extent. The hybrid analogues promote sequence-specific DNA photodamage at micromolar concentrations. The metallated cores of the hybrid analogues are the primary determinant of the observed sequence-specificity. Details of the mode of binding of the hybrid analogues to DNA have been explored by NMR techniques.     

Synthese von racemischen,isomeren Desoxo-4, 14-didemethyl-cassain-Derivaten. 4. Mitteilung über Cassain-Analoga

For the synthesis of demethyl analogues of Erythrophleum alkaloids, the tricyclic ketone 14 (trans-anti-trans) was prepared. The Horner reaction on 14 led to a mixture of cis/trans compounds, which could be separated into the homogeneous racemic isomers 21 and 22 . These compounds were transformed into the corresponding 2-dimethylamino-ethyl esters of their 3-dehydro and 3-O-carbamoyl derivatives.     

Synthesis and Biological Evaluation of New Dipyridylpteridines,Lumazines, and Related Analogues

Condensation of 4,5‐diaminopyrimidines 2 and 3 with 2,2ʹ‐dipyridil ( 4 ) afforded 6,7‐bis(2‐pyridyl)pteridine‐2‐one analogues 5 and 7 , respectively. Analogously, 6,7‐bis(2‐pyridyl)luamzine derivatives 13 , 15 , 17 , and 23 were synthesized from reaction of 5,6‐diamino‐2‐thiopyrimidines 13 , 14 , and 22 with 4 , respectively, while condensation of 4,5,6‐triaminopyrimidines ( 25 ) or 5,6‐diamino analogue 26 with 4 furnished the 4‐amino‐pteridine analogue 27 and 28 , respectively. Thiation of the new pteridines and lumazines afforded the 4‐thio analogues 6 , 8 , 16 , and 24 . Treatment of 6 and 8 with methanolic ammonia afforded the 4‐isopterine analogues 9 and 10 , respectively. Alkylation of 15 with substituted phenacyl chloride furnished 18 and 19 , which cyclized to the thiazolo‐pteridine derivatives 20 and 21 , respectively, on treatment with polyphosphoric acid. Alternatively, 27 was prepared from treatment of 24 with methanolic ammonia under drastic conditions. Condensation of 2 or 29 with 2‐oxo‐2‐(thiophen‐2‐yl)acetaldehyde oxime ( 11 ) gave the 6‐(2‐thienyl)‐pteridine‐4‐one ( 12 ) and 5‐chloro‐2‐(2‐thienyl)pyrido[3,4‐b ]pyrazine ( 31 ), respectively. All compounds were evaluated for their antiviral activity against the replication of HIV‐1 and HIV‐2 in MT‐4. Some of the synthesized compounds were tested against the bacterial species, Escherichia coli and Staphylococcus aureus , as well as fungal species, Candida tropicalis and Candida albicans .