- Metabolism of (S)-bioallethrin and related compounds in humans
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Chrysanthemate insecticides like (S)-bioallethrin, natural pyrethins, and related pyrethroids are subjected to extensive hydrolytic and oxidative degeneration by the mammalian metabolism, leading to a complex series of metabolites partially conjugated and finally eliminated in the urine. The major oxidation products of chrysanthemic acid, cis-(E)- and trans-(E)-chrysanthemumdicarboxcylic acid (cis-(E) and trans-(E)-CDCA), were synthesized and their structures were established by nuclear magnetic resonance spectrometry (H1-NMR) and mass spectrometry (MS). Diastereoselective separation was by high performance liquid chromatography (HPLC) and capillary gas chromatography (GC). An analytical method for extraction and identification of CDCA from human urine was developed. Quantitation was by gas chromatography and electron-impact mass spectrometry (GC/MS). The limit of detection was 20 μg/l for cis-(E)-CDCA and 10 μg/l for trans-(E)-CDCA. To test the applicability of the presented method, urine samples of humans exposed to (S)-bioallethrin were investigated. Urinary peak excretion of trans-(E)-CDCA occurred within 24 h after exposure. Copyright (C) 1999 Elsevier Science Ireland Ltd.
- Leng, Gabriele,Kuehn, Karl-Heinz,Wieseler, Brigitte,Idel, Helga
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- Total Syntheses of All Six Chiral Natural Pyrethrins: Accurate Determination of the Physical Properties, Their Insecticidal Activities, and Evaluation of Synthetic Methods
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Chiral total syntheses of all six insecticidal natural pyrethrins (three pyrethrin I and three pyrethrin II compounds) contained in the chrysanthemum (pyrethrum) flower were performed. Three common alcohol components [(S)-cinerolone, (S)-jasmololone, and (S)-pyrethrolone] were synthesized: (i) straightforward Sonogashira-type cross-couplings using available (S)-4-hydroxy-3-methyl-2-(2-propynyl)cyclopent-2-en-1-ones (the prallethrin alcohol) for (S)-cinerolone (overall 52% yield, 98% ee) and (S)-pyrethrolone (overall 54% yield, 98% ee) and (ii) traditional decarboxylative-aldol condensation and lipase-catalyzed optical resolution for (S)-jasmololone (overall 16% yield, 96% ee). Two counter acid segments [(1R,3R)-chrysanthemic acid (A) and (1R,3R)-second chrysanthemic acid precursor (B)] were prepared: (i) C(1) epimerization of ethyl (±)-chrysanthemates and optical resolution using (S)-naphthylethylamine to afford A (96% ee) and (ii) concise derivatization of A to B (96% ee). All six pyrethrin esters (cinerin I/II, jasmolin I/II, and pyrethrin I/II) were successfully synthesized utilizing an accessible esterification reagent (TsCl/N-methylimidazole). To investigate the stereostructure-activity relationship, all four chiral stereoisomers of cinerin I were synthesized. Three alternative syntheses of (±)-jasmololone were investigated (methods utilizing Piancatelli rearrangement, furan transformation, and 1-nitropropene transformation). Insecticidal activity assay (KD50 and IC50) against the common mosquito (Culex pipiens pallens) revealed that (i) pyrethrin I > pyrethrin II, (ii) pyrethrin I (II) > cinerin I (II) ? jasmolin I (II), and (iii) "natural" cinerin I ? three "unnatural" cinerin I compounds (apparent chiral discrimination).
- Ashida, Yuichiro,Kawamoto, Momoyo,Matsuo, Noritada,Moriyama, Mizuki,Tanabe, Yoo
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p. 2984 - 2999
(2020/03/24)
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- Method for preparing chiral trans-chrysanthemic acid
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The invention provides a method for preparing chiral trans-chrysanthemic acid, belongs to the field of organic synthesis, and relates to a method for synthesis of chiral ethyl chrysanthemumate from 2,5-dimethyl-2,4-hexadiene and ethyl diazoacetate by an asymmetric cyclopropanation reaction and for hydrolysis to form chiral chrysanthemic acid. A chiral copper catalyst adopted is prepared in situ from a copper salt and a chiral tridentate P,N,N-ligand in various polar and non-polar solvents. The chiral trans-chrysanthemic acid can be conveniently synthesized, and the percentage of enantiomeric excess is as high as 95%. The method has the characteristics such as simple operation, easy availability of raw materials, wide application range of substrates and high enantioselectivity.
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Paragraph 0034-0044; 0051-0083; 0088-0091; 0096-0099
(2019/10/29)
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- Cyclopropanation of Terminal Alkenes through Sequential Atom-Transfer Radical Addition/1,3-Elimination
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An operationally simple method to affect an atom-transfer radical addition of commercially available ICH2Bpin to terminal alkenes has been developed. The intermediate iodide can be transformed in a one-pot process into the corresponding cyclopropane upon treatment with a fluoride source. This method is highly selective for the cyclopropanation of unactivated terminal alkenes over non-terminal alkenes and electron-deficient alkenes. Due to the mildness of the procedure, a wide range of functional groups such as esters, amides, alcohols, ketones, and vinylic cyclopropanes are well tolerated.
- Tappin, Nicholas D. C.,Michalska, Weronika,Rohrbach, Simon,Renaud, Philippe
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supporting information
p. 14240 - 14244
(2019/08/26)
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- Syntheses of racemic and scalemic cis-chrysanthemic acid from β,γ-unsaturated cyclohexanol
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2,2,5,5-Tetramethylcyclohexane-1,3-dione is a valuable starting-material precursor of cis-chrysanthemic acid. The (1S)-stereoisomer is a precursor of pyrethrin I, the most active natural insecticide from Chrysanthemum cinerariifolium, whereas the (1R)-stereoisomer is efficiently transformed to deltamethrin, the most active commercially available pyrethroid insecticide. Several intermediates have been identified and used with variable success for that purpose.
- Krief, Alain,Jeanmart, Stéphane,Gondal, Humaira Y.,Kremer, Adrian
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p. 2123 - 2167
(2013/02/23)
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- Identification of the catalytic residues of carboxylesterase from arthrobacter globiformis by diisopropyl fluorophosphate-labeling and site-directed mutagenesis
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The role of amino acid residues in the enzymatic activity of carboxylesterase from Arthrobacter globiformis was analyzed by diisopropyl fluorophosphate (DFP) labeling and site-directed mutagenesis. The electrospray ionization mass spectrometric (ESI-MS) analysis of the esterase, covalently labeled by DFP, showed stoichiometric incorporation of the inhibitor into the enzyme. The further comparison of endopeptidase-digested fragments between native and DFP-labeled esterase by fast atom bombardment mass spectrometric (FAB-MS) analysis as well as site-directed mutagenesis indicated that Ser59 in the consensus sequence Ser-X-X-Lys, which is conserved exclusively in penicillin-binding proteins and some esterases, served as a catalytic nucleophile. In addition, the results obtained from analysis of the mutants at position 62 suggested the importance of the basic amino acid side chain at this position, and suggested the significance of this residue acting directly as a general base rather than its involvement in the maintenance of the optimum hydrogenbonding network at the active site.
- Nishizawa, Masako,Yabusaki, Yoshiyasu,Kanaoka, Masaharu
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experimental part
p. 89 - 94
(2011/09/30)
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- Unprecedented dual reactivity of anhydrous potassium hydroxide in cascade cyclopropannelation/Haller-Bauer-scission/Grob-fragmentation reactions
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We report an unprecedented type of reactivity of 'anhydrous potassium hydroxide' ('APH') in which it plays, over a large variety of related educts, sequentially the role of base and nucleophile. Some insight into the structure of reactive species as well as comparative reactivity of related reagents prepared by fusion of commercially available potassium hydroxide or by adding stoichiometric amount of water to potassium hydride is provided.
- Krief, Alain,Kremer, Adrian
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body text
p. 4306 - 4309
(2010/09/20)
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- A practical method for O-acylation of N -hydroxythiazole-2(3 H)-thiones
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O-Acylation of 4- and 4,5-substituted N-hydroxythiazole-2(3H)-thiones occurred in solutions of acetone upon treatment with solid K2CO3 and a variety of neat acyl chlorides (primary, secondary, and tertiary alkyl, aryl; 60-87% yield; ～10 g scale).
- Schur, Christine,Gross, Andreas,Hartung, Jens
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experimental part
p. 538 - 542
(2010/06/13)
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- Practical method for crystalline-liquid resolution of chrysanthemic acids utilizing chiral 1,1′-binaphthol monoethyl ethers directed for process chemistry
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We have developed an efficient practical resolution method for (1R,3R)-trans-chrysanthemic acid 1 and (1R,3S)-trans-2,2-dimethyl-3-(2,2-dichloroethenyl)cyclopropanecarboxylic acid 2, based on the preliminary results of the simpler analogues, (1R)-2,2-dichlorocyclopropanecarboxylic acid 3 and (1R)-2,2-dimethylcyclopropanecarboxylic acid 4, using a crystalline-liquid separation procedure (without column chromatography) with chiral 1,1′-binaphthol monoethyl ethers (R)-5b as the key auxiliary. Direct esterifications of 1, 2, 3, and 4 with (R)-5b gave four sets of (1R)- and (1S)-diastereomeric esters 8, 9, 6, and 7, respectively, with markedly different melting points. All of these diastereomers were easily obtained using a simple and one-step crystalline-liquid separation. The separated diastereomers 8 and 9 were easily hydrolyzed to the desired enantiopure acids 1 (>98%) and 2 (>99%), respectively, with recovery of (R)-5b (>90%).
- Atago, Takayuki,Tanaka, Akihiro,Kawamura, Tomoyuki,Matsuo, Noritada,Tanabe, Yoo
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experimental part
p. 1015 - 1019
(2009/09/30)
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- Selected regiocontrolled transformations applied to the synthesis of (1S)-cis-chrysanthemic acid from (1S)-3,4-epoxy-2,2,5,5-tetramethylcyclohexanol
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(1S)-cis-Chrysanthemic acid has been prepared in a few steps with complete control of the relative and absolute stereochemistry using regiocontrolled epoxide ring opening, diol mono-oxidation and cyclopropanation. The Royal Society of Chemistry.
- Krief, Alain,Gondal, Humaira Y.,Kremer, Adrian
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scheme or table
p. 4753 - 4755
(2009/03/12)
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- Practical copper-catalyzed asymmetric synthesis of chiral chrysanthemic acid esters
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Practical copper salicylaldimine complex catalysts have been developed for the asymmetric synthesis of chiral chrysanthemic acid esters by the cyclopropanation reaction of 2,5-dimethyl-2,4-hexadiene with tert-butyl diazoacetate. First, the effects of the substituents on the salicylaldehyde moiety in the copper salicylaldimine complex (copper Schiff base complex) on the catalytic activity and the stereoselectivities were investigated. As a result, a substitution of hydrogen at the 5-position with the nitro group on the salicylaldehyde moiety was found to enhance the catalytic efficiency. In addtition, a combination catalyst of the copper Schiff base complex with Lewis acid was found to also enhance the catalytic efficiency and achieved 90% chemical yield and 91% ee at 20 °C with 0.1 mol % catalyst loading. Furthermore, the asymmetric induction mechanism of the cyclopropanation reaction catalyzed by the copper Schiff base complex was studied using density functional calculations.
- Itagaki, Makoto,Suenobu, Katsuhiro
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p. 509 - 518
(2012/12/31)
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- PROCESS FOR OBTAINING ENANTIOMERS OF CHRYSANTHEMIC ACID
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A new process is described, easy to perform on industrial scale, with high yield, for obtaining enantiomers of chrysanthemic acid starting from mixtures containing them. The process involves reacting said mixtures with enantiomers of 2- dimethylamino-1-phenyl-1 ,3-propanediol (DMPP) and 2-dimethylamino-1-[4- (methylthio)phenyl]propane-1 ,3-diol (MTDP) as chiral selectors. The invention includes salts of chrysanthemic acid with the aforesaid chiral selectors as process intermediates. The process allows operation in a single solvent rather than in solvent mixtures difficult to recover and reuse, and the final crystallization product does not incorporate molecules of solvent. The bases used are then recovered and reused in subsequent separations.
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Page/Page column 15-17
(2008/06/13)
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- Chemoenzymatic synthesis of enantiopure geminally dimethylated cyclopropane-based C2- and pseudo-C2-symmetric diamines
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Enantiopure (-)-(1S,3S)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropanecarboxamide 2 and (+)-(1R,3R)-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 C2-symmetric (1S,2S)-3,3-dimethylcyclopropane-1,2-diamine 6 and ((1R,3R)-3-(aminomethyl)-2,2-dimethylcyclopropyl)methanamine 8 and pseudo-C2-symmetric (1S,3S)-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.
- Feng, Guo-Qiang,Wang, De-Xian,Zheng, Qi-Yu,Wang, Mei-Xiang
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p. 2775 - 2780
(2007/10/03)
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- Nitrile biotransformation for highly enantioselective synthesis of 3-substituted 2,2-dimethylcyclopropanecarboxylic acids and amides
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Biotransformations of differently configured 2,2-dimethyl-3-substitued-cyclopropanecarbonitriles were studied using a nitrile hydratase/amidase-containing Rhodococcus sp. AJ270 whole-cell catalyst under very mild conditions. Although all of the cis-3-aryl-2,2-dimethylcyclopropanecarbonitriles appeared inert toward the biocatalyst, a number of racemic trans-isomers efficiently underwent a highly enantioselective hydrolysis to produce (+)-(1R,3R)-3-aryl-2,2-dimethylcyclopropanecarboxylic acids and (-)-(1S,3S)-3-aryl-2,2-dimethylcyclopropanecarboxamides in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of 1R-enantioselective nitrile hydratase and amidase, with the later being a dominant factor. The influence of the substrates on both reaction efficiency and enantioselectivity was discussed in terms of steric and electronic effects. Coupled with chemical transformations, biotransformations of nitriles provided convenient syntheses of optically pure geminally dimethyl-substituted cyclopropanecarboxylic acids and amides, including chrysanthemic acids, in both enantiomeric forms.
- Wang, Mei-Xiang,Feng, Guo-Qiang
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p. 621 - 624
(2007/10/03)
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- Role of the solvent in optical resolution of trans-chrysanthemic acid via diastereomeric salt formation with (1R,2R)-1-(4-nitrophenyl)-2-dimethylaminopropane-1,3-diol
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Optical resolution of trans-chrysanthemic acid via diastereomeric salt formation with (1R,2R)-1-(4-nitrophenyl)-2-dimethylaminopropane-1,3-diol (DMAD) has been studied in different solvents. Ether type solvents containing MeOH were found to be preferred. The role of MeOH was interpreted on the basis of power and single crystal X-ray diffraction and DSC/TG measurements. We found that MeOH was incorporated into the crystals of the less soluble diastereomer salt of the 1R acid with DMAD in a non-stochiometric amount and postulated to promote nucleation and crystal growth.
- Kozsda-Kovacs, Eva,Keserue, Gyoergy Miklos,Boecskei, Zsolt,Szilagyi, Ildiko,Simon, Kalman,Bertok, Bela,Fogassy, Elmer
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p. 149 - 153
(2007/10/03)
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- Enzyme catalysed kinetic resolution of racemic 2,2-dimethyl-3-(2,2- disubstituted vinyl) cyclopropane carboxylic acids anchored on polymer supports
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Kinetic resolution of trans-substituted cyclopropane carboxylic acids anchored on a solid support by lipase is described.
- Nanda,Bhaskar Rao,Yadav
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p. 5905 - 5908
(2007/10/03)
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- Electron transfer photochemistry of chrysanthemol: An intramolecular S(N)2' reaction of a vinylcyclopropane radical cation
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The electron transfer photochemistry of optically pure (1R,3S)-(+)-cis-chrysanthemol (cis-2) results in the formation of (R)-5-(1-(p-cyanophenyl)-1-methylethyl)-2,2-dimethyl oxacyclohex-3-ene (4) with significant retention of optical activity. The product is rationalized via nucleophilic attack of the alcoholic function of the radical cation on the terminal carbon of the vinyl group with simultaneous replacement of an isopropyl radical as an intramolecular leaving group in an apparent S(N)2' reaction. This mode of attack is unprecedented in vinylcyclopropane radical cations and is interpreted as evidence for the significant role that relief of ring strain and its avoidance play in determining the course of nucleophilic capture in radical cationic systems.
- Herbertz, Torsten,Roth, Heinz D.
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p. 10954 - 10962
(2007/10/03)
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- Lipase catalysed kinetic resolution of racemic (±)2,2-dimethyl-3-(2-methyl-1-propenyl)-cyclopropane carboxyl esters
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Optically active (1R)(-) and (1S)(+)-trans-Chrysanthemic acid and its esters were prepared from corresponding racemic methyl ester by lipase mediated enantioselective hydrolysis, is described.
- Bhaskar Rao,Rehman,Krishnakumari,Yadav
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p. 2611 - 2614
(2007/10/02)
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- Purification and Some Properties of Carboxylesterase from Arthrobacter globiformis; Stereoselective Hydrolysis of Ethyl Chrysanthemate
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An esterase with excellent stereoselectivity for (+)-trans-ethyl chrysanthemate was purified to homogeneity from Arthrobacter globiformis SC-6-98-28.The purified enzyme hydrolyzed a mixture of ethyl chrysanthemate isomers stereoselectively to produce (+)-trans-acid with 100percent stereoisomeric purity.The apparent molecular weight of the purified enzyme was 43,000 on SDS-polyacrylamide gel electrophoresis, and 94,000 on gel filtration chromatography.The optimum conditions for the ester hydrolysis were pH 10.0 at 45 deg C.The purified esterase hydrolyzed short-chain fatty acid esters, but did not have detectable activity on long-chain water- insoluble fatty acid esters.The enzyme activity was inhibited by diisopropyl fluorophosphate and phenylsulfonyl fluoride.
- Nishizawa, Masako,Gomi, Hideyuki,Kishimoto, Fumitaka
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p. 594 - 598
(2007/10/02)
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- Asymmetric Copper-Catalyzed Cyclopropanation of Trisubstituted and Unsymmetrical cis-1,2-Disubstituted Olefins: Modified Bis-Oxazoline Ligands
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The Cu(I) complexes of new bis-oxazolines (3-7) prepared from the corresponding amino alcohols and malono-bis-imidate exhibit high enantioselectivity of up to 94 percent ee in the catalytic cyclopropanation of trisubstituted and unsymmetrical cis-1,2-disubstituted olefins.New diazoacetate reagents have also been developed giving high trans/cis ratios of up to 99:1 trans.
- Lowenthal, Richard E.,Masamune, Satoru
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p. 7373 - 7376
(2007/10/02)
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- Microbial Stereoselective Hydrolysis of (+/-)-cis,trans-Ethyl Chrysanthemate for Preparation of (+)-trans-Acid
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Microbial stereoselective hydrolysis of (+/-)-cis,trans-ethyl chrysanthemate was examined to prepare (+)-trans-chrysanthemic acid.Through the screening of over 228 strains from culture collections, 31 strains were found to have hydrolytic ability.Stereoselective hydrolysis by Arthrobacter (A.) globiformis IFO-12958 gave the optically pure (+)-trans-acid.The composition of cultivation media for production of the hydrolytic activity (the responsible esterase) was optimized.The optimum pH and temperature for hydrolysis of ethyl chrysanthemate were pH 10 and 55 deg C, respectively.Cells of A. globiformis IFO-12958 were treated with a chemical mutagen and the advantageous mutant SC-6-98-28, the hydrolytic activity of which was enhanced 2.5-fold, was isolated.
- Mitsuda, Satoshi,Komaki, Ryohei,Hirohara, Hideo,Nabeshima, Shigeyasu
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p. 2865 - 2870
(2007/10/02)
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- Deaminative Rearrangements of 1-Phenylthio- and 1-Oxy-Substituted Chrysanthemylamines
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Metalation of chrysanthemic nitrile 1 with lithium diisopropylamide followed by sulfenylation with diphenyl disulfide or oxygenation with a molybdenum peroxide complex gave chrysanthemic nitrile derivatives bearing phenylthio (3 and 4) or hydroxyl (6) substituents at C-1.These compounds provided access to the following series of 1-substituted chrysanthemylamines: 1-(phenylthio)chrysanthemylamine (5), 1-methoxychrysanthemylamine (8), 1-methoxydihydrochrysanthemylamine (10), and the N-nitrosooxazolidinone (13) derived from 1-hydroxychrysanthemylamine (11).Nitrous acid deamination of 5 and 8 and hydrolytic deamination of 13 gave acyclic alcohols (14, 17, and 18) related in structure to yomogi alcohol as major products by cleavage of the 1-3 cyclopropane ring bond.Products formed by cleavage of the 1-2 cyclopropane ring bond (15 and 24) and related in structure to santolinatriene were obtained in lesser amounts from the deamination of 5 and 13.Pinacol-type ring expansion to the isomeric cyclobutanones 19 and 20 was observed as a minor reaction pathway in the deaminations of 8 and 13.In contrast, deamination of 10 gave dihydrocyclobutanones 21 and 22 as the major isolated products.
- VanCantfort, Christopher K.,Coates, Robert M.
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p. 4331 - 4339
(2007/10/02)
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- A NOVEL SYNTHESIS OF (+/-)-TRANS-CHRYSANTHEMIC ACID
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A novel approach to (+/-) trans chrysanthemic acid, from commercially avaiable 2,5-dimethyl-3-hexyne-2,5-diol /30 percent overall yield) is described.
- Genet, J.P.,Piau, F.,Ficini, J.
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p. 3183 - 3186
(2007/10/02)
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- Selective oxidation of chrysanthemyl alcohol
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Chrysanthemyl alcohol is selectively oxidized to the corresponding aldehyde by contact with oxygen-containing gas in the presence of supported noble metal catalyst composed of platinum on carbon. The obtained aldehyde may be further converted to chrysanthemic acid by oxidation with a solid inorganic oxidizing agent such as silver oxide in excess of stoichiometric quantity, or by reaction with a catalytic amount of oxidation promoting catalyst such as silver oxide in the presence of cupric oxide and molecular oxygen.
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