Cyclopropane Carboxylate Research Articles

Synthesis of enantiopure monofluorinated phenylcyclopropanes by lipase-catalyzed kinetic resolution

All four stereoisomers of (2-fluoro-2-phenlycyclopropyl)methanol were synthesized using Amano PS lipase-catalyzed acylation and transesterification as key steps. Copper(I)-catalyzed cyclopropanation of α-fluoro styrene with ethyl diazoacetate and chromatographic separation gave diastereomerically pure cyclopropane carboxylates, which were then reduced with LiAlH 4. Whereas the enzymatic acylation gave low selectivities for trans-configured alcohols ( E=13) using different acyl donors, the corresponding cis-diastereomers were obtained with high enantiomeric excesses ( E >200). Additionally, kinetic resolution of different racemic esters of (2-fluoro-2-phenlycyclopropyl)methanol was achieved by lipase-catalyzed transesterification employing Amano PS in the presence of ethanol and the selectivities from this process were found to be comparable to those observed in the enzymatic acylation. The absolute configurations of the enantiomers were confirmed by X-ray structural analysis of the corresponding enantiopure p-bromophenyl carbamates. In addition, the stereochemistry of the product from the asymmetric cyclopropanation of α-fluoro styrene with a chiral bis(oxazoline) copper(I) catalyst was similarly determined.

ON THE SYNTHESIS OF (±) ETHYL 2,2-BIS(DIETHOXYPHOSPHORYL)-CYCLOPROPANE CARBOXYLATES

ABSTRACT The synthesis of (±) ethyl 2,2-bis(diethoxyphosphoryl)cyclopropane carboxylates 1 is described. The key-steps are a Michael-type addition and ensuing intramolecular cyclisation reaction.

ChemInform Abstract: Asymmetric Cyclopropanation of Vinyl Fluorides: Access to Enantiopure Monofluorinated Cyclopropane Carboxylates

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric Cyclopropanation of Vinyl Fluorides: Access to Enantiopure Monofluorinated Cyclopropane Carboxylates

The transition metal catalyzed cyclopropanation with alkyl diazoacetates of aliphatic or aromatic vinyl fluorides, prepared from the corresponding alkenes by bromofluorination and subsequent dehydrobromination, provides a smooth access to racemic 1 : 1 mixtures of cis/trans isomeric monofluorinated cyclopropane carboxylates. The application of enantiopure bis(oxazoline) ligands and copper(I) triflate makes the reaction trans-diastereoselective and enantioselective. For example, treatment of α-fluorostyrene (3a) with tert-butyl diazoacetate in the presence of 2 mol% of the catalyst prepared from (S)-tert-leucine-based 11b and CuOTf gave a 4 : 1 mixture of trans-2-fluoro-2-phenylcyclopropanecarboxylate (4e) with 93% ee and the corresponding cis-isomer 5e with 89% ee. The absolute configuration of the trans-isomer 4e has been determined to be (1S,2S) by X-ray structure analysis of a derivative.

Analysis of structure activity relationships for LPS-mimetic activities of taxane analogs in murine macrophages

The anti-tumor agent, paclitaxel (active ingredient of Taxol®), is best recognized for its ability to bind to microtubules and to block cell division. However, it has more recently been demonstrated to mimic the varied effects of bacterial lipopolysaccharide (LPS) in murine macrophages, actions that appear to be dissociable from its well-characterized β-tubulin binding capacity. Secretion of tumor necrosis factor alpha (TNFα) and induction of TNFα gene expression were assessed in macrophages treated with paclitaxel analogs. Two structural modifications resulted in elevated TNFα mRNA and protein secretion: (i) the presence of a cyclopropane carboxylate ester at C-4 rather than an acetate; or (ii) deoxygenation of the C-7 position. Certain modifications essentially eliminated activity: derivatization of the side chain 2′ hydroxy group to form an ethyl carbonate, the presence of a benzoate at C-4 rather than an acetate, or de-acetylization to leave a free hydroxy group at the C-10 position. Substitution of the phenyl group at the 3′ carbon position of the side chain with a 2-furyl group or the presence of a 2- or 3-pyridine carboxylate moiety at C-2 rather than a benzoate also resulted in a significant reduction in TNFα. These structure—activity relationships can be distinguished from those that affect the cytotoxic effects of paclitaxel which are attributable to its microtubule binding activity.

ChemInform Abstract: Diastereoselectivity in the Formation of Bicyclic Cyclopropane Carboxylic Acid Lactones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enzymatic resolution of (±)- cis-3-(2,2-dichloro-3,3,3-trifluoropropyl)-2,2-dimethylcyclopropane carboxylate

A novel biocatalytic kinetic resolution of a chemically labile racemic cis-3-(2,2-dichloro-3,3,3-trifluoropropyl)-2,2-dimethyl cyclopropane carboxylate ester is studied.

Synthesis of chiral bis(oxazolinyl)biferrocene ligands and their application to Cu(I)-catalyzed asymmetric cyclopropanation

Homochiral bis(oxazolinyl)biferrocene ligands, which have both planar and central chirality, are synthesized from oxazolinylferrocenes through a diastereoselective directed lithiation followed by an oxidative dimerization. Asymmetric cyclopropanation of styrene with diazoacetates in the presence of 5 mol% CuOTf-bis(oxazolinyl)biferrocene complexes gives 2-(phenyl)cyclopropane carboxylates in up to 99% ee.

Cytogenetic Effect of Supermethrin in Pig and Cattle Peripheral Lymphocytes

Dianovsky 1., K. Si vikova: Cytogenetic Effect of Supennethrin in Pig and Cattle Lymphocytes. Acta vet. Brno, 1997, 66:33-38. The synthetic pyrethroid insecticide supermethrin (RS)-alpha-cyano-3-phenoxybenzyl-(lRS)­ cis-3 (2,2-dichlorvinyl)-2,2-dimethyl cyclopropane carboxylate, was tested for its clastogenic ability in in vitro assays. Cultured pig and cattle peripheral lymphocytes were used for in vitro clastogenicity evaluation in the absence of S-9 mix. The final concentrations were 6 x 10-6M. 6 x to-SM and 6 x 10-4M. No significant differences were detectable in supermethrin's clastogenic potency at concentrations of 6 x to-6M and 6 x to-5M. respectively, in cattle. The highest concentration was positive (P < 0.05) and a decrease of mitotic index (MI) was also observed. The pig peripheral lymphocytes showed clastogenic effect (P < 0.05) at concentrations 6 x 10-5 M and 6 x 10-4 M. Cytotoxic effect expressed by MI value was also more perspicuous. Supermethrin was investigated for the induction of sister chromatide exchanges (SCE) in pig and cattle peripheral lymphocytes, but inadequate results of genotoxic potency not corresponding to the concentrations were found. The tested pyrethroid was characterized as more toxic than clastogenic or genotoxic. Pyrethroids, genotoxicity. in vitro. pig and cattle lymphocytes Supermethrin, a synthetic derivative of natural pyrethrin insecticides, belongs to the group of so-called pyrethroids. Supermethrin is a type II pyrethroid of Czech origin (Spolana, Neratovice) and similar in structure to cypermethrin. Chemically it is (RS)-alpha-cyano-3phenoxybenzyl-( IRS)-cis-3(2,2-dichlorvinyl)- 2,2-dimethyl cyclopropane carboxylate

Evaluation of the genetic toxicity of synthetic chemicals (II), a pyrethroid insecticide, fenpropathrin

The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is subject of great concern at present. In this respect, the genetic toxicity of fenpropathrin ((RS)-α-cyano-3-phenoxybenzyl-2,2,3,3-tetramethyl cyclopropane carboxylate, CAS No.: 39515-41-8), a pyrethroid insecticide, was evaluated in bacterial gene mutation system, chromosome aberration in mammalian cell system andin vivo micronucleus assay with rodents. In bacterial gene mutation assay, no mutagenicity of fenpropathrin (62–5000 μg/plate) was observed inSalmonella typhimurium TA 98, 100, 1535 and 1537 both in the absence and in the presence of S-9 metabolic activation system. In mammalian cell system using chinese hamster lung fibroblast, no clastogenicity of fenpropathrin was also observed both in the absence andin the presence of metabolic activation system in the concentration range of 7–28 μg/ml. And also,in vivo micronucleus assay using mouse bone marrow cells, fenpropathrin also revealed no mutagenic potential in the dose range of 27–105 mg/kg body weight of fenpropathrin (i.p.). Consequently, no mutagenic potential of fenpropathrin was observedin vitro bacterial, mammalian mutagenicity systems andin vivo micronucleus assay in the dose ranges used in this experiment.

Immunoassay development for permethrin residues

Polyclonal antisera were produced in rabbits against two different synthetic immunogens, one of which incorporated 3‐phenoxybenzoic acid (PBA) while the other contained dichlorovinyl cyclopropane carboxylate (CPA). The immunogens were constructed such that the hapten was coupled to the carrier protein through a peptide bond to a six carbon spacing group (6‐amino hexanoic acid, 6‐AHA). Both the anti‐PBA and anti‐CPA antisera obtained were able to detect permethrin when used in an indirect competitive enzyme‐linked immunosorbent assay (IC‐ELISA) format. The detection limits typically obtained with both antisera were 10 mg l‐1with 50% inhibition of antibody binding (ho) at 100mg l‐1. Cross‐reactivity with the pyrethroids cyfluthrin, phenothrin and deltamethrin was observed for both antisera, the degree of which was related to the structural similarity of the compound to the immunizing hapten. Further development of the immunoassay for permethrin was examined through use of the anti‐PBA antiserum. Assay perfo...

Reactions of organomagnesium and organolithium compounds with diethyl (2,3-epoxybutylidene)malonate. A simple synthesis of cyclopropane carboxylates

Reactions of diethyl (2,3-epoxybutylidene)malonate 1 with various magnesium and lithium organics afford lactones 2 – 10 , each containing a cyclopropane fragment.

Efficient Syntheses of (d, l) and (d) Selenomethionine

Abstract Selenomethionine or its protected forms have been prepared from methylselenolates and α-functionalized γ-butyrolactones or α-functionalized methyl cyclopropane carboxylates.

ChemInform Abstract: Synthesis of Synthetic Pyrethroids: Stereoselection in the Synthesis of Cyclopropane Carboxylates

ChemInform Abstract: Synthesis of Synthetic Pyrethroids: Stereoselection in the Synthesis of Cyclopropane Carboxylates

Assay of pyrethroid-hydrolysing esterases using (1,R)-cis-3-(2,2-dibromovinyl)-2,2-dimethyl cyclopropane carboxylates as substrates

1. p-Nitrophenyl-, alpha-naphthyl-, and beta-naphthyl-(1,R)-cis-3-(2,2-dibromovinyl)2,2-dimethyl cyclopropane carboxylates are proposed as pyrethroid-like substrates for the detection of pyrethroid esterases (PyEs). 2. The substrates have been used in a spectrophotometric assay of PyEs and in a staining method to locate PyEs on polyacrylamide electrophoresis.

From tartaric acid to the most biologically active insecticides: Straightforward enantioselective synthesis of pyrethrins

Isopropylidenetriphenylphosphorane reacts with γ-alkoxy α,β-unsaturated esters and produces γ-alkoxy cyclopropane carboxylates. The stereochemistry of the carbon-carbon double bond in the ester has a great influence on the stereo-chemistry of the resulting cyclopropane derivative. This reaction has been successfully used for the synthesis of chrysanthemic acid from diester 2a derived from natural tartaric acid.

From tartaric acid to the most biologically active insecticides: Straightforward enantioselective synthesis of deltamethrin

Isopropylidenediphenylsulfurane reacts with γ-alkoxy αβ—unsaturated esters and produces γ—alkoxy cyclopropane carboxylates. This reaction is almost completely stereospecific and takes place with very high asymmetric induction. It has been successfully applied for the enantioselective synthesis, from natural tartaric acid, of deltamethrin the most active insecticide commercially available.

ChemInform Abstract: Generation and Reactions of Lithiated tert. Butyl and 2,6‐Di(tert‐butyl)‐4‐methylphenyl Cyclopropane Carboxylates.

AbstractLithiation of the cyclopropane carboxylates (I), (XIIIa), or (XIIIb) and subsequent reaction with electrophiles (III)‐(XII) yields the derivatives (II), (XIV), or (XVII).

An Efficient Synthesis of Pyrethroid Insecticides Containing Spiro-fused Cyclopropane Carboxylate

Abstract Among the active pyrethroid insecticides containing various substituted cyclpropanecarboxylates, esters derived from 2,2-dimethyl-5,6-benzospiro [2,4] heptene-1-carboxylic acid (1) have been 1 found to have particularly high activity, Our continuing interest in the synthesis of novel pyrethroid insecticides2 led us to a study of synthetic methodology for constructing spiro-fused systems such as (1).

The effects of cyclopropane carboxylate on hepatic pyruvate metabolism

The effects of cyclopropane carboxylate on gluconeogenesis and pyruvate decarboxylation from [1- 14C]-labeled pyruvate and lactate were investigated in perfused livers from fasted rats. With high concentrations of pyruvate (⩾0.5 m m) in the perfusion medium, infusion of cyclopropane carboxylate inhibited pyruvate decarboxylation and gluconeogenesis by 30 and 40%.respectively. With low, more physiological concentrations of pyruvate (50 μ m) or with lactate (1 m m), cyclopropane carboxylate, at a concentration which elicits maximal inhibition of pyruvate decarboxylation from pyruvate (⩾0.5 m m), did not affect either pyruvate decarboxylation or gluconeogenesis. Evidence is presented for the rapid formation of the coenzyme-A ester of cyclopropane carboxylate in perfused livers. Infusion of l-(−)carnitine (20 m m) prevented the inhibitory effects of cyclopropane carboxylate on pyruvate decarboxylation and gluconeogenesis from pyruvate (⩾0.5 m m. Interestingly, no decrease in the tissue level of cyclopropanecarboxyl-CoA occurs under these conditions. The present study suggests that cyclopropane carboxylate, through a presently ill-defined mediator, inhibits pyruvate decarboxylation and gluconeogenesis by interfering with the pyruvate → oxalacetate → phosphoenolpyruvate → pyruvate cycle when pyruvate (⩾0.5 m m) supports gluconeogenesis.