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A method for the highly regioselective reductive coupling reaction of N-aryl-α-imino esters with dienes is described. The method utilizes the RuHCl(CO)(PPh3)3/iPrOH catalytic system under an Ar atmosphere and provides α-branched allylic α-amino acid derivatives. Application of this transformation to the concise synthesis of a natural plant growth regulator is demonstrated. [ABSTRACT FROM AUTHOR]

A novel cascade cyclization of ethyl glyoxalate and amines proceeds in the presence of Pd(TFA)2(5 mol %) to give the cyclic dehydro-α-amino acid derivatives. This method provides a fast and simple access to highly substituted dihydro-pyrrol-2-ones in good yields. [ABSTRACT FROM AUTHOR]

Our recent investigation on the insecticidal activities of several doramectin derivatives preliminarily revealed that the presence of hydrogen bonds at the C4″ position of the molecule with target protein γ-aminobutyric acid (GABA) receptor was crucial for retaining high insecticidal activity. As a continuation of our research work on the development of new insecticides, two series of novel acylurea and acylthiourea doramectin derivatives were designed and synthesized. The bioassay results indicated that the newly synthesized compounds ( 5o , 5t , and 6t ) exhibited higher insecticidal activity against diamondback moth, oriental armyworm, and corn borer than the control compounds doramectin, commercial avermectins, chlorbenzuron, and lead compound 3g in our laboratory. Specifically, compound 5t was identified as the most promising insecticide against diamondback moth, with a final mortality rate of 80.00% at the low concentration of 12.50 mg/L, showing approximately 7.75-fold higher potency than the parent doramectin (LC 50 value of 48.1547 mg/L), 6.52-fold higher potency than commercial avermectins (LC 50 value of 40.5507 mg/L), and 3.98-fold higher potency than compound 3g (LC 50 value of 24.7742 mg/L). Additionally, molecular docking simulations revealed that compound 5t (2.17, 2.20, 2.56, and 2.83 Å) displayed stronger hydrogen-bond action in binding with the GABA receptor, better than that of compound 5o (1.64 and 2.15 Å) and compound 6t (2.20 and 2.31 Å) at the C4″ position. This work demonstrated that these compounds containing hydrogen-bond groups might contribute to the improvement of insecticidal activity and supply certain hints toward structure optimization design for the development of new insecticides.

A cobalt(II)-catalyzed regioselective aryl C-H bond oxygenation between arenes and aryl or aliphatic carboxylic acids under bidendate-chelation assistance is developed. This method provides an efficient approach to acyoxy-substituted arenes with a broad range of functional group tolerance. Furthermore, this reaction system could be further applied to the preparation of polyfunctional naphthylenes.

A novel Pd(II)-catalyzed pyridine N-oxide directed remote arylation of unactivated Csp(3)-H bonds in aliphatic amides with aryl iodides has been developed. This protocol allows installing various aryl groups at the β- or γ-Csp(3) atom of alkyl carboxylic acid amides. The key palladabicyclic intermediate of this transformation has been identified by HR-MS and (1)H NMR method.

A Pd-catalyzed cascade oxidation/sp(2) C-H bond acylation of azoarenes was developed in which readily available aryl methanes were used as the in situ generated acyl sources. This reaction provides a convenient access to ortho-acyl azoarenes under mild conditions.

6:2 FTOH and 8:2 FTOH [FTOHs, F(CF2)nCH2CH2OH, n = 6, 8] are the principal polyfluorinated raw materials used to manufacture FTOH-based products, which may be released to WWTPs during their product life cycle. For the first time, anaerobic biotransformation of FTOHs and key biotransformation intermediates in WWTP digester sludge under methanogenic conditions was investigated. 6:2 FTOH was transformed to 6:2 FTCA, [F(CF2)6CH2COOH, 32-43 mol %], 6:2 FTUCA [F(CF2)5CF═CHCOOH, 1.8-8.0 mol %], and 5:3 acid [F(CF2)5CH2CH2COOH, 18-23 mol %] by day 90 and day 176 in two separate studies. 8:2 FTOH was transformed by day 181 to 8:2 FTCA (18 mol %), 8:2 FTUCA (5.1 mol %), and 7:3 acid (27 mol %). 6:2 and 8:2 FTOH anaerobic biotransformation led to low levels of perfluorohexanoic acid (PFHxA, ≤0.4 mol %) and perfluorooctanoic acid (PFOA, 0.3 mol %), respectively. 6:2 FTUCA anaerobic biotransformation led to a newly identified novel transient intermediate 3-fluoro 5:3 acid [F(CF2)5CFHCH2COOH] and 5:3 acid, but not 5:2 sFTOH [F(CF2)5CH(OH)CH3] and α-OH 5:3 acid [F(CF2)5CH2CH(OH)COOH], two precursors leading to PFPeA (perfluoropentanoic acid) and PFHxA. Thus, FTOH anaerobic biotransformation pathways operated by microbes in the environment was likely inefficient at shortening carbon chains of FTOHs to form PFCAs (perfluorinated carboxylic acids). These results imply that anaerobic biotransformation of FTOH-based products may produce polyfluorinated acids, but is not likely a major source of PFCAs detected in anaerobic environmental matrices such as anaerobic digester sludge, landfill leachate, and anaerobic sediment under methanogenic conditions.

A protocol for Pd(II)-catalyzed asymmetric arylation of N-aryl imino esters has been developed. The method affords a practical and direct access to chiral arylglycine derivatives in good yields and with high enantioselectivities.

This paper provides the results of an investigation on dietary intakes and internal doses of polycyclic aromatic hydrocarbons (PAHs) for nonsmoking women from Beijing, China. Concentrations of PAHs were measured by gas chromatography/mass spectrometry (GC/MS) for human milk, placenta, and umbilical cord blood samples from 40 nonsmoking women and for 144 composite food samples covering major food categories. Information on food consumption and estimated ingestion doses of PAHs by the cohort was also collected individually. Relationship among the studied human samples and relative importance of breastfeeding to the total exposure dose of infants were addressed. The median (mean and standard deviation) total concentrations of 15 PAHs in human milk, placenta, and umbilical cord blood with (or without) fat normalization were 278 (9.30 ± 5.75), 819 (35.9 ± 15.4), and 1370 (5.521 ± 3.71) ng/g of fat, respectively, and the corresponding levels of benzo[a]pyrene equivalent (B[a]P(equiv)) were 11.2 (0.473 ± 0.605), 16.2 (0.717 ± 0.318), and 13.1 (0.140 ± 0.225) ng/g of fat, respectively. The calculated intake of B[a]P(equiv) by Beijing cohort varied from 0.609 to 4.69 ng·kg(-1)·day(-1) with a median value of 1.93 (2.09 ± 0.921 mean ± standard deviation) ng·kg(-1)·day(-1). Significant correlations were found among human milk, placenta, and umbilical cord blood (p < 0.05) for low-molecular-weight PAHs, indicating selective transfer potential of individual PAHs from mother to fetus. Internal dose of PAHs was not in proportion to amounts of food ingestion, daily dietary intake, lifestyle, and social-demographic characteristics of the participants (p > 0.05). Ingested doses of PAHs (3.00-102 ng·kg(-1)·day(-1)), which were much higher than the inhaled doses (0.152-8.50 ng·kg(-1)·day(-1)), were 3-4 orders of magnitude lower than the recommended reference doses, unlikely to impose any obvious risk based on current knowledge.

To identify the ligands for σ(1) receptors that are potent and selective, analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues synthesized and tested, 5 displayed very high affinity for σ(1) (K(i) = 0.48-4.05 nM) and high selectivity for σ(1) relative to σ(2) receptors (σ(1)/σ(2) selectivity of >749-fold). Four of the five compounds (14a, 14b, 14c, and 14e) showed very low affinity for VAChT (K(i) > 290 nM), and the fifth compound (14g) showed moderate affinity for VAChT (K(i) = 44.2 nM). The compound [1'-(4-fluorobenzyl)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4-fluorophenyl)methanone (14a) displayed very high affinity and selectivity for σ(1) receptor (K(i) = 0.48 nM, σ(1)/σ(2) > 3600). All four of these most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with fluorine-18 or carbon-11, which will allow further evaluation of their properties as PET probes for imaging σ(1) receptor in vivo.

A previous study on mobilization of organochlorine pesticides (OCPs) in contaminated soils from the field revealed that the total amount of OCPs measured in digestive fluid and chyme of an in vitro gastrointestinal model was higher than the quantity directly extracted using a solvent extraction without digestion, providing a clue that the bound residue of OCPs might be mobilized. This hypothesis was tested in this study for both OCPs and polycyclic aromatic hydrocarbons (PAHs). Three contaminated surface soil samples with different organic carbon (OC) contents were collected from the field, and extracted with a solvent with and without digestion in an in vitro gastrointestinal model. It was found that bound residues of OCPs and PAHs were mobilized to a certain extent during digestion. The ratios of the mobilized bound residues over the total quantities extracted after digestion (R(b)) varied from 0 to 0.96 for individual compounds. The R(b) was positively correlated with OC content. Among the five constitutes of digestive juice, bile salt was the only one that served to mobilize the bound residues and the extractability of bile salt was constant over a concentration range from 2 to 20 mg/mL. The mobilization process followed typical first-order kinetics. The calculated rate constants suggest that mobilization was fast and 90% of extracted bound residues of OCPs and PAHs were mobilized within 2.4 and 4.8 h, respectively.

Residues of hexachlorocyclohexane isomers (HCHs, including alpha-HCH, beta-HCH, gamma-HCH, and delta-HCH) in human milk of two populations from Beijing and Shenyang, China were studied. In addition to human milk samples from 76 women, 271 composite food samples covering major food categories were also collected for HCH analysis. The food consumption and social-demographic characteristics of the studied populations were investigated and dietary intakes of HCHs of the milk donors on an individual basis were calculated. The dependences of HCH concentration in the human milk on food consumption, dietary intake of HCHs, and demographic characteristics were studied. It was found that beta-HCH dominated the HCHs detected in the human milk. Although there were dramatic declines in HCHs in the human milk compared to historical data, the current levels (312 +/- 377 ng/g fat and 360 +/- 235 ng/g fat as the means and standard deviations for Beijing and Shenyang, respectively) were still much higher than those reported in other cities within China and around the world. It was revealed that the residual level of HCHs in the human milk was positively correlated (p < 0.001) to the quantities of food consumption. Milk, oil, vegetables, and fruits contributed a large portion of HCHs intake in Beijing, while cereals, milk, vegetables, oil, and meat were the most important dietary intake sources of HCHs in Shenyang. Both daily dietary intake of HCHs (p < 0.001) and body mass index (BMI, body weight divided by the squared height) (p < 0.01) were significantly correlated with human milk HCHs. A nonlinear model was developed to predict the residues of HCHs in human milk using both dietary intake and BMI as independent variables. Potential risk of the HCH exposure of breastfed infants is discussed.

A static in vitro gastrointestinal model was used to investigate the oral bioaccessibility of organochlorine pesticides (OCPs) including hexachlorocyclohexane isomers (HCHs) and dichlorodiphenyltrichloroethane and metabolites in contaminated soils with different organic matter contents. A key hypothesis tested was that a fraction of the mobilized contaminants is sorbed on the solid after digestion, and this fraction could be desorbed and become bioaccessible in the intestinal tract due to absorption of the dissolved fraction by the small intestine. The bioaccessibility would be underestimated if the sorbed fraction was separated from the fluid by centrifugation or filtration in an in vitro test. In our experiment, a procedure using multiple fluid-to-solid ratios was developed to characterize the sorption. It was found that 8-38% of the mobilized OCPs were sorbed on the residue and remained in the solid phase after the separation. Taking into consideration the sorbed fraction, the measured bioaccessibilities of the OCPs varied from 4% to 97% depending on the properties of the soils and the compounds. The enantiomeric ratios of chiral compounds studied were also determined to distinguish biotic (enzymatic) and abiotic (chemical extraction) processes in the in vitro digestion model. It was found that although alpha-HCH in the raw soils was racemic, (+)-alpha-HCH was enriched in the gastric digestive fluid but depleted in the intestinal digestive fluid.

This paper presents the results of an investigation on association between dietary intakes and human milk concentrations of dichlorodiphenyltrichloroethane and metabolites (DDTs) of two populations from Beijing and Shenyang, China. We analyzed human milk samples from 76 women and 287 composite food samples covering major food categories for concentrations of DDTs. We also collected information on food consumptions and calculated dietary intakes of DDTs of the participants on individual basis. The median values of the measured DDTs in human milk were 125 ng/g lipid and 132 ng/g lipid for the samples from Beijing and Shenyang, respectively. The mean (+/-standard deviation) daily dietary intakes of DDTs by the two groups were 32.0 +/- 14.2 ng/kg day and 27.9 +/- 11.3 ng/kg day, respectively. The temporal trends of decreasing in DDTs and increasing in DDE/DDT ratio suggested that the residuals were primarily from historical application. We found a significant correlation between human milk concentration and daily dietary intake of DDTs, while the dietary intake could explain 22% of the variation in the DDTs in human milk. In addition to dietary exposure, we also found that maternal body mass index (body weight divided by the squared height), body weight, body height, and mother's age contributed significantly to the variation of DDTs in human milk after intake normalization. The result of a probabilistic risk assessment indicated that the exposure of infants to DDTs through breast feeding would be a public health concern for years to come, although breast feeding is still recommended.

A USEPA, procedure, ISCLT3 (Industrial Source Complex Long-Term), was applied to model the spatial distribution of polycyclic aromatic hydrocarbons (PAHs) emitted from various sources including coal, petroleum, natural gas, and biomass into the atmosphere of Tianjin, China. Benzo[a]pyrene equivalent concentrations (BaPeq) were calculated for risk assessment. Model results were provisionally validated for concentrations and profiles based on the observed data at two monitoring stations. The dominant emission sources in the area were domestic coal combustion, coke production, and biomass burning. Mainly because of the difference in the emission heights, the contributions of various sources to the average concentrations at receptors differ from proportions emitted. The shares of domestic coal increased from approximately 43% at the sources to 56% at the receptors, while the contributions of coking industry decreased from approximately 23% at the sources to 7% at the receptors. The spatial distributions of gaseous and particulate PAHs were similar, with higher concentrations occurring within urban districts because of domestic coal combustion. With relatively smaller contributions, the other minor sources had limited influences on the overall spatial distribution. The calculated average BaPeq value in air was 2.54 +/- 2.87 ng/m3 on an annual basis. Although only 2.3% of the area in Tianjin exceeded the national standard of 10 ng/m3, 41% of the entire population lives within this area.