Enantiomeric impurities in chiral catalysts,auxiliaries, and synthons used in enantioselective syntheses. Part 5

The enantiomeric excess of chiral starting materials is one of the important factors determining the enantiopurity of products in asymmetric synthesis. Fifty‐one commercially available chiral reagents used as building blocks, catalysts, and auxiliaries in various enantioselective syntheses were assayed for their enantiomeric purity. The test results were classified within five impurities level (ie, <0.01%, 0.01%‐0.1%, 0.1%‐1%, 1%‐10%, >10%). Previously from 1998 to 2013, several reports have been published on the enantiomeric composition of more than 300 chiral reagents. This series of papers is necessitated by the fact that new reagents are forthcoming and that the enantiomeric purity of the same reagent can vary from batch to batch and/or from supplier to supplier. This report presents chiral liquid chromatography (LC) and gas chromatography (GC) methods to separate enantiomers of chiral compounds and evaluate their enantiomeric purities. The accurate and efficient LC analysis was done using newly introduced superficially porous particle (SPP 2.7 μm) based chiral stationary phases (TeicoShell, VancoShell, LarihcShell‐P, and NicoShell).     

Mass balancing in kinetic resolution: calculating yield and enantiomeric excess using chiral balance

When kinetic resolution is applied for the production of enantiomerically pure compounds, process options may be used which involve more than one chiral substrate and one chiral product, such as sequential or parallel enzymatic kinetic resolutions or hydrolysis of diastereomers. Although the relation between the yields (y) of the chiral compounds is straightforward in these cases, the relation between their enantiomeric excess (ee) values is not. Combining mass balances into a so-called chiral balance (Sigma y . ee(R) = 0) provides the relation between enantiomeric excess values in a useful manner. This chiral balance easily shows which nonmeasured enantiomeric excess values and yields can be calculated from measured values. The chiral balance is only valid when configurations at chiral centers are conserved. (c) 1995 John Wiley & Sons, Inc.     

Alcohol Induced Reversal of Enantioselectivity in a Lipase Catalyzed Resolution of 2-Chloropropionic Acid

Alcohol induced reversal of enantioselectivity in the esterification of 2-chloropropionic acid using lipase from Candida cylindracea has been investigated. It was found that an alcohol having substituents both at the α- and the β-carbon preferentially esterified the S-acid, while a straight chain alcohol preferentially esterified the R-acid. Intermediate enantioselectivities were obtained with alcohols having substituents either at the α- or the β-carbon, but still in favor of the R-acid. An acyl binding domain composed of three subsites is proposed for this lipase; one for the hydrocarbon chain, a second for a methyl substituent and a third for an electronegative substituent.     

Conversion of a racemate into a single enantiomer in one step by chiral liquid chromatography: Studies with rac-2,2′-diiodobiphenyl

The enantiomers of rac-2,2′-diiodobiphenyl were separated by liquid chromatography on microcrystalline triacetylcellulose. The conformational lability, a large separation factor α, and a suitable capacity factor k′(+) of this biphenyl allowed us to convert the racemate into 90% of enantiomerically pure (-)-2,2′-diiodobiphenyl and 10% of pure (+)-2,2′-diiodobiphenyl, respectively, by a series of in situ racemization-elution cycles. The much better retained (+)-enantiomer was racemized on the chromatographic column at 50°C after the less retained (-)-enantiomer has already been eluted at 8°C. © 1995 Wiley-Liss, Inc.     

Molecular tweezers for enantiodiscrimination in NMR: Di‐(R,R)‐1‐[10‐(1‐hydroxy‐2,2,2‐trifluoroethyl)‐9‐anthryl]‐2,2,2‐trifluoroethyl benzenedicarboxylates

A series of new chiral molecular tweezers, di‐(R,R)‐1‐[10‐(1‐hydroxy‐2,2,2‐trifluoroethyl)‐9‐anthryl]‐2,2,2‐trifluoroethyl phthalate (2), isophthalate (3) and terephthalate (4), were synthesized and their structure studied by NMR and molecular mechanics. Their effectiveness as chiral solvating agents for the determination of the enantiomeric purity of chiral compounds using NMR was demonstrated. Chirality 2010. © 2009 Wiley‐Liss, Inc.     

Cytotoxic fungal spores in the indoor atmosphere of the damp domestic environment

Eight-three fungal isolates collected and cultured from the air spora of damp public sector Scottish housing have been screened for cytotoxic properties. A bioassay procedure has been utilised for this purpose involving cytotoxic effects on human embryonic diploid fibroblast lung cells grown as monolayer cultures within the wells of microtitre plates. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] biochemical assay system employed has revealed that 39 (47%) of the moulds investigated possessed spore-associated cytotoxic properties; a value which emphasises the potential health hazards of the continual inhalation of toxigenic fungal propagules by occupants of mouldy houses. Penicillia, the most prevalent fungi found in the internal atmosphere of the domestic environment, accounted for the great majority of cytotoxic strains identified.     

A rapid analytical method for monitoring the enantiomeric purity of chiral molecules synthesized in ionic liquid solvents

Ionic liquids (ILs) have been widely used as reaction solvents in asymmetric synthesis due to their interesting physical and chemical properties. However, monitoring reactant-to-product conversion and the enantiopurity of formed stereoisomers often involves a tedious extraction step before chromatographic analysis. In this study, a rapid and sensitive sampling method using headspace solid-phase microextraction (SPME) coupled to chiral gas chromatography was developed for the "on-line" analysis of chiral molecules in the IL solvent. Three different SPME sorbent coatings, namely polydimethylsiloxane, polyacrylate, and a polymeric ionic liquid-based fiber, were examined in this study. The analytical performance of the developed method was evaluated in terms of reproducibility, slope of calibration curve, linear range, calibration linearity, and the determination of detection limits. The SPME method was successfully applied in the determination of enantiomeric excess from selected mixtures of chiral molecules. A preliminary study was performed using an "on-fiber" derivatization approach revealing that the stereoisomers extracted by the SPME fiber can be efficiently derivatized using a short "on-fiber" derivatization step. The developed SPME method eliminates the need of sequestering the reaction, separating the compounds of interest from the IL solvent, and the addition of a derivatizing reagent.     

家养食草动物粪便中的花粉及菌孢子类型及其对人类活动的指示意义

考古遗址中动物粪化石中的微体植物遗存是重建过去生态环境以及人类活动的重要材料,然而对于能够指示人类活动的粪化石孢粉组合类型及其特征仍然缺乏清楚的认识。本文研究了山羊(Capra aegagrus)、绵羊(Ovis aries)、牛(Bos taurus)、骆驼(Camelus)、牦牛(Bos grunniens)和马(Equus caballus)等几种中国常见的家养食草类动物粪便中的主要孢粉和真菌孢子类型。通过分析这些动物粪便的花粉组合特征,探讨了花粉和菌孢子等微体植物遗存对生态环境及人类活动的指示意义。花粉种类丰度低、一些特征种属花粉(如禾本科、藜科)含量高是家养食草类动物粪便花粉组合的主要特征,可以用于指示人类的饲养行为。家养食草动物粪便中的粪生真菌孢子类型主要有Sporormiella,Sodaria,Pleospora,Coniochaeta,Thecaphora and Dictyosporium。研究表明真菌孢子的分布主要受到动物活动范围的影响,这使得利用粪生菌孢子(如Sporormiella)并结合其他记录来反映人类的饲养或游牧活动成为可能。     

Synthesis and in vitro sodium channel blocking activity evaluation of novel homochiral mexiletine analogs

New chiral mexiletine analogs were synthesized in their optically active forms and evaluated in vitro as use‐dependent blockers of skeletal muscle sodium channels. Tests carried out on sodium currents of single muscle fibers of Rana esculenta demonstrated that all of them exerted a higher use‐dependent block than mexiletine. The most potent analog, (S)‐3‐(2,6‐dimethylphenoxy)‐1‐phenylpropan‐1‐amine (S)‐( 5 ), was six‐fold more potent than (R)‐Mex in producing a tonic block. As observed with mexiletine, the newly synthesized compounds exhibit modest enantioselective behavior, that is more evident in 3‐(2,6‐dimethylphenoxy)butan‐1‐amine ( 3 ). Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Circular dichroism detection in HPLC

A circular dichroism-based detection system presents several advantages in the HPLC analysis of chiral compounds because of the selective monitoring of optically active molecules. Its use allows reliable determination of enantiomeric excesses and elution order. To this end, the application of empirical, semiempirical, and nonempirical methods to get stereochemical information from the CD signal is reported. Furthermore, recording the CD spectra on line and evaluation of the dissymetry factor make the CD detection very powerful in characterizing the stereochemistry of chiral eluates.     

The effect of sodium chlorate and nitrapyrin on the nitrification mediated nitrosation process in soils

Summary The influence of total nitrification to nitrate or partial nitrification to nitrite on the soil organic nitrogen status was examined. NH ₄ ⁺ –¹⁵N was added to the soil in the absence and the presence of NaClO₃, respectively nitrapyrin. The first chemical inhibits only nitrate formation, the second inhibits total nitrification. The accumulation of nitrite nitrogen in the soil at levels up to 5 mg kg^–1 increased the loss of nitrogen. Yet, it did not increase the binding of mineral nitrogen into soil organic matter, relative to the control soil. The data suggest that the biochemistry of the nitrite formation process, rather than the levels of nitrite ions formed, are of primary importance in the role of nitrification mediated nitrosation of soil organic matter.     

Spatial variability of arbuscular mycorrhizal fungal spores in two natural plant communities

Geostatistical techniques were used to assess the spatial patterns of spores of arbuscular mycorrhizal fungi (AMF) in soils from two contrasting plant communities: a salt marsh containing only arbuscular mycorrhizal and non-mycorrhizal plants in a distinct clumped distribution pattern and a maquis with different types of mycorrhiza where most plants were relatively randomly distributed. Also evaluated was the relationship between the spatial distribution of spores and AM plant distribution and soil properties. A nested sampling scheme was applied in both sites with sample cores taken from nested grids. Spores of AMF and soil characteristics (organic matter and moisture) were quantified in each core, and core sample location was related to plant location. Semivariograms for spore density indicated strong spatial autocorrelation and a patchy distribution within both sites for all AM fungal genera found. However, the patch size differed between the two plant communities and AM fungal genera. In the salt marsh, AM fungal spore distribution was correlated with distance to AM plants and projected stand area of AM plants. In maquis, spatial AM fungal spore distribution was correlated with organic matter. These results suggest that spore distribution of AMF varied between the two plant communities according to plant distribution and soil properties.     

Seasonal variation of fungal propagules in a fruit market environment, Nagpur (India)

The concentration of airborne fungal spores in a marketenvironment was examined to provide basic information needed to evaluatethe importance of varying levels and heterogeneity. Sampling has beencarried out by rotorod sampler and exposed Petri plate method to obtainthe quantitative and qualitative estimations respectively.Aspergillus was the most frequent and predominant genusdetected. Cladosporium, Penicillium and Alternariaspores were also fairly abundant which are well known as allergenic andpathogenic. The high concentration of airborne spores was recordedduring December–January. While the maximum concentration ofAspergillus was found during summer months in the marketenvironment.     

2-C-Methyl-d-erythritol. Produced in plants,forms aerosols in the atmosphere. An alternative pathway in isoprenoid biosynthesis

2-C-Methyltetritols, or 2-methyl-1,2,3,4-butanetetraols, which exist as four stereoisomers, are found to be present in the atmosphere above the Amazonian rainforest. 2-C-methyl-d-erythritol was originally isolated from Convolvulus glomeratus and later synthesized enantiomerically pure. It has been claimed that these compounds are produced from isoprene by radical oxidation in the atmosphere. More recently, detailed analysis has shown that the mixture of stereoisomers from forests in both Brazil and Sweden contains unequal amounts of enantiomers. This shows that the oxidation must be due to enzymatic activity in plants. A review of the history of these compounds, synthesis and the significance of stereochemistry is given. Moreover, the significance of 2-C-methyl-d-erythritol for the non-mevalonate route to isoprenoids is briefly discussed.