Cyclopropanecarboxylic Acid Research Articles

The First Cyclopropanation Reaction of Unmasked α,β-Unsaturated Carboxylic Acids: Direct and Complete Stereospecific Synthesis of Cyclopropanecarboxylic Acids Promoted by Sm/CHI3

A samarium-promoted cyclopropanation of unmasked alpha,beta-unsaturated acids is described. This reaction can be carried out on (E)- or (Z)-alpha,beta-unsaturated carboxylic acids. In all cases the process is completely stereospecific and stereoselective. A mechanism has been proposed to explain the cyclopropanation reaction.

Antibacterial Activity of Synthetic Precursors of Podophyllotoxin

Precursors of podophyllotoxin were synthesized and screened for their antibacterial activity. The results proved that ethyl-2-(3'-methyl-4'-methoxybenzoyl)-3-(4" methoxyphenol)-cyclopropane-1-carboxylic acid and Ethyl-2-(3'-methyl-4'-methoxybenzyol-3-1 3", 4"-dimethoxyphenyl)-cyclopropane-carboxylic acid have significant antibacterial activity against Citrobacter sp., Escherchia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella typhi, Shigella sonnei and Streptococcus faecalis. The activity is lower than Ciprofloxacin and equal to Gentamicin and more than Penicillin and Streptomycin.

Cyclanilide Alterations In Growth Of Five Landscape Plant Species During Container Production Are Location Specific

Abstract Five species of tropical and warm temperate shrubs, bush morning glory (Ipomoea carnea N. von Jacquin subsp. fistulosa (K. von Martinus ex J. Choisy) D. Austin), Indian hawthorn (Raphiolepis indica (L.) J. Lindley), tropical hibiscus (Hibiscus rosa-sinensis L. ‘Brilliantissima’), jatropha (Jatropha integerrima N. von Jacquin), and nandina (Nandina domestica C.P. Thunberg), were grown in 2.8-liter (#1) black plastic containers at two contrasting nursery locations and regimes. In College Station, TX, plants were grown in full sun under high fertility conditions, while in Dallas, TX, plants were grown under 40% light exclusion and a lower fertility level. Plants at each location were sprayed to runoff, either once or twice, with a distilled water only control, a Latron B-1956 spreader sticker surfactant at 0.063 mg/liter (0.063 ppm) in distilled water, or cyclanilide [1-(2,4-dichlorophenyaminocarbonyl)-cyclopropane carboxylic acid] at 56, 112, or 223 mg/liter (56, 112, or 223 ppm, respectively) with the Latron surfactant in a distilled water carrier. Half of the plants in all treatments received a single application, while the other half received a second application two to three weeks later. Although growth responses and release of dormancy varied among species and with cyclanilide concentration, plants of most species had greater release of lateral buds from a dormant or quiescent state under the high irradiance and fertility conditions in College Station, compared to the lower irradiance and fertility conditions in Dallas. However, phytotoxicity symptoms as evidenced by lower quality ratings were also more prevalent in College Station. Phytotoxicity was moderate to severe on nearly all jatropha and tropical hibiscus plants exposed to cyclanilide. Toxicity symptoms and significant growth reductions were present on several species at 112 or 223 mg/liter (112 or 223 ppm, respectively). A second application usually increased the effects on growth responses at all concentrations and often induced phytotoxicity symptoms at 56 mg/liter (56 ppm). The disparate responses between the two locations suggest the importance of local growing conditions on the potential efficacy and predictability of responses to cyclanilide applications.

Mechanism of the decarboxylative rearrangement of α-(carbonyl)cyclopropane carboxylic acids to 2-substituted-4,5-dihydrofurans

Previously we described the thermal decarboxylation of 1-(cyclopropylcarbonyl) cyclopropane carboxylic acid at 120 o C yielded 2-cyclopropyl-4,5-dihydrofuran instead of the expected dicyclopropyl ketone. The proposed mechanism proceeded through an initial ring opening of the 1,2-disubstitued cyclopropyl moiety leading to an α-allyl-β-keto acid system, specifically in this case α-(cyclopropylcarbonyl)-3-butenoic acid. In this paper we demonstrate that an α(carbonyl)-3-butenoic acid when thermally decarboxylated rearranges to the substituted 4,5dihydrofuran. Additionally, it was demonstrated that the decarboxylation and rearrangement are simultaneous and not a stepwise decarboxylation followed by rearrangement and ring closure.

Reaction Pathways of the Diketonitrile Degradate of Isoxaflutole with Hypochlorite in Water

Isoxaflutole (IXF; Balance) belongs to a new class of isoxazole herbicides. Isoxaflutole has a very short half-life in soil and rapidly degrades to a stable and phytotoxic degradate, diketonitrile (DKN). DKN was previously discovered to rapidly react with hypochlorite (OCl-) in tap water, yielding the benzoic acid (BA) degradate as a major product, but the complete reaction pathway and mechanism have not been elucidated. Thus, the objectives of this work were to (1) determine the stoichiometry of the reaction between DKN and OCl-; (2) identify products in addition to BA; and (3) propose a complete pathway and reaction mechanism for oxidation of DKN by OCl-. Stoichiometry of the reaction showed a molar ratio of OCl-/DKN of 2. In addition, two previously uncharacterized chlorinated intermediates were identified under conditions in which OCl- was the limiting reactant. The proposed chemical structure of a chlorinated benzoyl intermediate was inferred from a series of HPLC/MS and HPLC/MS/MS experiments and the use of mass spectral simulation software. A chlorinated ketone intermediate was also identified using ion trap GC/MS. Two additional end products were also identified: cyclopropanecarboxylic acid (CPCA) and dichloroacetonitrile (DCAN). On the basis of the reaction stoichiometry, the structure of the chlorinated intermediates, and the identification of the products, two reaction pathways are proposed. Both pathways involve a two-step nucleophilic attack and oxidation of the diketone structure of DKN, leading to formation of BA, DCAN, and CPCA.

3,3,5‐Trimethylcyclohexanols and derived esters: green synthetic procedures, odour evaluation and in vitro skin cytotoxicity assays1

The alcohols 3,3,5-trimethylcyclohexanols (cis, trans epimers, cosmetic fragrance) and some derived esters, potential and well-known actives in the cosmetic field, such as Homosalate, were synthesized using fast solvent-free methodologies with the aim of renewing and simplifying the conventional procedures. The alcohols were prepared by reduction of 3,3,5-trimethylcyclohexanone (dihydroisophorone) with sodium borohydride/alumina in solid state. The esters from propanoic, butanoic, octanoic, 10-undecenoic, cyclopropanecarboxylic, mandelic and salicylic acids were synthesized with microwave-mediated solvent-free procedures under acidic and basic catalysis. Several experiments were carried out to study advantages and limits of the selected methodologies and the results are reported. Microwave irradiation was carried out using a scientific monomode reactor. In order to evaluate the cosmetic interest of the studied compounds, the sweet-scented substances were submitted to an odour evaluation test; the most promising fragrances and the ester from 10-undecenoic acid, as an example of lipophilic derivatives, were tested to assess their in vitro skin toxicity. Résumé

Structural basis for the inhibition of Aurora A kinase by a novel class of high affinity disubstituted pyrimidine inhibitors

The 2.25 Å crystal structure of a complex of Aurora A kinase (AIKA) with cyclopropanecarboxylic acid-(3-(4-(3-trifluoromethyl-phenylamino)-pyrimidin-2-ylamino)-phenyl)-amide 1 is described here. The inhibitor binding mode is novel, with the cyclopropanecarboxylic acid moiety directed towards the solvent exposed region of the ATP-binding pocket, and several induced structural changes in the active-site compared with other published AIK structures. This structure provides context for the available SAR data on this compound class, and could be exploited for the design of analogs with increased affinity and selectivity for AIK.

Assessing Nicaraguan Farm Families’ Exposure to Pyrethroids Using Urinary Biomarkers

P-469 Introduction: Pyrethroids are widely used in Nicaragua. In agriculture, deltamethrin and cypermethrin are used to control pests in sesame, coffee, vegetables, corn, peanut, and tobacco crops. Public health agencies use nets impregnated with cypermethrin or alfa-cypermethrin domiciliary application to control diseases transmitted by mosquito vectors (malaria and dengue fever). The purpose of this study is to quantitatively assess exposure to the pyrethroid pesticides in Nicaraguan agricultural families using urinary biomarkers. Methods: A total of 10 banana plantation workers’ families and 7 small farmers’ families were recruited to participate in a cross sectional study with multiple day sampling. Urine samples were taken from one adult and one child per family 3 times a day for 3 consecutive days. The sampling schedule was unrelated to recent pyrethroid application. The children’s ages ranged between 2 to 12. In the banana plantations, 58 urine samples were collected from the adults, and 56 samples were collected from their children. In small farms, 53 urine samples were collected from the adults, and 54 samples were collected from their children. Urine samples collected in Nicaragua were shipped to the Center for Disease Control and Prevention (CDC) in Atlanta, GA for analysis. Results: The metabolites 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), cis-3-(2,2-dichlorovinyl)2-2-dimethyl cyclopropane carboxylic acid (cis-DCCA), trans-3-(2,2-dichlorovinyl)2-2-dimethyl cyclopropane carboxylic acid (trans-DCCA) and cis-3(2,2-dibromovinyl)2,2dimethylcyclopropane carboxylic acid (DBCA) were detected in 98, 4, 96, 94 and 2% of the samples, respectively. In banana plantation families PBA urine levels ranged from 0.23 to 21.27 μg/l in adults and from the LOD to 4.36 μg/ in children, 4F3PBA urine levels ranged from 0.27 to 0.41 μg/l in adults and 0.44 to 1.25 μg/l in children, cis-DCCA from the LOD to 8.41μg/l in adults and LOD to 3.10 μg/l in children, trans-DCCA ranged between LOD to 14.04 μg/l in adults and LOD to 5.13 μg/l in children, DBCA from 24.27 to 31.32 μg/l in adults and in children only in one sample was quantified, the level was 22.94 μg/l. In small farmers′ families PBA urine levels ranged from LOD to 3.35 μg/l in adults and LOD to 4.13 μg/ in children, cis-DCCA LOD to 1.50 μg/l in adults and LOD to 1.92 μg/l in children, trans-DCCA ranged from LOD to 2.18 μg/l in adults and LOD to 3.82 μg/l in children. The metabolites 4F3PBA and DBCA were not detected in this group. Discusion and conclusions: The urine levels of the general metabolites of pyrethroids, PBA, cis-DCCA, trans-DCCA and DBCA, exceed published background levels. As this population had no recent occupational pyrethroid exposure, a possible source of exposure could be indoor contamination resulting from sanitary campaigns.

SAR studies of 3-arylpropionic acids as potent and selective agonists of sphingosine-1-phosphate receptor-1 (S1P 1) with enhanced pharmacokinetic properties

Structure–activity relationship (SAR) studies of 3-arylpropionic acids—a class of novel S1P 1 selective agonists—by introducing substitution to the propionic acid chain and replacing the adjacent phenyl ring with pyridine led to a series of modified 3-arylpropionic acids with enhanced half-life in rat. These analogs (e.g., cyclopropanecarboxylic acids) exhibited longer half-life in rat than did unmodified 3-arylpropionic acids. This result suggests that metabolic oxidation at the propionic acid chain, particularly at the C3 benzylic position of 3-arylpropionic acids, is probably responsible for their short half-life in rodent.

Chemoenzymatic synthesis of enantiopure geminally dimethylated cyclopropane-based C2- and pseudo- C2-symmetric diamines

Enantiopure (−)-(1 S,3 S)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxamide 2 and (+)-(1 R,3 R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxylic acid 3 were easily obtained from a multigram scale biotransformation of racemic amide or nitrile in the presence of Rhodococcus erythropolis AJ270 whole cell catalyst under very mild conditions. Coupled with efficient and convenient chemical manipulations, comprising mainly of the Curtius rearrangement, oxidation, and reduction reactions, chiral C 2-symmetric (1 S,2 S)-3,3-dimethylcyclopropane-1,2-diamine 6 and ((1 R,3 R)-3-(aminomethyl)-2,2-dimethylcyclopropyl)methanamine 8 and pseudo- C 2-symmetric (1 S,3 S)-3-(aminomethyl)-2,2-dimethylcyclopropanamine 11 were prepared. These were also transformed into the corresponding chiral salen derivatives 12, 13, and 14, respectively, in almost quantitative yields.

Compuestos químicos inductores de resistencia contra Colletotrichum gloeosporioides en mangó

Se evaluaron varios compuestos químicos inductores de resistencia en la interacción entre mangó (Mangifera indica L.) y el patógeno, agente causal de la antracnosis, Colletotrichum gloeosporioides. Los compuestos evaluados fueron ácido salicílico, ácido isonicotínico, ácido benzo (1,2,3) tiadiazol-7-carbotiónico áster de S-metilo (Actigard®) y otros compuestos químicos estructuralmente similares como el ácido nicotínico, el dinucleótido de adenina de ácido nicotínico, el áster de etilo del ácido isonicotínico, el N-óxido de ácido isonicotínico, el ácido benzoico y el benzoato de sodio. En el laboratorio antes de la inoculación, estos compuestos se asperjaron hasta la saturación sobre pedazos de hojas y frutas de mangó. En condiciones de laboratorio, el tamaño de las lesiones causadas por C. gloeosporioidesen pedazos de hojas y frutas de mangó se redujo significativamente (P < 0.10) a concentraciones que fluctuaron entre 10-12 M a 10-6 M de ácido salicílico (SA), 10-18 M y 10-14 M de ácido isonicotínico (INA), 10-17 M a 10-2 M de Actigard® y 10-10 M de ácido benzoico (BA). El ácido salicílico, INA y BA causaron toxicidad en las hojas a concentraciones que fluctuaron entre 10-1 a 10-3 M. Los compuestos químicos que indujeron resistencia en condiciones de laboratorio se evaluaron en árboles de mangó de seis meses de edad en condiciones de umbráculo. Ninguno de los compuestos químicos evaluados redujo significativamente (P < 0.05) el tamaño de la lesión causada por C. gloeosporioides. Otros agentes químicos inductores de resistencia que no fueron evaluados durante estos estudios, tales como probenazol, derivados ciclopropanos de ácido carboxílico, aminoácidos no-proteícos [β-ácido aminobutírico (BABA) y Ï’-ácido aminobutírico (GABA)] y Phytogard®, se deben evaluar individualmente y en combinación para clarificar la ausencia de inducción de resistencia en los tejidos del mangó.

Timing Cyclanilide and Cytokinin Applications in the Nursery to Obtain Desired Lateral Branch Height in Apple and Sweet Cherry Trees

The height above the bud union at which induced feathers develop on fruit trees in the nursery is an important determinant of tree quality for an intended market. The bioregulators cyclanilide (CYC; Bayer Environmental Science, Research Triangle Park, NC) and a proprietary formulation of 6-benzyladenine and gibberellins A4 and A7 (Promalin [PR]; Valent BioSciences, Walnut Creek, CA) affected the final height above the union of the lowest induced sylleptic shoot (feather) differently in apple and sweet cherry trees in the nursery. In apple, both products resulted in the lowest induced feather developing at approximately 4 to 20 cm below the height of the central leader shoot tip at the time of bioregulator application. In sweet cherry, the lowest induced feather typically originated starting approximately 2 to 20 cm above the central leader shoot tip height at the time of bioregulator application. Nursery tree height can serve as a suitable criterion for timing bioregulator applications to obtain feathers starting within a specific range of height above the bud union as long as species-specific feathering response characteristics are taken into account. Chemical names used: 1-(2,4-dichlorophenylaminocarbonyl)-cyclopropane carboxylic acid (Cyclanilide), N-(phenylmethyl)-1H-purine-6-amine + gibberellins A4A7 (Promalin), polyoxyethylenepolypropoxypropanol, dihydroxypropane, 2-butoxyethanol (Regulaid).

Effect of Cyclanilide, Ethephon, Auxin Transport Inhibitors, and Temperature on Whole Plant Defoliation

Whole plant defoliation studies were performed using dark red kidney bean (Phaseolus vulgaris L.) to compare the effect of cyclanilide [1‐(2,4‐dichlorophenylaminocarbonyl)‐cyclopropane carboxylic acid], ethephon (2‐chloroethylphosphonic acid), auxin transport inhibitors, and temperature on leaf abscission. Ethephon induced bean leaf defoliation, but ethephon combined with cyclanilide induced greater defoliation than ethephon alone. The response was dose dependent, as 0.067 kg/ha ethephon alone did not induce defoliation, but when combined with an equal rate of cyclanilide induced 63% defoliation five days after treatment (DAT). In addition, combining auxin transport inhibitors at 0.140 kg a.i./ha with 0.067 kg a.i./ha ethephon induced 50 to 52% defoliation, 5 DAT. Ethephon‐induced defoliation was more temperature sensitive than the combination of cyclanilide with ethephon. Ethephon alone (0.067 kg a.i./ha) induced 26% defoliation 5 DAT at the highest tested temperature (30/26°C, day/night), but cyclanilide combined with ethephon induced 75 to 85% defoliation at all tested temperatures (except at 16/14°C, the lowest). These results indicate that cyclanilide is an ethephon synergist because it enhanced ethephon activity, even at low temperatures. These results support the model that ethylene released by ethephon induces abscission, and suggests that inhibition of auxin transport or auxin signaling will increase the effect of ethylene on the process of leaf abscission. Because of the similarities to the activity to 1‐N‐naphthylphthalamic acid (NPA) and 2,3,4‐triiodobenzoic acid (TIBA) in vivo, cyclanilide may act as an auxin transport inhibitor.

A New Entry to Enantiopure Polysubstituted Cyclopropanes: Stereoselective Denitrogenation of Sulfinylpyrazolines under Yb(OTf)3 Catalysis

[Structure: see text] Chemoselective and completely stereoselective denitrogenation of optically pure pyrazolines, derived from 3-sulfinylfuran-2(5H)-ones, into cyclopropanes can be achieved under substoichiometric Yb(OTf)3 catalysis. Reactions evolve in almost quantitative yields with complete retention of the configuration at both carbons flanking the nitrogen atoms. The resulting enantiomerically pure polysubstituted cyclopropanes, containing up to five substituens, can be desulfinylated with Ra-Ni providing polysubstituted cyclopropanecarboxylic acid derivatives.

Synthesis and characterization of new polymethacrylate bearing cyclopropane ring as side group

A cyclopropanation reaction of allylmethacrylate ( 1) with ethyldiazoacetate ( 2) lead to the formation of 2-(2-methyl-acryloyloxymethyl)-cyclopropanecarboxylic acid ethyl ester ( 3) as a mixture of cis/trans isomers in molar ratio 2:1. The cis isomer could be selectively hydrolyzed by use of Pig liver esterase (PLE). An isolated cis-2-(2-methyl-acryloyloxymethyl)-cyclopropanecarboxylic acid ( 4) exhibited optical activity. The monomer 3 was easily polymerized using AIBN and benzopinacol as free radical initiators at 65 and 130 °C, respectively. 1H NMR and FT-IR analyses confirmed the presence of the chemically stable cyclopropane ring in both monomer and polymers. The obtained polymers were also characterized by GPC and DSC measurements. A depolymerization behaviour was observed heating the polymers at 200–250 °C. The regeneration of starting cis/trans isomers of 3 can be taken as a proof of the high thermal stability of the cyclopropane ring.

Cyclanilide Induces Lateral Branching in Sweet Cherry Trees

A new bioregulator, cyclanilide (CYC, Bayer Environmental Science, Research Triangle Park, NC 27709), was compared with a proprietary formulation of 6-benzyladenine and gibberellins A4 and A7 [Promalin (PR), Valent BioSciences, Walnut Creek, Calif.] for branching effects on sweet cherry trees. CYC stimulated the formation of lateral shoots on current-season's shoot growth under both orchard and nursery conditions. In the nursery CYC was as effective or better for feathering compared to PR in all cherry cultivars tested. There were no synergistic effects of CYC/PR tank mixes on feather development. Crotch angles of induced feathers were not different from the angles of feathers that formed spontaneously. The growth of CYC-induced feathers was sufficient to produce acceptable quality feathered trees. Trunk caliper of nursery trees was either not affected or reduced to a very minimal degree. CYC is effective for lateral branch induction in sweet cherry, especially in the nursery. Chemical names used: 1-(2,4-dichlorophenylaminocarbonyl)-cyclopropane carboxylic acid (cyclanilide); N-(phenylmethyl)-1H-purine-6-amine + gibberellins A4 and A7 (Promalin); polyoxyethylenepolypropoxypropanol, dihydroxypropane, 2-butoxyethanol (Regulaid).

Biodegradation of Allethrin, a Pyrethroid Insecticide, by an Acidomonas Sp.

Allethrin is a major mosquito repellent agent. To degrade allethrin present in used mats and the environment, a bacterium capable of utilizing allethrin was isolated. This isolate, an Acidomonas sp., grew in minimal medium with 16 mM: allethrin as sole source of carbon and degraded >70% of it in 72 h, with negligible residual metabolites in the medium. Culture filtrates collected after 48 h and 72 h showed presence of (i) cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methyl-1-propenyl), (ii) 2-ethyl-1,3-dimethyl-cyclopent-2-ene-carboxylic acid (iii) chrysanthemic acid and (iv) allethrolone [2-cyclopenten-l-one, 4-hydroxy-3-methyl-2(-2-propenyl)] as the major metabolites with 2 minor metabolites. Allethrin is thus metabolized by a hydrolytic pathway followed by oxidation and dehydrogenation.

Biodegradation of beta-cyfluthrin by Pseudomonas stutzeri strain S1

beta-Cyfluthrin [alpha-cyano-4-fluoro-3-phenoxybenzyl-3(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate] pesticide has been in agricultural use in the recent years for controlling Lepidopteran pests affecting solanaceous crops. The extensive use of synthetic pyrethroids like beta-cyfluthrin has resulted in wide spread environmental contamination. The purpose of this study was to isolate bacteria from soil and to determine their ability to degrade beta-cyfluthrin and identify the intermediates in culture broth using spectroscopy. An aerobic bacterium capable of degrading beta-cyfluthrin was isolated by enrichment culture. The 16S ribosomal DNA sequence of the isolate (strain S1) had 100% identity to the sequence from Pseudomonas stutzeri. Finally products formed during degradation of beta-cyfluthrin have been identified as alpha-cyano-4-fluoro-3-phenoxybenzyl-3(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylate (M.W. 341); 4-fluoro-3-phenoxy-alpha-cyanobenzyl alcohol (M.W. 243) and 3(2,2-dichlorovinyl)-2,2-dimethyl cyclopropanecarboxylic acid (M.W. 208).

Halogen Effects in Robinson—Gabriel Type Reaction of Cyclopropanecarboxylic Acid N′‐Substituted‐Hydrazides with PPh3/CX4.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of 17-epi-Calcitriol from a Common Androstane Derivative, Involving the Ring B Photochemical Opening and the Intermediate Triene Ozonolysis

An efficient synthesis of 17-epi-calcitriol 2, an epimer of natural hormone, via 17-epi-cholesterol 5a is described. Synthesis of 5a includes palladium-catalyzed cyclopropanation of the common androstane derivative 7 with an alkyl diazoacetate, reductive fission of the less shielded side of cyclopropane carboxylic acid esters 6, oxidation of the products into acid 11a, and alkylation of ester 11b. Photolysis of 7,8-dedydro-17-epi-25-hydroxycholesterol 19b and consecutive thermal rearrangement gave a mixture of several products that was subjected to ozonolysis to provide, after chromatography, hydroxy ketone 3a. The silyl derivative 3b was coupled with the respective ring A building block.