GC-ECD determination of cypermethrin and its major metabolites in soil, elm bark, and litter

An analytical method has been developed for the simultaneous determination of residues of four pairs of isomers of the pyrethroid insecticide cypermethrin, and their main metabolites, cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylic acid (CCA) and 3-phenoxybenzoic acid (PBA), in elm bark, litter, and soil in the control of elm bark beetles, the vector of the Dutch elm disease. The residues of cypermethrin isomers and their metabolites were extracted with methanol under acidic conditions from elm bark, litter, and soil, cleaned up with liquid-liquid partitioning, and chromatographed by GC-ECD together after the CCA and PBA in the sample had been derivatized with α-bromo-2,3,4,5,6-pentafluorotoluene. The average recoveries of cypermethrin isomer pairs were 82 to 112% with relative standard deviations (RSDs) of 2.3 to 10% at the fortification levels of 2, 10, 100 μg/g in elm bark, 2, 15, 150 μg/g in litter, and 0.2, 2, 20 μg/g in soil. The recoveries of cypermethrin metabolites were 83 to 107% with RSDs from 2 to 12% at the fortification levels of 0.5, 5, and 10 μg/g in elm bark, and litter, and 0.1, 1, and 10 μg/g in soil.     

GC-ECD determination of cypermethrin and its major metabolites in soil, elm bark, and litter

An analytical method has been developed for the simultaneous determination of residues of four pairs of isomers of the pyrethroid insecticide cypermethrin, and their main metabolites, cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethyl-cyclopropanecarboxylic acid (CCA) and 3-phenoxybenzoic acid (PBA), in elm bark, litter, and soil in the control of elm bark beetles, the vector of the Dutch elm disease. The residues of cypermethrin isomers and their metabolites were extracted with methanol under acidic conditions from elm bark, litter, and soil, cleaned up with liquid-liquid partitioning, and chromatographed by GC-ECD together after the CCA and PBA in the sample had been derivatized with α-bromo-2,3,4,5,6-pentafluorotoluene. The average recoveries of cypermethrin isomer pairs were 82 to 112% with relative standard deviations (RSDs) of 2.3 to 10% at the fortification levels of 2, 10, 100 μg/g in elm bark, 2, 15, 150 μg/g in litter, and 0.2, 2, 20 μg/g in soil. The recoveries of cypermethrin metabolites were 83 to 107% with RSDs from 2 to 12% at the fortification levels of 0.5, 5, and 10 μg/g in elm bark, and litter, and 0.1, 1, and 10 μg/g in soil. Received: 8 April 1997 / Revised: 21 July 1997 / Accepted: 23 July 1997     

Liquid chromatography of jasmonic acid amine conjugates

Summary Racemic jasmonic acid (3R,7R/3S,7S)-(±)-JA) was chemically conjugated with different biogenic amines originating from aliphatic and aromatic α-amino acids by decarboxylation. The resulting isomeric compounds were subjected to reversed-phase high-performance liquid chromatography (HPLC) and to HPLC on the chiral stationary phases Chiralpak AS and Nucleodex β-PM. Under reversed-phase conditions, all the homologous amine derivatives tested could be separated from each other except the JA-conjugates containing 2-phenyl-ethylamine and 3-methylbutylamine. On both chiral supports the (3R,7R)-(−)-JA conjugates eluted earlier than those of the enantiomeric counterpart (3S,7S)-(+)-JA. On Chiralpak AS all the isomers studied could be separated to baseline with a mobile phase containingn-hexane and 2-propanol. The calculated resolution factors were between 1.80 and 4.17. The pairs of isomers were also chromatographed on the cyclodextrin stationary phase Nucleodex β-PM with methanol-triethylammonium acetate buffer as mobile phase. Under these conditions resolution factors were between 0.74 and 1.29. The individual isomers were chiroptically characterized by measurement of their circular dichroism.     

Diastereoselective and enantioselective chromatography of the pyrethroid insecticides allethrin and cypermethrin

Summary Liquid and gas chromatographic separations of the pyrethroid insecticides allethrin and cypermethrin have been investigated with various achiral and chiral stationary phases. Diastercomeric and enantiomeric selectivity was observed for cypermethrin on a Pirkle-type chiral LC stationary phase, but very strong interactions and therefore long retention times prevented the separation of allethrin on this phase. Trans-allethrin isomers were separated on a chiral -cyclodextrin RP-HPLC column while cypermethrin showed some difficulties on this phase due to isomerization. Diastereomeric but no enantiomeric selectivity by GC was achieved for cypermethrin with an apolar DB 5 capillary. GC separation of the diastereomers was used to study the selective photodegradation of cypermethrin isomers after forestry applications. Chiral -cyclodextrin-based GC phases showed some enantioselectivity for cis- and trans-allethrin isomers. A separation of the eight isomers into six partially resolved peaks was achieved by GC with a coupled column consisting of chiral permethylated -cyclodextrin and DB 1701 as stationary phases. This combination was used to characterize allethrin formulations intended for indoor use and to investigate allethrin products formed by ozonolysis of thin films of the insecticide.     

Enantioselective analysis of venlafaxine and its active metabolites: A review on the separation methodologies

Venlafaxine (VFX) is a serotonin and norepinephrine reuptake inhibitor chiral drug used in therapy as an antidepressant in the form of a racemate consisting of R‐ and S‐VFX. The two enantiomers of VFX exhibit different pharmacological activities: R‐VFX inhibits both norepinephrine and serotonin synaptic reuptake, whereas S‐VFX inhibits only the serotonin one. R‐ and S‐VFX are metabolized in the liver to the respective R‐ and S‐O‐desmethylvenlafaxine (ODVFX), R‐ and S‐N‐desmethylvenlafaxine (NDVFX), and R‐ and S‐N,O‐didesmethylvenlafaxine (NODVFX). The pharmacological profile of ODVFX is close to that of VFX, whereas the other two chiral metabolites (NDVFX and NODVFX) have lower affinity for the receptor sites. The pharmacokinetics of the VFX enantiomers appear stereoselective, including the metabolism process. In the past 20 years, several studies describing the enantioselective analysis of R‐ and S‐VFX in pharmaceutical formulations and its chiral metabolites in biological matrices were published. These methods encompass liquid chromatography coupled with UV detection, mass spectrometry, or tandem mass spectrometry, and capillary electrophoresis. This paper reviews the published methods used for the determination of the individual enantiomers of VFX and its chiral metabolites in different matrices.     

Enzymatic resolution of α-hydroxyphosphinates with two stereogenic centres and determination of absolute configuration of stereoisomers obtained

The use of quinine as a chiral solvating agent allows us to determine a tentative absolute configuration at the phosphorus atom of hydroxyphosphinates with two stereogenic centres (at the phosphorus and α-carbon atoms). Two ethyl butyryloxyalkane(P-phenyl)phosphinates were hydrolysed using various lipases. In all cases isomers possessing α-carbon atom with an (S)-configuration were hydrolysed preferentially. The absolute configuration of both chiral centres of obtained α-hydroxyphosphinates was determined by using (S)-(+)-MTPA-Cl and quinine. The mode of chiral discrimination of α-hydroxyphosphinates by quinine was studied by means of computational chemistry, which confirmed the experimental findings that the signals in ³¹P NMR spectra of compounds with an (R_P)-configuration are situated upfield when compared with the respective (S_P) isomers.     

1H NMR discrimination of CHF4226.01 diastereoisomers in DMSO‐d6

Two diastereoisomers CHF4226.01 (R, R) and CHF4232.01 (S, R), differing for a chiral center, have been studied to investigate their possible discrimination using NMR. 1D NMR and 2D NMR experiments, such as COSY, NOESY and ROESY, were performed on pure isomers and on the association complexes formed in the presence of the chiral reagent (S)‐(?)‐1‐(2‐napthyl)ethylamine (S‐NEA). Moreover, computational studies, concerning conformational analysis and molecular dynamics, were started and supported the NMR results. Copyright © 2009 John Wiley & Sons, Ltd.     

Enantiomeric high‐performance liquid chromatography resolution and absolute configuration of 6β‐benzoyloxy‐3α‐tropanol

The absolute configuration of the naturally occurring isomers of 6β‐benzoyloxy‐3α‐tropanol ( 1 ) has been established by the combined use of chiral high‐performance liquid chromatography with electronic circular dichroism detection and optical rotation detection. For this purpose (±)‐ 1 , prepared in two steps from racemic 6‐hydroxytropinone ( 4 ), was subjected to chiral high‐performance liquid chromatography with electronic circular dichroism and optical rotation detection allowing the online measurement of both chiroptical properties for each enantiomer, which in turn were compared with the corresponding values obtained from density functional theory calculations. In an independent approach, preparative high‐performance liquid chromatography separation using an automatic fraction collector, yielded an enantiopure sample of _OR(+)‐ 1 whose vibrational circular dichroism spectrum allowed its absolute configuration assignment when the bands in the 1100–950 cm^‐1 region were compared with those of the enantiomers of esters derived from 3α,6β‐tropanediol. In addition, an enantiomerically enriched sample of 4 , instead of _OR(±)‐ 4 , was used for the same transformation sequence, whose high‐performance liquid chromatography follow‐up allowed their spectroscopic correlation. All evidences lead to the _OR(+)‐(1S,3R,5S,6R) and _OR(?)‐(1R,3S,5R,6S) absolute configurations, from where it follows that samples of 1 isolated from Knightia strobilina and Erythroxylum zambesiacum have the _OR(+)‐(1S,3R,5S,6R) absolute configuration, while the sample obtained from E. rotundifolium has the _OR(?)‐(1R,3S,5R,6S) absolute configuration.     

一种含有手性联萘“铰链”单元的环芳分子的设计、合成及表征

基于联萘衍生物手性构型高度稳定以及联萘结构中2个萘平面的两面角可以在一定范围内张合的特点, 分别以光学活性的(R)和(S)-2,2'-二乙炔基-1,1'-联萘为模板, 设计了一种含有8个“铰链”结构单元的新的环芳分子¾—(R,R,R,R,R,R,R,R)-3和(S,S,S,S,S,S,S,S)-3. 其合成路线涉及间苯基连接桥的链接, 保护基的脱去和控制导入以及分子间偶合等步骤. 用MS, IR, UV-Vis, ¹H和¹³C NMR以及元素分析等技术对中间体和目标化合物进行了结构表征. 测定并比较了2个目标化合物的比旋光度[α]_D和圆二色(CD)性质. 在CH₂Cl₂溶液中, 两个异构体(R,R,R,R,R,R,R,R)-3和(S,S,S,S,S,S,S,S)-3的[α]_D²⁵值分别为－911.8和＋908.6, 并且它们的CD谱表现出对称的镜像特征．这些实验结果清楚地反映了它们之间的对映异构关系.     

Analytical and semipreparative separation of 25 (R/S)‐spirostanol saponin diastereomers using supercritical fluid chromatography

Spirostanol saponins are a class of steroidal saponins with many pharmacological activities. The structural complexity of the spirostanol saponins presents a daunting challenge in separating their 25 R/S diastereomers. Using two CHIRALPAK IC columns coupled in series, six 25 (R/S)‐spirostanol saponin diastereomers from the Trigonella foenum‐graecum L. seed were successfully separated using supercritical fluid chromatography (SFC) for the first time. In addition, three 25 (R/S)‐spirostanol saponin diastereomers were isolated into their respective individual isomers. The structures of the isolated isomers were unambiguously confirmed by NMR analysis. The SFC method development strategy and its associated underlying principles presented in this paper are generally applicable. SFC is a viable addition to the natural product research toolbox, especially for stereoselective analysis and purification.     

Enantioselective Syntheses of Lignin Models: An Efficient Synthesis of β‐O‐4 Dimers and Trimers by Using the Evans Chiral Auxiliary

We describe an efficient five‐step, enantioselective synthesis of (R,R)‐ and (S,S)‐lignin dimer models possessing a β‐O‐4 linkage, by using the Evans chiral aldol reaction as a key step. Mitsunobu inversion of the (R,R)‐ or (S,S)‐isomers generates the corresponding (R,S)‐ and (S,R)‐diastereomers. We further extend this approach to the enantioselective synthesis of a lignin trimer model. These lignin models are synthesized with excellent ee (>99 %) and high overall yields. The lignin dimer models can be scaled up to provide multigram quantities that are not attainable by using previous methodologies. These lignin models will be useful in degradation studies probing the selectivity of enzymatic, microbial, and chemical processes that deconstruct lignin.     

Efficient Synthesis of Enantiomerically Pure α-Ionone from (R)- and (S)-α-Damascone

(R)- and (S)-α-ionone ((R)- and (S)- 1 , resp.) were prepared from (R)- and (S)-α-damascone ((R)- and (S)- 3 , resp.) without racemization in 48% yield employing a new enone transposition. The described transposition is complementary to existing methods whose application is often prohibited by the structural requirements of the substrate. The now easily accessible α-ionones of desired absolute configuration are useful as chiral building blocks for terpenoid synthesis.     

Recent advances of optically active helical polymers as adsorbents and chiral stationary phases for chiral resolution

Chiral resolution is very important and still a big challenge due to different biological activity and same physicochemical property of one pair (R)- and (S)-isomer. There is no doubt that chiral selectors are essentially needed for chiral resolution, which can stereoselectively interact with a pair of isomers. To date, a large amount of optically active helical polymers as chiral selectors have been synthesized via two strategies. First, the target helical polymers are derived from natural polysaccharide such as cellulose and amylose. Second, they can be synthesized by polymerization of chiral monomers. Alternatively, an achiral polymer is prepared first followed by static or dynamic chiral induction. Furthermore, a part of them is harnessed as chiral stationary phases for chromatographic chiral separation and as chiral adsorbents for enantioselective adsorption/crystallization, resulting in good enantioseparation efficiency. In summary, the present review will focus on recent progress of the polymers with optical activity for chiral resolution, especially the literature published in the past 10 years. In addition, development prospects and future challenges of optically active helical polymers will be discussed in detail.     

Totalsynthese von natürlichem α-Tocopherol 3. Mitteilung. Aufbau der Seitenkette mit (−)-(S)-2-Methyl-γ-butyrolacton als zentralem Baustein

Total Synthesis of Natural α-Tocopherol (?)-(S)-2-Methyl-γ-butyrolactone ( 2 ) represents a versatile chiral C₅-synthon. It serves as key intermediate in one of the syntheses of certain isoprenoid derivatives such as (R)-dihydrocitronellol, (3R, 7R)-hexahydrofarnesol and vitamin E of natural configurations. Their syntheses are described in detail.     

Enantioselective HPLC analysis of escitalopram oxalate and its impurities using a cellulose-based chiral stationary phase under normal- and green reversed-phase conditions

Normal-phase and reversed-phase high-performance liquid chromatography methods for the separation of the active pharmaceutical ingredient escitalopram from its (R)-enantiomer impurity have been developed on the cellulose-based Chiralcel OJ-H chiral stationary phase. Both methods share two features: they use ethanol as a cosolvent and are able to give a complete enantioseparation without interference from other associated chiral impurities. With the green eluent mixture ethanol–water–diethylammine 70:30:0.1 (v/v/v), the resolution between escitalopram and (R)-enantiomer was 2.09 at 30°C. The limits of quantification for the (S) and (R) enantiomers were 4.5 and 3.8 μg mL⁻¹, respectively.     

α-Alkylation of Amino Acids without Racemization. Preparation of Either (S)- or (R)-α-Methyldopa from (S)-Alanine

Enantiomerically pure cis- and trans-5-alkyl-1-benzoyl-2-(tert-butyl)-3-methylimidazolidin-4-ones ( 1, 2, 11, 15, 16 ) and trans-2-(tert-butyl)-3-methyl-5-phenylimidazolidin-4-one ( 20 ), readily available from (S)-alanine, (S)-valine, (S)-methionine, and (R)-phenylglycine are deprotonated to chiral enolates (cf. 3, 4, 12, 21 ). Diastereoselective alkylation of these enolates to 5,5-dialkyl- or 5-alkyl-5-arylimidazolidinones ( 5, 6, 9, 10, 13a-d, 17, 18, 22 ) and hydrolysis give α-alkyl-α-amino acids such as (R)- and (S)-α-methyldopa ( 7 and 8a , resp.), (S)-α-methylvaline ( 14 ), and (R)-α-methyl-methionine ( 19 ). The configuration of the products is proved by chemical correlation and by NOE ¹H-NMR measurements (see 23, 24 ). In the overall process, a simple, enantiomerically pure α-amino acid can be α-alkylated with retention or with inversion of configuration through pivaladehyde acetal derivatives. Since no chiral auxiliary is required, the process is coined ‘self-reproduction of a center of chirality’. The method is compared with other α-alkylations of amino acids occurring without racemization. The importance of enantiomerically pure, α-branched α-amino acids as synthetic intermediates and for the preparation of biologically active compounds is discussed.     

Enzymes in organic chemistry. Part 10: Chemo-enzymatic synthesis of l-phosphaserine and l-phosphaisoserine and enantioseparation of amino-hydroxyethylphosphonic acids by non-aqueous capillary electrophoresis with quinine carbamate as chiral ion pair agent

Diisopropyl 2-azido-1-acetoxyethylphosphonate (±)-7 was hydrolysed with high enantioselectivity by lipase SP 524 to give α-hydroxyphosphonate (S)-(−)-6 and ester (R)-(−)-7, which was saponified to give (R)-(+)-6. The two α-hydroxyphosphonates (R)- and (S)-6 were transformed into l-phosphaisoserine and l-phosphaserine, respectively. Their enantiomeric excesses were determined to be 97% by HPLC on an chiral stationary phase. A mixture of all four stereoisomeric amino-hydroxyethylphosphonic acids can be separated by non-aqueous capillary electrophoresis with quinine carbamate as the chiral ion pair agent applying the partial filling technique.     

A novel approach for LC-MS/MS-based chiral metabolomics fingerprinting and chiral metabolomics extraction using a pair of enantiomers of chiral derivatization reagents

Chiral metabolites are found in a wide variety of living organisms and some of them are understood to be physiologically active compounds and biomarkers. However, the overall analysis of chiral metabolomics is quite difficult due to the high number of metabolites, the significant diversity in their physicochemical properties, and concentration range from metabolite-to-metabolite. To solve this difficulty, we developed a novel approach for chiral metabolomics fingerprinting and chiral metabolomics extraction, which is based on the labeling of a pair of enantiomers of chiral derivatization reagents (i.e., DMT-(S,R)-Pro-OSu and DMT-3(S,R)-Apy) and precursor ion scan chromatography of the derivatives. The multivariate statistics is also required for this strategy. The proposed procedures were evaluated by the detection of a diagnostic marker (i.e., d-lactic acid) using the saliva of diabetic patients. This method was used for the determination of biomarker candidates of chiral amines and carboxyls in Alzheimer's disease (AD) brain homogenates. As the results, l-phenylalanine (L-Phe) and l-lactic acid (L-LA) were identified as the decreased and increased biomarker candidates in the AD brain, respectively. Therefore, the proposed approach seems to be helpful for the determination of non-target chiral metabolomics possessing amines and carboxyls.     

Determination of pyrethroid metabolites in human urine by capillary gas chromatography-mass spectrometry

Summary An analytical method for the simultaneous determination of the pyrethroid metabolites cis and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, cis 3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane carboxylic acid, 3-phenoxybenzoic acid and 4-fluoro-3-phenoxybenzoic acid in human urine samples is described. The urine is subjected to acid-induced hydrolysis followed by exhaustive solvent extraction, covering both conjugated and free acids, followed by a common derivatisation step yielding the corresponding methyl esters. Quantitation was by diastereomeric, capillary gas chromatography-mass spectrometry. It appears that 4-fluoro-3-phenoxybenzoic acid is a characteristic urinary marker for cyfluthrin exposure. The limits of determination are 0.5–1.0 g L^–1 urine depending on the metabolites concerned. The applicability of the method was tested on urine samples from pest control operators exposed occupationally to cypermethrin and cyfluthrin.     

Design,enantioselective synthesis,and antiviral activities against potato virus Y of axially chiral thiazine derivatives

A series of novel thiazine derivatives featuring axial chirality in both (R) and (S) configurations were successfully synthesized by N-heterocyclic carbene (NHC)-catalyzed enantioselective [3 + 3] annulations, and their potential as anti-plant virus agents against potato virus Y (PVY) was evaluated. Biological activity results demonstrated that most of these chiral thiazine derivatives exhibited significant activities against PVY. Notably, compound (S) -3g displayed a remarkable 58% inactivation effect against PVY at a concentration of 500 μg/mL, slightly surpassing the effectiveness of Ningnanmycin (NNM) at 57%. Additionally, (S) -3g exhibited curative activity of 57%, which is superior to NNM (53%). Molecular docking studies revealed preliminary insights into the distinct biological properties of the two different enantiomers, (R) or (S) -3g against PVY, wherein single enantiomer (S) -3g formed a more stable interaction with PVY-CP, as indicated by its lower binding free energy (−41.18 kcal/mol) compared to (R)- 3g (−36.9 kcal/mol). The findings in this study with a new class of axially chiral thiazine derivatives shall inspire further development of chiral heterocycles as potential drug candidates for the protection of plant virus infections.