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In carbohydrate chemistry, the stereoselective synthesis of 1,2- cis -glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2- cis - β -D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain β -stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of β -D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2- trans -glycosylation and C2 epimerization. This review elaborates on the advancements in β -D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans. [ABSTRACT FROM AUTHOR]

The hazards of man-made chiral compounds are of great public concern, with reports of worrying stereoselective compounds and an urgent need to assess their transport. This study evaluated the transport of 2-arylpropionic acid derivatives enantiomers (2-APA) in porous media under a variety of solution chemistry conditions via column packing assays. The results revealed the introduction of Malic acid (MA) enantiomers enhanced the mobility of 2-APA enantiomers, but the enhancement effect was different for different 2-APA enantiomers. Batch sorption experiments confirmed that the MA enantiomers occupied the sorption site of the quartz sand, thus reducing the deposition of the 2-APA enantiomer. Homo- or heterochirality between 2-APA and MA dominates the transport of 2-APA enantiomers, with homochirality between them triggering stronger retention and vice versa. Further evaluating the effect of solution chemistry conditions on the transport of 2-APA enantiomers, increased ionic strength attenuated the mobility of 2-APA enantiomers, whereas introduced coexisting cations enhanced the retention of 2-APA enantiomers in the column. The redundancy analyses corroborated these solution chemistry conditions were negatively correlated with the transport of 2-APA enantiomers. The coupling of pH and these conditions reveals electrostatic forces dominate the transport behavior and stereoselective interactions of 2-APA enantiomers. Distinguishing the transport of enantiomeric pair helps to understand the difference in stereoselectivity of enantiomers and promises to remove the more hazardous one. [Display omitted] • Stereoselectivity force of 2-APA and MA depend on homo- or heterochirality among them. • Increased ISs and introduction of coexisting cations weaken chiral interactions. • Enhanced electrostatic forces weaken chiral interactions and guide transport of 2-APA. • Divalent ions increase the retention of 2-APA in the column via bridging effects. [ABSTRACT FROM AUTHOR]

Talaromyces islandicus is a unique fungus that produces more than 20 numbers of anthraquinones (AQs) and their dimeric natural products, bisanthraquinones (BQs) . These compounds share a 9,10-anthracenedione core derived from emodin. The biosynthetic pathway of emodin has been firmly established, while that of other AQs and BQs is still unclear. In this study, we identified the biosynthetic gene clusters for chrysophanol and skyrin. The function of key modification enzymes was examined by performing biotransformation experiments and in vitro enzymatic reactions with emodin and its derivatives, allowing us to propose a mechanism for the modification reactions. The present study provides insight into the biosynthesis of AQs and BQs in T. islandicus . [ABSTRACT FROM AUTHOR]

A stereoselective chiral Lewis acid promoted reaction of siloxydiene (±)- 13 and dienophile complex 18 , gave a 4:1 mixture of urdamycinone B (1) and its C-3 epimer (24) in several steps in 12% overall yield. Separation of these products was achieved by high performance liquid chromatography (HPLC). [ABSTRACT FROM AUTHOR]

Ibuprofen (IBU), as a commonly used non-steroidal anti-inflammatory drug (NSAID) and pharmaceutical and personal care product (PPCP), is frequently prescribed by doctors to relieve pain. It is widely released into environmental water and soil in the form of chiral enantiomers by the urination and defecation of humans or animals and by sewage discharge from wastewater treatment plants. This study focused on the alteration of metabolism in the adult zebrafish ( Danio rerio ) brain after exposure to R-(-)-/S-(+)-/rac-IBU at 5 μg L −1 for 28 days. A total of 45 potential biomarkers and related pathways, including amino acids and their derivatives, purine and its derivatives, nucleotides and other metabolites, were observed with untargeted metabolomics. To validate the metabolic disorders induced by IBU, 22 amino acids and 3 antioxidant enzymes were selected to be quantitated and determined using targeted metabolomics and enzyme assay. Stereoselective changes were observed in the 45 identified biomarkers from the untargeted metabolomics analysis. The 22 amino acids quantitated in targeted metabolomics and 3 antioxidant enzymes determined in enzyme assay also showed stereoselective changes after R-(-)-/S-(+)-/rac-IBU exposure. Results showed that even at a low concentration of R-(-)-/S-(+)-/rac-IBU, disorders in metabolism and antioxidant defense systems were still induced with stereoselectivity. Our study may enable a better understanding of the risks of chiral PPCPs in aquatic organisms in the environment. [ABSTRACT FROM AUTHOR]

Stereoselective bioaccumulation, elimination, metabolomic and lipidomic responses of earthworm Eisenia fetida exposed to chiral polychlorinated biphenyl (PCB) 91 in an earthworm-soil system were investigated. Preferential bioaccumulation of (−)-PCB 91 and elimination of (+)-PCB 91 were observed following 50 and 500 μg/kg dwt exposures. Enantiomer fraction (EF) values decreased over time during the uptake and elimination periods. Metabolomics and lipidomics techniques based on ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) revealed significant changes in 108 metabolites after earthworms exposure to (+)-, (−)-, and (±)-PCB 91, compared to control groups. Forty two of these metabolites were identified as amino acids, nucleosides, fatty acids, dicarboxylic acids, vitamins or others. Lysophospholipids including six lysophosphatidylcholines (LPC), six lysophosphatidylethanolamine (LPE), eight lysophosphatidylinositol (LPI) and five lysophosphatidylserine (LPS) were also differentially expressed between exposure and control groups. Alterations in the levels of metabolites and lipids indicated stereoselective effects of chiral PCB 91 on earthworm amino acid, energy, and nucleotide metabolism, neurodevelopment and gene expression. Overall, the effects of (+)-PCB 91 were more pronounced than that of (−)- and (±)-PCB 91. [ABSTRACT FROM AUTHOR]

Pesticides and heavy metals commonly coexist in soil. In this study, the influence of Cd and Cu on the toxicity of rac -dinotefuran and the enantioselective behavior of dinotefuran enantiomers in soil-earthworm microcosms were investigated. The acute toxic tests showed that S -dinotefuran has higher toxic than that of R -dinotefuran. The rac -dinotefuran and Cd has an antagonistic effect on earthworms, and the Cu and rac -dinotefuran has a synergistic effect. Earthworms maybe promoted the enantioselective behavior of dinotefuran in soil. Co-exposure to Cd or Cu inhibited the dissipation of dinotefuran enantiomers (S -dinotefuran and R -enantiomers), and slightly reduced the enantioselectivity in soil. The earthworms were found to be preferentially enriched with S -dinotefuran. However, Cd or Cu attenuated the accumulation of dinotefuran enantiomers in earthworms and decreased the enantioselectivity. The effect of Cd and Cu on the environmental behaviors of dinotefuran enantiomers were correlated positively with the dose of Cd/Cu. These results showed that Cd and Cu alter the environmental behaviors and the toxicity of dinotefuran enantiomers in soil-earthworm microcosms. Thus, the influence of coexistent heavy metals on the ecological risk assessment of chiral pesticides should be considered. [Display omitted] • Toxicity of rac -dinotefuran with Cd is antagonistic, while that with Cu is synergistic. • Cu/Cd decelerates dinotefuran degradation in soil. • Earthworms in soil lead to EF increase of dinotefuran enantiomers. • Cd/Cu reduces the accumulation of dinotefuran enantiomers in earthworm. • Cd/Cu decreases the enantioselectivity of dinotefuran enantiomers in earthworm. [ABSTRACT FROM AUTHOR]

[Display omitted] • Metadynamic simulation of the stereoselectivity for Biginelli reaction mixture with 4-hydroxy- l -proline-containing podands is carried out. • The availability of diastereotopic sides at the stage of reactant diffusion is an important factor for understand the features of asymmetric centers formation. • Difference in the influence on stereoselectivity for the base and salt forms of 4-hydroxy- l -proline containing podands are established. The synthesis and theoretical study of the stereoselectivity of Biginelli reaction with chiral inductors based on 4-hydroxy- l -proline podands with four oxyethylene moieties have been performed. The predominant formation of the iminium intermediate during the interaction of the podand salt form with benzaldehyde was experimentally shown. Metadynamic simulation of reaction mixture with 4-hydroxy- l -proline-containing podand in salt and base forms allowed us to compare the probability of reactants approach from re- and Si- sides on the diffusion stage. We modeled the arrangement of reactants in the pre-reactional stage of alternative steps that could have a key effect on enantiomeric excess of 1,4-dihydropyrimidinone. Results showed that the interaction of a podand-acetoacetate adduct with N -benzylideneurea was preferred, when the podand was in a base form, while for a salt form, the intereaction with benzaldehyde was more favorable, which led to higher stereoselectivity. The effect of intermolecular interactions on the stabilization of prereaction states was analyzed. [ABSTRACT FROM AUTHOR]

Stereoselectivity in bioaccumulation and excretion of stereoisomers of epoxiconazole by mealworm beetle (Tenebrio molitor) larvae through dietary exposure was investigated. Liquid chromatography tandem mass spectrometry (HPLC−MS/MS) method that use a ChiralcelOD-3R[cellulosetris-Tris-(3,5-dichlorophenyl-carbamate)] chromatography column was applied to carry out chiral separation of the stereoisomers. Wheat bran was spiked with racemic epoxiconazole at two dose levels of 20 mg/kg and 2 mg/kg (dry weight) to feed T. molitor larvae. The results showed that both the doses of epoxiconazole were taken up by Tenebrio molitor larvae rapidly at the initial stages. There was a significant trend of stereoselective bioaccumulation in the larvae with a preferential accumulation of (−)-epoxiconazole in the 20 mg/kg dose. The stereoselectivity in bioaccumulation in the 2 mg/kg dosage was not obvious compared to the 20 mg/kg group. Results of excretion indicated an active excretion is an important pathway for the larvae to eliminate epoxiconazole which was a passive transport process with non stereoselectivity. The faster elimination might be the reason for the low accumulation of epoxiconazole, as measured by bioaccumulation factor (BAF). [ABSTRACT FROM AUTHOR]

In this research, Chinese lizards (Eremias argus) were chosen as laboratory animal to evaluate the stereoselectivity in the processes of metabolism, distribution, and bioaccumulation of triadimefon. A validated chiral high-performance liquid chromatography coupled with triple quadruple mass spectrometry (HPLC–MS/MS) method was developed for determining enantiomers’ residues of parent compound triadimefon and its metabolite triadimenol in lizard blood and tissues. Pharmacokinetic results of single-does exposure suggested that S-(+)-triadimefon was metabolized easier than R-(−)-triadimefon, and RR-(+)-triadimenol was the main metabolic product of triadimefon. During the continuous exposure of two dose (40 mg/kgbw·d and 200 mg/kgbw·d), enantiomers of triadimefon and triadimenol were detected in all body compartments, with the highest triadimefon concentrations in brain. However, the triadimenol concentrations were not significantly different among the compartments. The concentrations of RS-(+)-triadimenol were negative correlated with concentrations of RR-(+)-triadimenol both in blood ( r =−0.775, p =0.024) and liver ( r =−0.834, p =0.02) in 200 mg/kgbw·d group, which indicates that chiral conversion between enantiomers of triadimenol might exist in the metabolic process of triadimefon. In all the processes, the enantiomer fractions (EFs) of R-(−)-triadimefon and RR-(+)-triadimenol were significantly different from their natural ratios, 0.5 and 0.1, respectively, which proved that metabolism, bioaccumulation, and distribution of triadimefon and triadimenol in lizards were enantioselective. These results help enrich and supplement the knowledge of the stereoselective behaviour of triadimefon and triadimenol in reptile. [ABSTRACT FROM AUTHOR]

Abstract: The protein binding of non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac with human serum albumin (HSA) was investigated using indirect chiral high performance liquid chromatography (HPLC) and ultrafiltration techniques. S-(–)-1-(1-naphthyl)-ethylamine (S-NEA) was utilized as chiral derivatization reagent and pre-column derivatization RP-HPLC method was established for the separation and assay of the three pairs of enantiomer. The method had good linear relationship over the investigated concentration range without interference. The average extraction efficiency was higher than 85% in different systems, and the intra-day and inter-day precisions were less than 15%. In serum albumin, the protein binding of etodolac enantiomers showed significant stereoselectivity that the affinity of S-enantiomer was stronger than R-enantiomer, and the stereoselectivity ratio reached 6.06; Flurbiprofen had only weak stereoselectivity in HSA, and ketoprofen had no stereoselectivity at all. Scatchard curves showed that all the three chiral drugs had two types of binding sites in HSA. [Copyright &y& Elsevier]

Automated parallel synthesis with multivariate analysis was employed in the optimization of a Pd-catalyzed three-component cascade reaction of 7-buta-2,3-dienyl-1,3-dimethyl-3,7-dihydropurine-2,6-dione with iodobenzene and morpholine (see ). Initially a range of reaction factors were analyzed using experimental design to optimize for selectivity, conversion, and impurity levels. Solvents and bases were screened separately as the substantial number of discrete variables involved is unsuited to the fractional factorial design used. Instead, a solvent principal component analysis (PCA) model was used in selection of solvents for screening, so gaining maximum variation in solvent properties. Similarly, tertiary amines were chosen by pKa for screening as bases alongside inorganic salts. This investigation yielded two-fold results, not only in enhancement of the reaction selectivity, but since significantly different findings were obtained on changing the solvent, the importance of the sequence of experimentation is also emphasized. [Copyright &y& Elsevier]

[Display omitted] Alkene is an attractive substrate for chemists due to its easy availability and reactivity towards large number of reactants affording diverse range of organic compounds. It reacts under ionic and free radical mechanisms including single electron transfer (SET). In this review, strategies used for C–C and C-heteroatom functionalization of alkene has been discussed with emphasis on the regio, stereoselectivity, mechanistic detail and sustainability aspects. These strategies mainly follow the free radical mechanism, and the highly reactive carbon radicals show uncontrollable regio- and stereoselectivities. Thus these strategies still need to be focused; especially in the asymmetric versions. The regio- and stereoselectivities of functionalization of alkenes have been highlighted and debated. In addition, the hazardous reagents such as Cl 2 , Br 2 I 2 , CO, peroxides, and benzene have also been discussed with the emphasis on their impact on the environment. Their plausible green alternatives have also been suggested, such as MX as halogen replacement; CO surrogates (formaldehyde etc.); sustainable aromatic solvents as benzene replacement. The non-green strategies relying on pre-formed silyl hydride and their green alternative strategies such as transfer hydrogenations have also been indicated. The applications of the functionalization of alkenes for the total synthesis of bioactive compounds have also been discussed in detail. In addition, future perspectives are also highlighted for further developments in the functionalization of alkenes. [ABSTRACT FROM AUTHOR]

The article discusses research which examines the stereochemical differentiation in the cyclopropanated glucopyranose derivatives' Simmons-Smith reaction as molecular probes for glycosidases. The study showed that the reaction mechanism for cellulases is indispensable in designing its artificial mutants in higher stability than those of natural cellulases. It revealed that glucopyranose derivatives were synthesized to mimic the unstable transition state conformation of enzymatic hydrolysis.

A series of 4-hydroxyl-Δ 2 -isoxazol-6(6a H )-one derivatives was prepared by magnesium ion-mediated diastereoface-selective 1,3-dipolar cycloaddition of aromatic nitrile oxides with pyrrolidinone derivatives. The reaction of 4-hydroxyl-Δ 2 -isoxazol-6(6a H )-one derivatives with dimethylsulfoxide and oxalyl chloride under Swern conditions led to a Δ 2 -isoxazole-4,6(5 H ,6a H )-dione. [ABSTRACT FROM AUTHOR]