Cyclopropane Carboxylate Research Articles

Cognitive and Histopathological Alterations in Rat Models of Early- and Late-Phase Memory Dysfunction: Effects of Sigma-1 Receptor Activation.

Sigma-1 receptors are highly expressed in brain areas related to cognitive function and are a promising target for anti-amnesic treatments. We previously showed that activation of sigma-1 receptors by the selective agonist compound methyl(1 R,2 S/1 S,2 R)-2-[4-hydroxy-4-phenylpiperidin-1-yl)methyl]-1-(4-methylphenyl) cyclopropane carboxylate [(±)-PPCC] promotes a remarkable recovery in rat models of memory loss associated to cholinergic dysfunction. In this study, we sought to assess the role of (±)-PPCC on working memory deficits caused by noradrenergic depletion. Animals with a mild or severe working memory deficits associated to varying degrees of noradrenergic neuronal depletion were treated with the sigma-1 agonist just prior to the beginning of each behavioral testing session. While (±)-PPCC alone at a dose of 1 mg/kg/day failed to affect working memory in lesioned animals, its association with the α2 adrenergic receptor agonist clonidine, completely blocked noradrenaline release, significantly improving rat performance. This effect, distinct from noradrenaline activity, is likely to result from a direct action of the (±)-PPCC compound onto sigma-1 receptors, as pre-treatment with the selective sigma-1 receptor antagonist BD-1047 reversed the improved working memory performance. Despite such clear functional effects, the treatment did not affect noradrenergic neuron survival or terminal fiber proliferation. Future studies are thus necessary to address the effects of long-lasting (±)-PPCC treatment, with or without clonidine, on cognitive abilities and Alzheimer's disease-like histopathology. Considering the already established involvement of sigma-1 receptors in endogenous cell plasticity mechanisms, their activation by selective agonist compounds holds promises as possibly positive contributor to disease-modifying events in neurodegenerative diseases.

N-Ylide Mediated Synthesis and Resolution of a Chiral Pyrimidinyl Cyclopropane Carboxylic Acid

N-Ylide Mediated Synthesis and Resolution of a Chiral Pyrimidinyl Cyclopropane Carboxylic Acid

Detection of L1014F knockdown resistance mutation in Culex tritaeniorhynchus populations

Culex tritaeniorhynchus is a major Japanese encephalitis virus vector distributed in Southeast Asia and surrounding countries. The aim of the present study is to investigate insecticide resistance status among 10 Cx. tritaeniorhynchus populations of the Mediterranean region of Turkey. Bioassay results indicated that all of the populations were resistant or at least possibly resistant to 1,1′-(2,2,2-Trichloroethane-1,1-diyl) bis (4-chlorobenzene) (DDT) (4%), [(dimethoxyphosphorothioyl) sulfanyl] butanedioate, Diethyl (malathion) (5%), and 2-[(Propan-2-yl) oxy] phenyl methylcarbamate (propoxur) (0,1%). Whereas, some of the populations were still susceptible to 3-Phenoxybenzyl (1RS)-cis, trans-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate (permethrin) (0,75%) and (S)-Cyano (3-phenoxy phenyl) methyl (1R,3R)-3-(2,2-dibromoethen-1-yl)-2,2-dimethylcyclopropane-1-carboxylate (deltamethrin) (0,05%). Biochemical analysis results showed altered alpha esterase, beta esterase, para-nitrophenyl acetate (PNPA), and glutathione-s-transferase (GST) levels in some populations while all of the populations had increased oxidase levels except for the Yumurtalık population. Additionally, all of the populations had sensitive acetylcholinesterase (AChE) levels similar to the control group except for the Erzin population. Correlation analysis showed a significant correlation between mortality rates for deltamethrin and alpha esterase, beta esterase, PNPA, and GST levels while mortality rates for permethrin were significantly correlated with GST levels. An allele-specific polymerase chain reaction (AS-PCR) detected high L1014F allele frequency in the populations. Overall results indicate the urgent need for monitoring and mapping of insecticide resistance in Cx. tritaeniorhynchus populations of the study area for effective vector control management.

Characterization of tars from recycling of PHA bioplastic and synthetic plastics using fast pyrolysis

The aim of this study was to investigate the pyrolysis products of polyhydroxyalkanoates (PHAs), polyethylene terephthalate (PET), carbon fiber reinforced composite (CFRC), and block co-polymers (PS-b-P2VP and PS-b-P4VP). The studied PHA samples were produced at temperatures of 15 and 50 oC (PHA15 and PHA50), and commercially obtained from GlasPort Bio (PHAc). Initially, PHA samples were analyzed by nuclear magnetic resonance (NMR) spectroscopy and size exclusion chromatography (SEC) to determine the molecular weight, and structure of the polymers. Thermal techniques such as thermogravimetry (TG) and differential scanning calorimetry (DSC) analyses were performed for PHA, CFRC, and block co-polymers to investigate the degradation temperature range and thermal stability of samples. Fast pyrolysis (500 oC, ∼102 °C s−1) experiments were conducted for all samples in a wire mesh reactor to investigate tar products and char yields. The tar compositions were investigated by gas chromatography–mass spectrometry (GC–MS), and statistical modeling was performed. The char yields of block co-polymers and PHA samples (<2 wt. %) were unequivocally less than that of the PET sample (~10.7 wt. %). All PHA compounds contained a large fraction of ethyl cyclopropane carboxylate (~ 38–58 %), whereas PAH15 and PHA50 additionally showed a large quantity of 2-butenoic acid (~8–12 %). The PHAc sample indicated the presence of considerably high amount of methyl ester (~15 %), butyl citrate (~12.9 %), and tributyl ester (~17 %). The compositional analyses of the liquid fraction of the PET and block co-polymers have shown carcinogenic and toxic properties. Pyrolysis removed matrices in the CRFC composites which is an indication of potential recovery of the original fibers.

​Potential of Lactic Acid Bacteria in Plant Growth Promotion

Background: Lactic acid bacteria are regarded the most important bacteria concerning food fermentation, pharmaceutical and special dietary applications. Strains have been isolated from environments rich in available carbohydrate substrates, such as food and feed, but also in human and animal cavities and in sewage and plant material. Besides lactic acid, other side products include acetate, ethanol, CO2, formate and succinate. The most important advantage of Lactic acid bacteria making them suitable for the use in food biotechnology, is that they are generally recognized as safe (GRAS). Studies on Lactic acid bacteria isolated from aerial parts of plants are scarce. Bacteria that colonize plant roots and promote plant growth are referred to as plant growth-promoting rhizobacteria. Several substances produced by antagonistic rhizobacteria have been related to pathogen control and indirect promotion of growth in many plants. The present work explores the potential use of Lactic acid bacteria in promotion of plant growth. Methods: Three isolates were obtained from aerial parts of pomegranate plant and confirmed by 16S rRNA sequencing to belong to Leuconostoc sp. The isolates were checked for plant growth promoting traits viz. antifungal activity, production of plant growth hormones, enzymes and 1-amino cyclopropane carboxylate deaminase activity. Result: As LAB showed plant growth promoting traits, they can be suitably used for plant growth promotion.

Protein termini relocation plus random mutation: A new strategy for finding key sites in esterase evolution

A pharmaceutically relevant esterase, RhEst1, could catalyze the hydrolysis of (R,S)-ethyl-2,2-dimethyl cyclopropane carboxylate [(R,S)-DmCpCe] with excellent enantioselectivity, producing (S)-(+)-2,2-dimethyl cyclopropane carboxylic acid [(S)-DmCpCa], which is a key chiral building block for the synthesis of Cilastatin. In our previous work, a mutant RhEst1-M2 was identified with 6.4-fold higher activity than the wild-type. Additionally, the termini of RhEst1 protein were altered by circular permutation (CP), resulting in a mutant CP-176 which still maintains the catalytic activity of esterase. In this work, to improve the catalytic properties of RhEst1, the mutant CP-176 was taken as the parent of directed evolution. Consequently, a new mutant designated as CP-M1 (=CP-176G282S) was identified, indicating 3.2-fold catalytic efficiency enhancement and nearly 7 ℃ improvement in melting temperature (Tm) as compared with CP-176. Furthermore, the beneficial mutation “G282S” of CP-M1 was reversely introduced into RhEst1-M2, generating the best mutant M3 (=RhEst1-M2G167S), with 1.8-fold catalytic efficiency improvement and nearly 10 ℃ improvement of Tm, as compared with RhEst1-M2. This is the first report that the circular permutation and random mutagenesis were combined to reshape a protein, affording distinctly improved activity and thermostability.

Cyclopropanation of active methylene compounds with β-alkoxycarbonyl vinylsulfonium salts

An efficient synthesis of β-alkoxycarbonyl vinylsulfonium salts had been developed. Their reaction with indene-1,3-diones and other active methylene compounds provided cyclopropane carboxylates in good yields. A tentative reaction mechanism was proposed.

Preparation of Optically Active cis-Cyclopropane Carboxylates: Cyclopropanation of α-Silyl Stryenes with Aryldiazoacetates and Desilylation of the Resulting Silyl Cyclopropanes.

Optically active cis-cyclopropane carboxylates are prepared via the Rh2(S-PTAD)4-catalyzed cyclopropanation of α-silyl styrenes with aryl diazoacetates followed by desilylation of the resulting silyl cyclopropane carboxylates. The conjugation of the aryl ring with C═C bond and π stacking are proposed for the stereoselectivity of cyclopropanation, and configuration inversion is observed with the desilylation process.

Deltamethrin degradation and effects on soil microbial activity

Deltamethrin [(S)-cyano-3-phenoxybenzyl-cis-(1R,3R)-2,2-dimethyl) cyclo–propane carboxylate),1] labelled at gem-dimethyl groups of the cyclopropane ring was applied on two Egyptian soils at a level of 10 mg/kg soil for a laboratory incubation experiment under aerobic and anaerobic conditions. A steady decrease of soil extractable14C-residues, accompanied by a corresponding increase of non- extractable bound 14C-residues was observed over a 90-day incubation period. The percentage of evolved 14CO2 increased with time under aerobic and anaerobic conditions in both soils. The effect of deltamethrin on soil microorganisms as well as the counter effect of microorganisms on the insecticide was also investigated. As the incubation period increased, the inhibitory effect of the insecticide on the microorganisms decreased and the evolution of carbon dioxide depended on the applied dose. The nature of soil methanol soluble residues was determined by chromatographic analysis which revealed the presence of the parent insecticide as the main product in addition to four metabolites: 3-(2′,2′-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid (II); 3-phenoxybenzaldehyde (III); 3-phenoxybenzoic acid (IV); 3-phenoxybenzyl alcohol (V).

Synthesis of (S)-7-Amino-5-azaspiro[2.4]heptane via Highly Enantioselective Hydrogenation of Protected Ethyl 1-(2-Aminoaceto)cyclopropanecarboxylates

Highly effective asymmetric hydrogenation of protected ethyl 1-(2-aminoaceto)cyclopropane carboxylates in the presence of [RuCl(benzene)(S)-SunPhos]Cl was realized, and high enantioselectivities (up to 98.7% ee) were obtained. This asymmetric hydrogenation provides a key intermediate for the enantioselective synthesis of (S)-7-amino-5-azaspiro[2.4]heptane moiety of quinolone antibacterial agents.

Organotin(IV) carboxylates of cyclopropane carboxylic acid and 3‐cyclohexylpropanoic acid: synthesis, characterization and biological activity. The crystal structure of bis(cyclopropanecarboxylato) tetramethyldistannoxane

AbstractA series of tri‐ and di‐organotin(IV) derivatives of the types R3SnL, R2SnL2 and [(R2SnL)2O]2 have been synthesized by the reaction of tri‐ and di‐organotin(IV) chloride(s) with sodium cyclopropane carboxylate and sodium 3‐cyclohexylpropanoate. Based on spectroscopic evidence (IR and NMR), all the triorganotin carboxylates were found to be penta‐coordinated in the solid state (except the tricyclohexyltin derivative, which was found to be four‐coordinated) and four‐coordinated in the solution state. Attempted reaction of Me2SnCl2 with sodium cyclopropane carboxylate in 1:2 stoichiometry afforded a bis(dicarboxylato tetraorganodistannoxane) complex, {[Me2Sn(cyclo‐CH2)2CHCOO]2O}2. The X‐ray diffraction of this ‘dimethyltin(IV) complex’ shows that the compound possesses a tetranuclear aggregate with one bridging bidentate and other free organic ester type monodentate carboxylate groups in which each Sn atom has a five‐coordinated geometry. These complexes were also screened for their antifungal activities. Copyright © 2008 John Wiley &amp; Sons, Ltd.

Investigating the Mechanistic Basis for Hepatic Toxicity Induced by an Experimental Chemokine Receptor 5 (CCR5) Antagonist Using a Compendium of Gene Expression Profiles

A compendium of hepatic gene expression signatures was used to identify a mechanistic basis for the hepatic toxicity of an experimental CCR5 antagonist (MrkA). Development of MrkA, a potential HIV therapeutic, was discontinued due to hepatotoxicity in preclinical studies. Rats were treated with MrkA at 3 dose levels (50, 250, and 500 mg/kg) for 1, 3, or 7 days. Hepatic toxicity (vacuolation, consistent with steatosis, and elevated serum transaminase levels) was observed at 250 and 500 mg/kg, but not at 50 mg/kg. Hepatic gene expression profiles were compared to a compendium of hepatic expression profiles. MrkA was similar to 3 beta-oxidation inhibitors (valproate, cyclopropane carboxylate, pivalate), 8 PPARalpha agonists (fenofibrate, bezafibrate and 6 fibrate analogues), and 3 other diverse compounds (diethylnitrosamine, microcystin LR & actinomycin D). These data indicate MrkA to be a mitochondrial inhibitor, and activation of PPARalpha-regulated transcription was thought to be due to an accumulation of endogenous ligands. While mitochondrial inhibition was likely responsible for steatosis, canonical pathway analysis revealed that progression to liver injury may be mediated by activation of the innate immune system primarily through NF-kB pathways. These results demonstrate the utility of a gene expression response compendium in developing transcriptional biomarkers and identifying the mechanistic basis for toxicity.

Effects of cypermethrin on rainbow trout (Oncorhynchus mykiss)

The aim of this study was to assess the effect of cypermethrin [(R,S)-&amp;alpha;-cyano-3-phenoxybenzyl (1RS)-cis,tra-3-(2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate] on rainbow trout (Oncorhynchus mykiss). The effect was assessed on the basis of the results of acute toxicity tests and on the comparison of results of haematological, biochemical and histopathological tissue examinations of a control and experimental group exposed to Alimetrine 10 EM pesticide preparation (active substance 100 g/l of cypermethrin). The acute semistatical toxicity test lasting 96 h was performed on rainbow trout juveniles. The 96hLC50 value of Alimethrine 10 EM was 31.4&amp;nbsp;&amp;micro;g/l. Examination of erythrocyte, leukocyte and biochemical profile and histopathological tissue examination was performed on 15 control and 15 experimental specimens of one-to-two-year-old rainbow trout after 96 h of exposure to Alimetrine 10 EM in the concentration of 31.4 &amp;micro;g/l. The experimental group showed significantly higher values (P &amp;lt; 0.01) of plasma ammonia (NH&lt;sub&gt;3&lt;/sub&gt;), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), lactate (LACT) and significantly lower (P &amp;lt; 0.01) values of alkaline phosphatase (ALP) compared to the control group. Also, a significant decrease in count of developmental forms of myeloid sequence, and segmented neutrophile granulocytes in the experimental group were found. Teleangioectasiae of secondary gill lamellae and degeneration of hepatocytes were observed with histopathological examination. No histopathological changes were demonstrated in tissues (skin, spleen, cranial and caudal kidney) of rainbow trout following exposure to cypermethrine. The cypermethrine-based Alimethrinee 10 EM pesticide preparation was classified among substances strongly toxic for fish.

Phototransformation of Alphacypermethrin as Thin Film on Glass and Soil Surface*

Photodegradation of alphacypermethrin ((RS)-α cyano-3-phenoxy benzyl (1RS) cis-3-(2,2,dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate) was studied as a thin film on glass surface and on black and red soil surfaces. A number of photoproducts from glass surfaces have been isolated, characterized and identified by gas chromatography-mass spectroscopy (GC-MS). However, only two of them viz. 3-phenoxy benzyl alcohol and [2,2-dichlorovinyl-3(2,2,dimethyl) cyclopropane carboxylate] could be identified from both the soil. Rate of photodegradation on glass and soil surface under UV and sunlight followed first order kinetics with significant correlation coefficients. The rate of photodegradation was greater on black than on red soil. *A part of Ph.D. thesis of the first author in the Department of Chemistry submitted to the Bundelkhand University, Jhansi, U.P., India.

α‐Lithiated Aryloxiranes: Useful Reactive Intermediates

AbstractFor Abstract see ChemInform Abstract in Full Text.

α-Lithiated Aryloxiranes: Useful Reactive Intermediates

This account focuses on the generation of α-lithiated aryloxiranes such as lithiated oxazolinylaryloxiranes, lithiated styrene-, phenylpropylene- and stilbene oxides, their chemical and configurational stability, reactivity and some synthetic applications. It is shown how these special reagents have been successfully employed for the preparation of a variety of substances including polysubstituted aryloxiranes, highly strained heterocyclic compounds, α,β-epoxy-y-butyrolactones, cyclopropane carboxylates.

Synthetic Approach to Substituted Cyclopropanes Based on the Coupling Reaction of Lithiated Chloroalkyloxazolines with Fischer Carbene Complexes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthetic approach to substituted cyclopropanes based on the coupling reaction of lithiated chloroalkyloxazolines with Fischer carbene complexes.

Regioselective addition of lithiated oxazoline 2a, easily available from 2-(1-chloroethyl)-4,4-dimethyl-2-oxazoline 1a (LDA, THF, -98 degrees C), to alpha,beta-unsaturated Fischer carbene complexes 3 afforded cyclopropylcarbene complexes 4 as sole diastereoisomers. Exposure of carbene complexes 4a-c (M = Cr) to air and sunlight gave cyclopropane carboxylate derivatives 5a-c. A plausible mechanistic explanation is proposed. Moreover, when lithiated oxazoline 2b was generated from 1b in the presence of the carbene complex 3a,b, the oxazolinylcyclopropane carboxylates 6a,b formed as a 1:1 mixture of diastereoisomers. Chiral lithiated oxazoline 2c added regioselectively and diastereoselectively to chromium complexes 3a,b and to tungsten complexes 3d,e, leading, after oxidation of the metal fragment, to esters 7a,b with good diastereoselectivity (dr = 4:1). The reaction of lithiated oxazoline 2d with chromium complex 3b and tungsten complex 3e proceeded less diastereoselectively, furnishing, in both cases, after oxidation, the ester 7c as a 3:2 diastereoselective mixture.

Biodegradation of β-Cyfluthrin by Fungi

Five fungal species, namely, Trichoderma viride strain 5-2, T. viride strain 2211, Aspergillus niger, A. terricola, and Phanerochaete chrysoporium were screened for degradation study of beta-cyfluthrin. Each fungal species was allowed to grow in Czapek dox medium containing beta-cyfluthrin (5 mg/mL) as the major carbon source of the medium. The highest degradation of beta-cyfluthrin was observed by T. viride 5-2 (T(1/2) = 7.07 days), followed by T.viride 2211 (T(1/2) = 10.66 days). The degradation of beta-cyfluthrin followed first-order kinetics with a fast degradation rate during first 7 days of growth of the fungi. In the case of T. viride strain 5-2, five degradation products were isolated after 20 days of growth of the fungi, out of which three products were identified as alpha-cyano-4-fluorobenzyl-3- (2,2-dichlorovinyl)-2,2-dimethyl cyclopropane carboxylate, alpha-cyano-4-fluoro-3-phenoxy benzyl alcohol, and 3(2,2-dichlorovinyl)-2,2-dimethyl cyclopropanoic acid.

Modular ligands in asymmetric synthesis. Copper-mediated cyclopropanation

The chiral imidazoline/copper catalyst system efficiently mediates asymmetric intermolecular cyclopropanations. Complexes derived from ( R, R)- or ( S, S)-1,1-diphenylethylenediamine, cyclic ketones, and Cu(I) or Cu(II) triflates were compared. The reaction between (−)-menthyl diazoacetate and 1,1-diphenylethylene affords cyclopropane carboxylates in up to 80% yield and with up to 78% de.