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[Display omitted] Reactions between 4-(propargyloxy)benzaldehyde with anthracene-9-carbaldehyde oxime or pyrene-1-carbaldehyde oxime in the presence of chloramine T in ethanol lead to new isoxazole-containing derivatives of benzaldehyde. The subsequent acid-catalyzed condensation of these compounds with 2-methylresorcinol in chloroform/trifluoroacetic acid mixtures affords novel calix[4]resorcinols with anthaceneand pyrene-ended isoxazole-containing fragments as all– cis (rccc) and cis–trans–trans (rctt) diastereoisomers, their ratios being dependent on the CF 3 CO 2 H percentage in the medium. The crystal structures of pyrene-ended isoxazole-containing benzaldehyde and corresponding calix[4]resorcinol rctt isomer have been established by single crystal X-ray diffraction. [ABSTRACT FROM AUTHOR]

The absolute configuration and stability of two thianthrene chiral sulfoxides has been determined by means of X-ray single-crystal structure determinations. The analyses and configurations allow verification that the diastereomeric sulfoxides are stable in solution and are not interconverting, which has been suggested in some studies of sulfoxides. The two thianthrene sulfoxides have slightly different Rf values, which allowed their separation using flash chromatography on silica. The spots run back-to-back, which posed a challenge for their separation. The pure, separated compounds in solution remain as separate, single spots on a Thin Layer Chromatography (TLC) plate. [ABSTRACT FROM AUTHOR]

The absolute configuration and stability of two thianthrene chiral sulfoxides has been determined by means of X-ray single-crystal structure determinations. The analyses and configurations allow verification that the diastereomeric sulfoxides are stable in solution and are not interconverting, which has been suggested in some studies of sulfoxides. The two thianthrene sulfoxides have slightly different Rf values, which allowed their separation using flash chromatography on silica. The spots run back-to-back, which posed a challenge for their separation. The pure, separated compounds in solution remain as separate, single spots on a Thin Layer Chromatography (TLC) plate.

The quinoxaline core is a promising scaffold in medicinal chemistry. Multiple quinoxaline derivatives, such as the topoisomerase IIβ inhibitor XK-469 and the tissue transglutaminase 2 inhibitor GK-13, have been evaluated for their antiproliferative activity. Previous work reported that quinoxaline derivatives bearing an oxirane ring present antiproliferative properties against neuroblastoma cell lines SK-N-SH and IMR-32. Likewise, quinoxalines with an arylethynyl group displayed promising antineoplastic properties against glioblastoma and lung cancer cell lines, U87-MG and A549 respectively. Here, 40 new quinoxaline derivatives bearing an oxirane ring were synthesized using a tetrakis(dimethylamino)ethylene (TDAE) strategy and a Sonogashira cross-coupling reaction. Each reaction with TDAE furnished a pair of diastereoisomers cis and trans. These new compounds formed two series according to the substitution of position 2 on the quinoxaline core, with chlorine or phenylacetylene respectively. Each of these isomers was evaluated for antiproliferative activity against neuroblastoma cell lines SK-N-SH and IMR-32 by MTT assay. All cell viability assay results were analyzed using R programming, as well as a statistical comparison between groups of compounds. Our evaluation showed no difference in drug sensitivity between the two neuroblastoma cell lines. Moreover, trans derivatives were observed to display better activities than cis derivatives, leading us to conclude that stereochemistry plays an important role in the antiproliferative activity of these compounds. Further support for this hypothesis is provided by the lack of improvement in antineoplastic activity following the addition of the phenylacetylene moiety, probably due to steric hindrance. As a result, compounds with nitrofuran substituents from the TDAE series demonstrated the highest antiproliferative activity with IC50 = 2.49 ± 1.33 μM and IC50 = 3.96 ± 2.03 μM for compound 11a and IC50 = 5.3 ± 2.12 μM and IC50 = 7.12 ± 1.59 μM for compound 11b against SK-N-SH and IMR-32, respectively. Furthermore, an in silico study was carried out to evaluate the mechanism of action of our lead compounds and predict their pharmacokinetic properties. [ABSTRACT FROM AUTHOR]

S-adenosyl-l-methionine (AdoMet), an important biological cofactor, exists in two chiral forms, (S,S)- and (R,S)-, only the former of which is biologically active. Here, we have developed a chromatographic method to obtain pure (S,S)-AdoMet using a single C18 column.

The quinoxaline core is a promising scaffold in medicinal chemistry. Multiple quinoxaline derivatives, such as the topoisomerase IIβ inhibitor XK-469 and the tissue transglutaminase 2 inhibitor GK-13, have been evaluated for their antiproliferative activity. Previous work reported that quinoxaline derivatives bearing an oxirane ring present antiproliferative properties against neuroblastoma cell lines SK-N-SH and IMR-32. Likewise, quinoxalines with an arylethynyl group displayed promising antineoplastic properties against glioblastoma and lung cancer cell lines, U87-MG and A549 respectively. Here, 40 new quinoxaline derivatives bearing an oxirane ring were synthesized using a tetrakis(dimethylamino)ethylene (TDAE) strategy and a Sonogashira cross-coupling reaction. Each reaction with TDAE furnished a pair of diastereoisomers cis and trans. These new compounds formed two series according to the substitution of position 2 on the quinoxaline core, with chlorine or phenylacetylene respectively. Each of these isomers was evaluated for antiproliferative activity against neuroblastoma cell lines SK-N-SH and IMR-32 by MTT assay. All cell viability assay results were analyzed using R programming, as well as a statistical comparison between groups of compounds. Our evaluation showed no difference in drug sensitivity between the two neuroblastoma cell lines. Moreover, trans derivatives were observed to display better activities than cis derivatives, leading us to conclude that stereochemistry plays an important role in the antiproliferative activity of these compounds. Further support for this hypothesis is provided by the lack of improvement in antineoplastic activity following the addition of the phenylacetylene moiety, probably due to steric hindrance. As a result, compounds with nitrofuran substituents from the TDAE series demonstrated the highest antiproliferative activity with IC50 = 2.49 ± 1.33 μM and IC50 = 3.96 ± 2.03 μM for compound 11a and IC50 = 5.3 ± 2.12 μM and IC50 = 7.12 ± 1.59 μM for compound 11b against SK-N-SH and IMR-32, respectively. Furthermore, an in silico study was carried out to evaluate the mechanism of action of our lead compounds and predict their pharmacokinetic properties.

A pair of new diastereoisomeric flavan, containing an additional phenylpropanoid (C6–C3) unit in the molecule, has been isolated from the leaves of Ilex centrochinensis. Their structures were identified by extensive spectral analysis and comparison with the data of known analogues. [ABSTRACT FROM AUTHOR]

[Display omitted] • Design of experiments allows to optimize the diastereoselectivity of the epoxidation. • The α face of the Δ5 steroids has a greater spatial for low-temperature epoxidation. • At room temperature the diastereoselectivity of epoxidation on Δ5 steroids is lost. • qNMR allows to optimize the use of statistical tools such as design of experiments. Diosgenin and its derivatives have proved a huge importance in diverse biological activities. The optimized production of the diastereoisomers of the epoxide of diosgenin acetate by means of mCPBA is reported herein. This transformation had a previous design of experiments using the application of a statistical factorial DoE of 4 parameters (nk), where one variable is varied at a time, while others stay constant. The temperature showed the greatest effect on the reaction yield; so, at 298 K the diastereomeric ratio 3 : 1 of α and β -epoxides, normally found, was raised to 1:1. Time was the second significant variable, but due to its high correlation with temperature, 30 min were required for a global 90% conversion at least. These diastereoisomers were characterized both isolated and in the mixtures obtained, to determine their antioxidant, antimicrobial and antiproliferative activity, finding a low antioxidant capacity by DPPH, but antimicrobial activity at the level of penicillin in gram negative bacteria by 1β better to 1α. The antiproliferative capacity was higher for diastereoisomer β , agreeing with the proportion of the mixture obtained by different conditions, increasing this in relation to the amount of this diastereoisomer present in hormone-dependent cancer cell lines such as Hela, PC-3 and MCF-7, with 10.0 µM obtained values of viability at 21.8 %, 35.8 % and 12.3 % respectively. DoE optimization allows to manipulate the ratio between diastereoisomers with the minimum number of experiments, extending the analysis of the effect of the ratio between diastereoisomers and the in silico potential as well as the biological activity. [ABSTRACT FROM AUTHOR]

Heterobimetallic derivatives of a bis(carborane), [μ7,8-(1′,3′−3′-Cl-3′-PPh3-closo-3′,1′,2′-RhC2B9H10)-2-(p-cymene)-closo-2,1,8-RuC2B9H10] (1) and [μ7,8-(1′,3′−3′-Cl-3′-PPh3-closo-3′,1′,2′-RhC2B9H10)-2-Cp-closo-2,1,8-CoC2B9H10] (2) have been synthesised and characterised, including crystallographic studies. A minor co-product during the synthesis of compound 2 is the new species [8-{8′-2′-H-2′,2′-(PPh3)2-closo-2′,1′,8′-RhC2B9H10}-2-Cp-closo-2,1,8-CoC2B9H10] (3), isolated as a mixture of diastereoisomers. Although, in principle, compounds 1 and 2 could also exist as two diastereoisomers, only one (the same in both cases) is formed. It is suggested that the preferred exopolyhedral ligand orientation in the rhodacarboranes in the non-observed diastereoisomers would lead to unacceptable steric crowding between the PPh3 ligand and either the p-cymene (compound 1) or Cp (compound 2) ligand of the ruthenacarborane or cobaltacarborane, respectively.

OBJECTIVE: To establish the method for mass concentration of lobaplatin in human plasma and hydrothorax by HPLC. The method was used for patients with lung cancer, and could provide basis for the clinical therapeutic drug monitoring (TDM). METHODS： Human plasma and hydrotliorax samples were centrifuged and extracted with acetonitrile. The Inertsil-ODS-SP column (250 mm x4. 6 mm, 5 μm) was used, the mobile phase were consisted of phosphate buffer (pH =6. 5) and acetonitrile (containing 0. 03% triethylamine) (V : V= 96 : 4) and flushed at a flow rate of 1 0 ml/min, the wavelength was 215 nm. RESULTS: The calibration curves were linear over a concentration range of 0. 1 μg/ml-80. 0 μg/ml in the hydrothorax and 0. 1 μg/ml-50. 0 μg/ml in the plasma respectively. The limit of detection (LOD) and limit of quantification (LOQ) was 0. 1 μgml and 0. 5 μgml in hydrotiiorax and plasma. CONCLUSIONS: A rapid HPLCmethod to detect the concentration of lobaplatin in human plasma and hydrothorax was established. Themethod is sensitive, stable with good reproducibility, selectivity and high accuracy, and could be successfully used for the determination of lobaplatin concentration in human plasma and hydrothorax so as to conduct the therapeutic drug monitoring and provide individualized therapy for lung cancer patients. [ABSTRACT FROM AUTHOR]

We herein report the synthesis and characterization of Ru(II)/amino acid complexes with general formula [Ru(AA-H)(dppb)(4-mebipy)](PF6), where AA-H means the deprotonated amino acids Gly, Ala, Val, Met, Trp, Tyr, and Ser; dppb is 1,4-bis(diphenylphosphino)butane and 4-mebipy = 4,4′-dimethyl-2,2′-bipyridine. The complexes were characterized by31P{1H},13C, and1H NMR spectroscopy, as well as X-ray crystallographic analysis of [Ru(DL-Ala-H)(dppb)(4-mebipy)]+, suggesting the presence of diastereoisomers. The complexes exhibit IC50values against breast tumor cells (MDA-MB-231) comparable with cisplatin. In addition, the Ru(II)-based complex with tryptophan inhibited tumor cell adhesion to collagen type I. Therefore, the use of ruthenium complexes containing amino acids can be an interesting tool for development of new therapeutic agents. [ABSTRACT FROM AUTHOR]

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Tetrabromobisphenol A (TBBPA) and hexabromocyclododecanes (HBCDs) were analyzed in 12 tissues of prey (mud carp) and predator (northern snakehead) fish from an e-waste area, South China. The TBBPA concentrations in different tissues ranged from 0.03 to 2.85 ng/g wet weight (ww) in mud carp and 0.04 to 1.30 ng/g ww in northern snakehead. The concentrations of HBCDs ranged from 0.07 to 96.9 ng/g ww in mud carp and 0.18 to 240 ng/g ww in northern snakehead. HBCD levels in tissues were correlated with lipid content for both fish species, while this correlation was only found in mud carp for TBBPA. Meanwhile, northern snakehead exhibited higher HBCD levels but lower TBBPA levels than mud carps. These observations are attributed to the more polar and reactive properties of TBBPA than HBCDs. α-HBCD was the predominant diastereoisomer of HBCDs in all tissues of mud carp and northern snakehead, except for chyme of mud carp. All the analyzed tissues in mud carp showed an enrichment of (+)-α-HBCD enantiomer with EF (enantiomeric fraction) values of 0.53-0.62, but that in northern snakehead showed an enrichment of (−)-α-HBCD enantiomer with EF values of 0.35-0.5. Considering the fact that the mud carp is one of the diet items of northern snakehead, the different enantiomer accumulation characteristics of α-HBCD between the two fish species in the present study indicated that prey and predator fish could prefer to biotransform different enantiomers of α-HBCD. [ABSTRACT FROM AUTHOR]

In order to elucidate the mechanism for diastereoisomer-specific toxicity and metabolism of hexabromocyclododecanes (HBCDs) in biota, zebrafish ( Danio rerio ) were exposed to different concentrations of individual HBCD diastereoisomers (α-, β- and γ-HBCD) in water for 7 and 21 d. We examined the gene expression of aryl hydrocarbon receptor (AHR) and cytochrome P450 (CYP), as well as ethoxyresorufin-O-deethylase (EROD) activity in zebrafish livers. Exposure to different HBCD diastereoisomers caused different expression of AHRs in zebrafish livers. For instance, 10 and 100 μg L −1 of α- and β-HBCD up-regulated the expressions of ahr1a and ahr1b in zebrafish liver, whereas 10 and 100 μg L − 1 of γ-HBCD down-regulated them after 7 d exposure. α-HBCD showed the most significant up-regulation of ahr1a and ahr1b expression, whereas γ-HBCD showed the most significant down-regulation of their expression among three HBCD diastereoisomers. Moreover, HBCDs could affect the expression of CYP1s as well as EROD activity in a gene-specific and diastereoisomer-specific manner. α-, β- and γ-HBCD inhibited cyp1a expression but enhanced the expression of cyp1b1 and cyp1c1. α-, β- and γ-HBCD showed different degrees of effect on the same CYP1 gene in a concentration-dependent way. The different effects of HBCD diastereoisomers on these genes we examined and EROD activity not only indicate diastereoisomer-specific toxic effect, but also in turn explain diastereoisomer-specific accumulation of HBCDs in zebrafish. [ABSTRACT FROM AUTHOR]

The preparation of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates from (E)-3-penten-1-ol is reported. The mesylate of (E)-3-penten-1-ol was converted into trans- or cis-2-methyl-3-hydroxytetrahydrofuran by oxidation with H2O2 and HCOOH or with KMnO4. cis- or trans-2-Methyltetrahydrofuran-3-thiol acetate was prepared by mesylation and an SN2 nucleophilic substitution with AcSH from trans- or cis-2-methyl-3-hydroxytetrahydrofuran respectively. The configuration of the products was confirmed by their synthesis. Olfactory evaluation of cis- and trans-2-methyltetrahydrofuran-3-thiol acetates indicated some differences both in odour feature and intensity. [ABSTRACT FROM AUTHOR]

Context: Vitex negundo Linn. (Verbenaceae) seeds are pepper substitute and occasionally used as a condiment for edible purposes. The seeds also find use for analgesia, sedation, rheumatism and joint inflammation in folk medicine. Objective: To isolate and characterize bioactive constituents from V. negundo seeds. Materials and methods: The ethanol extract of V. negundo seeds was subjected to repeated column chromatography. Chemical structures were elucidated by detailed spectroscopic analyses on the basis of NMR, IR, and MS data. Several pathogenic fungi isolates were employed to evaluate the antifungal activity of the isolated compound. Results: Chemical investigations of the seed extract afforded a new labdane diterpenoid, named negundol ( 1a + 1b), as an inseparable mixture of two diastereoisomers in a 5:4 ratio. Their structures were identified as ( rel 3 S, 5 S, 8 R, 9 R, 10 S, 13 S, 16 S)-3-acetoxy-9, 13-epoxy-16-hydroxy-labda-15, 16-olide ( 1a), and ( rel 3 S, 5 S, 8 R, 9 R, 10 S, 13 S, 16 R)-3-acetoxy-9, 13-epoxy-16-hydroxy-labda-15, 16-olide ( 1b). Compound 1 was active as an antifungal agent with MIC80 values in the range of 16-64 μg/mL. Discussion and conclusion: The presence of compound 1 in V. negundo is of chemotaxonomic significance, since plants under the genus Vitex are chemically characterized with labdane diterpenoids. Compound 1 exhibited potential antifungal activity and may be considered a lead compound for promising antifungal agent. [ABSTRACT FROM AUTHOR]

Abstract: Five new furostanol saponins (1–5), together with three known compounds (6–8) were obtained from the n-butanol soluble fraction of ethanol extract from Tupistra chinensis. Their structures were determined on the basis of chemical methods and spectral data. The isolated compounds were tested in vitro for their cytotoxic activities against the A549, HepG 2 and Caski cancer cell lines. Among them, compounds 6, 7, and 8 showed cytotoxicity against A549 cancer cell lines with IC50 values of 6.6, 6.7 and 29.1μM, respectively. [Copyright &y& Elsevier]

Abstract: Hexabromocyclododecanes (HBCDs) are now emerging ubiquitous contaminants due to their wide usage, persistence and toxicities. To investigate the bioaccumulative characteristics of HBCDs, sediments, Winkle (Littorina littorea), crucian carp (Carassius carassius) and loach (Misgurnus anguillicaudatus) were collected from two streams near an E-waste dismantling site in China, and HBCD exposure test was then conducted on Chinese rare minnow. The concentration of HBCDs was 14ngg−1 dry weight in sediments, 186, 377 and 1791ngg−1 lipid weight in winkle, crucian carp and loach, respectively. γ-HBCD was found to be the dominant diastereoisomer in the sediments (63% of total HBCDs). However, α-HBCD was selectively accumulated in the biotic samples and contributed to 77%, 63% and 63% of total HBCDs in winkle, crucian carp and loach, respectively. Moreover, an enrichment of (−)-enantiomers of α- and γ-HBCD were found in the winkle. The reverse results were observed in the crucian carp and loach. Similar observations of diastereoisomeric and enantiomeric composition were obtained in Chinese rare minnow with those found in the crucian carp and loach. These results indicate that the freshwater species from the streams are contaminated by HBCDs. α-HBCD can be selectively accumulated in organisms and the accumulative characteristics are enantioselective among species. [Copyright &y& Elsevier]

Chiral recognition of phenylalanine (Phe) was achieved in the gas phase by electrospray ionization Q-TOF tandem mass spectrometry. In this method, two central ions, i.e. proton and divalent copper, were used and chiral crown ether, (+)-2,3,11,12-tetracarboxylic acid-18-crown-6 (18-C-6-TCA), was used as a chiral host. Dimeric complexes were readily formed by electrospray ionization of a methanol/water (50/50, V/ V) solution containing central ions, Phe and 18-C-6-TCA. The dimeric complex included proton-bound (18-C-6-TCA)(Phe)H+ and copper-bound deprotonated [Cu2+(18-C-6-TCA)(Phe)-H]+ ions were mass selected and then collided with Ar in the CID experiments. The chiral recognition capability of these complexes was evaluated using the relative abundance of daughter ion to parent ion. A higher degree of chiral recognition ability was observed with Cu2+ compared to that of H+. Different central ions exhibited distinctive dissociation pathways and unique chiral recognition characteristics. The chiral recognition mechanism was also discussed in detail with the help of the structure of copper-bound complex predicted by theoretical calculation. [ABSTRACT FROM AUTHOR]

Abstract: A chiral HPLC method was validated and successfully applied for the determination of formoterol stereoisomers and their inversion products in an aqueous matrix stored at 5–70°C up to 3 weeks. Analysis was performed on a Chiral-AGP column (100×4-mm, 5-μm) using a variable mixture of mobile phase A (50-mM sodium phosphate buffer, pH 7.0) and B (10% v/v IPA) at a flow rate of 1.3mlmin−1, and UV detection at 242nm. All four formoterol stereoisomers were adequately resolved with acceptable detection and quantitation limits varying from 0.01–0.04μg/ml and 0.04–0.1μg/ml, respectively. The method showed acceptable accuracy (≥88%), precision (RSD≤8.5%) and good linearity (r 2 ≥0.9999) over the concentration range investigated. While interconversion at 5±3°C and 25±2°C/60% RH ±5% RH was too low to be determined accurately within the study period, chiral inversion of formoterol stereoisomers measured at high temperatures followed the first order rate kinetics and occurred at a single chiral center, resulting in the reversible formation of diastereoisomers, (R,R)↔(S,R) and (S,S)↔(R,S). No enantiomerization or diastereomerization occurred. There was no significant difference in inversion of the active components in racemic (R,R/S,S)-formoterol fumarate and the single isomer (R,R)-arformoterol tartrate drug formulations, and both drugs are expected to maintain their stereochemical integrity throughout the proposed shelf-life at the recommended storage condition (5±3°C). [Copyright &y& Elsevier]

Abstract: Selected synthetic ways of preparation of chiral alcohols are reviewed. In this review, special attention is focused on preparation of enantiomerically pure cycloalkanols by employing enzymic processes, which are considered to be advanced for their sustainable and ‘green’ nature. Selected processes reviewed are: (a) enzymic resolution through transesterification of racemic alcohols, (b) enzymic resolution through hydrolysis of convenient racemic esters, and (c) enzymic reduction of prochiral ketones. Principles of prediction of the absolute configuration of the products are presented. Due to a number of recent reviews on this topic only a limited number of examples are shown in this review. [Copyright &y& Elsevier]

Abstract: Chiral sulfoximines have applications as transition-state mimicking enzyme inhibitors, as peptide isosteres and as chiral auxiliaries in synthesis. To access the required O-protected 4-(arylsulfonimidoyl)butane-1,2,3-triols, 4S,5S-di(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane (prepared from diethyl R,R-tartrate) was converted into its monobenzyl ether. Mitsunobu-like coupling with thiophenols gave 4S,5R-4-(benzyloxymethyl)-2,2-dimethyl-5-(arylthiomethyl)-1,3-dioxolanes. Sulfoxidation and S-imination (trifluoroacetamide, iodosobenzene diacetate, rhodium acetate) proceeded without stereoselectivity, giving inseparable diastereomeric mixtures of 4S,5R,S(±)-4-(benzyloxymethyl)-2,2-dimethyl-5-(N-(trifluoroacetyl)arylsulfonimidoylmethyl)-1,3-dioxolanes. Removal of the trifluoroacetyl protection allowed chromatographic separation of the diastereomeric 4S,5R,S(±)-4-(benzyloxymethyl)-2,2-dimethyl-5-(arylsulfonimidoylmethyl)-1,3-dioxolanes. The configurations at sulfur were determined by X-ray crystallography and some analysis of the solution and solid-state conformations was carried out. The resulting O-protected 4-(arylsulfonimidoyl)butane-1,2,3-triols are of use in developing enzyme inhibitors. [Copyright &y& Elsevier]

Abstract: A series of the protected alkyl glycosides 5a/5b–12a/12b was synthesized from the parent isomeric alcohols (insect juvenile hormone bioanalogs; juvenoids), 4-[4′-(2″-hydroxycyclohexyl)methylphenoxy]-3-methyl-but-2-enoic acid ethyl ester (1a/1b–4a/4b; racemic structures) and (1a–4a; enantiopure structures). Cadmium carbonate was used as a promoter of this Koenigs–Knorr reaction, and the products were obtained in 82–92% yields. Deprotection of the carbohydrate functionality of 5a/5b–12a/12b was carefully performed using ethanolysis in the presence of zinc acetate, due to the presence of another ester functionality in the aglycone part of the molecule of protected alkyl glycosides. Resulting alkyl glycosides 13a/13b–20a/20b (diastereoisomeric mixtures) and 13a–20a (enantiopure compounds), biochemically activated hormonogenic compounds (juvenogens), were obtained in 82–93% yields. Finally, chiral HPLC separation of the diastereoisomeric mixtures of alkyl glycosides was applied to get sufficient quantities of the respective enantiomers 13b–20b of the alkyl glycosides for their structure elucidation and 13C chemical shift assignment by 1H and 13C NMR spectroscopy. Partial introductory entomological screening tests of the target alkyl glycosides 13a/13b–20a/20b were performed on the red firebug (Pyrrhocoris apterus). The results of this biological testing clearly demonstrated the time-extended effect of several juvenogens on P. apterus due to their biochemical activation, i.e., hydrolysis of the juvenogen molecule, which results in liberation of the biologically active juvenoid in the insect organism. [Copyright &y& Elsevier]

Abstract: During the investigation of ester derivatives (juvenogens, biochemically activated insect hormonogenic compounds) of biologically active alcohols with potential application in insect pest control, a need for availability of all existing stereoisomers of ethyl N-{2-[4-(2-butanoyloxycyclohexyl)methyl]phenoxy}ethyl carbamate occurred. They were synthesized from their chiral precursors, the corresponding stereoisomers of 2-(4-methoxybenzyl)cyclohexyl butanoate, by removing their protecting group (methyl), and by subsequent condensation of the aromatic hydroxyl moiety with ethyl N-(2-bromoethyl) carbamate. The requested enantiomers of 2-(4-methoxybenzyl)cyclohexyl butanoate were obtained by a Candida antarctica lipase-mediated transesterification and chiral resolution of the respective racemic cis- and trans-isomers of 2-(4-methoxybenzyl)cyclohexanol either directly or after a subsequent chemical esterification of the chiral precursor. In this synthesis, two convenient butanoic acid activating esters, vinyl butanoate and 2,2,2-trifluoroethyl butanoate, were employed, and the chiral precursors in the synthesis of the target molecules were obtained in 41–48% yields (i.e., 82–96% conversion), and with enantiomeric purity ee=96–98%, respectively. The enantiomeric purity of the products was determined by chiral HPLC analysis, and their absolute configuration was assigned on the basis of analyzing the 1H and 19F NMR spectra of their diastereoisomeric Mosher acid (3,3,3-trifluoromethyl-2-methoxy-2-phenylpropanoic acid) esters. [Copyright &y& Elsevier]

Abstract: The possibility of using capillary electrophoresis as an alternative technique to HPLC for the separation of pronucleotide diastereoisomers of AZT was investigated. In the pH range 6.2–7.2 where the analytes are stable, a chiral additive, carboxymethyl-β-CD, was found appropriate to enable the separation of the uncharged diastereoisomers. An experimental design strategy was used to study the influence of several parameters (CD and phosphate buffer concentration, methanol content of the electrolyte, injected volume, capillary length, electric field and separation temperature) on the separation and find suitable analytical conditions for monitoring the prodrugs in cell extracts. The diastereoisomers of the three tBuSATE phenylphosphotriester derivatives of AZT studied could be fully resolved within short analysis time (less than 10min). Method validation results showed satisfactory results for linearity, accuracy and repeatability. [Copyright &y& Elsevier]

Abstract: The structures of four new diastereoisomeric triterpenoidal saponins Julibroside J5, J8, J12 and J13 (1–4) isolated from Albizia julibrissin Durazz. (Leguminosae) have been determined on the basis of comprehensive spectroscopic analysis and chemical degradation. Julibroside, J8 and J13 showed marked cytotoxic activities against Bel-7402 cancer cell line at 100μg/mL. [Copyright &y& Elsevier]

A comparative study of two modifications of enzymic reduction of ethyl N-\2-\4-[(2-oxo-cyclohexyl)methyl]phe- noxy\ethyl\ carbamate (1), an insect juvenile hormone bioanalog, was performed using Saccharomyces cerevisiae in two bioreactors of different size, 250-ml shake-flask and 1-l fermenter. The two major products of this reduction were obtained in 45–49% (w/w) yields but with > 99% enantiomeric purity. Their absolute configurations were assigned as ethyl (1S,2S)-N-\2-\4-[(2-hydroxycyclohexyl)methyl]phenoxy\ethyl\carbamate (2a) and ethyl (1R,2S)-N-\2-\4-[(2-hydroxycyclohexyl)methyl]phenoxy\ethyl\carbamate (3a). [ABSTRACT FROM AUTHOR]

The enantioselectivity potential of five strains of Saccharomyces cerevisiae was studied for the reduction of ethyl N-{2-{4-[(2-oxocyclohexyl)methyl]phenoxy}ethyl} carbamate (1), an insect juvenile hormone bioanalog. The products of the reaction, the cis and trans isomers of ethyl N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl} carbamate (2 and 3), were obtained in 45–49% (w/w) chemical yields and with 79 to > 99% enantiomeric purity values. The absolute configurations of the major products were assigned as ethyl (1S,2S)-N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl} carbamate (2) and ethyl (1S,2R)-N-{2-{4-[(2-hydroxycyclohexyl)methyl]phenoxy}ethyl} carbamate (3). The products 2 and 3 belong to the series of the chiral insect juvenile hormone analogs. [ABSTRACT FROM AUTHOR]

South Korea is one of the largest consumers of flame-retardants worldwide. In this study, water, sediment, and biota samples were collected from a highly industrialized lake to investigate contamination, isomeric profiles, source, and the bioaccumulation potential of hexabromocyclododecanes (HBCDDs). Almost all of the sediments were severely contaminated by HBCDDs, which were some of the highest global levels compared to those found in previous studies. The highest concentrations and similar profiles to those of technical mixtures of HBCDDs were observed in creeks passing through industrial complexes, indicating on-going contamination by high consumption of HBCDDs from industrial activities. γ -HBCDD was dominant in water and sediment, whereas α -HBCDD was dominant in fish and shellfish. The diastereoisomeric profiles of HBCDDs in multiple matrices were influenced by proximity to industry and chemical properties. In-situ biota-sediment accumulation factors of α -HBCDDs were > 1 in benthic species, implying that HBCDDs are of great concern in sedimentary environments. • HBCDD isomers were detectable in multiple matrices from an industrialized lake. • Severe HBCDD contamination was identified in creeks near industrialized complexes. • Different diastereoisomeric distributions were observed in multiple matrices. • Diastereoisomeric HBCDD profiles were governed by sources and chemical properties. • In-situ BSAFs of α -HBCDD exceeded 1 for benthic species. [ABSTRACT FROM AUTHOR]

• Efficient and facile synthesis of novel sulfoxide bicalutamide derivatives. • Identification of compound 27 and 28 with enhanced anticancer activity across four PC cell lines (22Rv1, DU-145, LNCaP and VCap) compared to bicalutamide and enzalutamide. • Separation of three pairs of sulfoxide diastereoisomers and NMR data comparison. • X-ray diffraction crystal structure analysis confirms configuration assignment at the chiral sulfur and carbon centers. • Molecular modelling study of the four diastereoisomers of compound 28. The androgen receptor (AR) is a pivotal target for the treatment of prostate cancer (PC) even when the disease progresses toward androgen-independent or castration-resistant forms. In this study, a series of sulfoxide derivatives were prepared and their antiproliferative activity evaluated in vitro against four different human prostate cancer cell lines (22Rv1, DU-145, LNCaP and VCap). Bicalutamide and enzalutamide were used as positive controls. Compound 28 displayed significant enhancement in anticancer activity across the four PC cell lines with IC 50 = 9.09 – 31.11 µM compared to the positive controls: bicalutamide (IC 50 = 45.20 –51.61 µM) and enzalutamide (IC 50 = 11.47 – 53.04 µM). Sulfoxide derivatives of bicalutamide were prepared efficiently from the corresponding sulfides using only one equivalent of m CPBA, limiting the reaction time to 15–30 min and maintaining the temperature at 0 °C. Interestingly, three pairs of sulfoxide diastereomers were separated and NMR comparison of their diastereotopic methylene (CH 2) group is presented. X-ray diffraction crystal structure analysis provided relative configuration assignment at the chiral sulfur and carbon centres. Molecular modelling study of the four diastereoisomers of compound 28 is described. [ABSTRACT FROM AUTHOR]

Abstract: The 1,2-aminoalcohol moiety is widely present in compounds possessing pharmaceutically and biologically interesting properties During this work, we targeted the ring opening of the racemic styrene oxide by a chiral amine. In aqueous medium, a mixture of diastereoismers consisting largely of 2-N [1-phenylethyl] amino-1-phenylethanol 1 was obtained. The use of silica in the reaction permits the formation of mixture of diastereoisomers, but, contrary to aqueous solution, the diastereoisomer 2-N [1-phenylethyl] amino-2- phenylethanol 2 was majority. On the other hand, the reaction of ring opening under acidic conditions led to a regiospecific compound, particularly in the presence of Lewis acids, which only leads to the diastereoisomer 2 . [ABSTRACT FROM AUTHOR]

Heterobimetallic derivatives of a bis(carborane), [μ7,8-(1′,3′−3′-Cl-3′-PPh3-closo-3′,1′,2′-RhC2B9H10)-2-(p-cymene)-closo-2,1,8-RuC2B9H10] (1) and [μ7,8-(1′,3′−3′-Cl-3′-PPh3-closo-3′,1′,2′-RhC2B9H10)-2-Cp-closo-2,1,8-CoC2B9H10] (2) have been synthesised and characterised, including crystallographic studies. A minor co-product during the synthesis of compound 2 is the new species [8-{8′-2′-H-2′,2′-(PPh3)2-closo-2′,1′,8′-RhC2B9H10}-2-Cp-closo-2,1,8-CoC2B9H10] (3), isolated as a mixture of diastereoisomers. Although, in principle, compounds 1 and 2 could also exist as two diastereoisomers, only one (the same in both cases) is formed. It is suggested that the preferred exopolyhedral ligand orientation in the rhodacarboranes in the non-observed diastereoisomers would lead to unacceptable steric crowding between the PPh3 ligand and either the p-cymene (compound 1) or Cp (compound 2) ligand of the ruthenacarborane or cobaltacarborane, respectively. [ABSTRACT FROM AUTHOR]