Main Diastereoisomers Research Articles

Spatial and temporal change of tetrabromobisphenol A and hexabromocyclododecane in mangrove sediments from the Pearl River Estuary, South China

Spatial and temporal trends of tetrabromobisphenol (TBBPA) and hexabromocyclododecane (HBCD) in mangrove sediments from the Pearl River Estuary (PRE) in South China were evaluated. Concentrations of TBBPA and HBCD in mangrove sediments ranged from 0.23 to 13.3 and 0.36 to 54.7 ng g−1 dry weight. The highest TBBPA concentration was seen in Guangzhou mangrove wetland near a dockyard and a ferry terminal where TBBPA is utilized in the coatings for the shipbuilding industry. The rapid development of building might elucidate the higher concentrations of HBCD in Shenzhen mangrove sediments. γ-HBCD and α-HBCD was the two main diastereoisomer of HBCD in mangrove sediments with contributions of 56.1 % and 34.0 %. Sediments from the three PRE mangrove ecosystems were selectively enriched for (−)-γ-HBCD. TBBPA concentrations in mangrove sediments from Guangzhou rose during 2012–2015 and declined from 2015 to 2021. HBCD concentrations in the PRE mangrove sediments exhibited an increasing trend from 2012 to 2021.

Highly Diastereoselective Multicomponent Synthesis of Spirocyclopropyl Oxindoles Enabled by Rare-Earth Metal Salts

The synthesis of polysubstituted spirocyclopropyl oxindoles using a series of rare-earth metal (REM) salts is reported. REMs, in particular Sc(OTf)3, allowed access to the target compounds by a multicomponent reaction with high diastereoselectivity (≤94:6:0:0). Density functional theory calculations on the model reaction are consistent with the observed selectivity and revealed that the special coordinating capabilities and the oxophilicity of the metal are key factors in inducing the formation of one main diastereoisomer.

Hexabromocyclododecanes in surface soil-maize system around Baiyangdian Lake in North China: Distribution, enantiomer-specific accumulation, transport, temporal trend and dietary risk

This study investigated the occurrence of hexabromocyclododecanes (HBCDs) in soil-maize system around Baiyangdian Lake. The total concentration of ΣHBCDs was in the order of industrial area > residential area > marginal area > Fuhe River estuary in soil. γ-HBCD was predominated in soils, roots and stems, while α-HBCD was the main diastereoisomer in leaves and kernels. Concentration of ΣHBCDs and three diastereoisomer concentrations in soils were significantly reduced and remained low level from 2018 to 2019. Selectivity enrichment of (+)α- and (-)γ-HBCD was found in soils, roots, stems and leaves, whereas only (+)β-HBCD dominated in stems. Most of the total root bioaccumulation factors (ΣRCFs) were less than 1.0, but no significant correlation was showed between translocation factors (TFs) and log Kow. RCFs and TFs of enantiomers suggested (-)β- and (-)γ-HBCD were easily translocated from soil to roots, while (+)α-, (-)β- and (-)γ-HBCD tended to translocate from stems to leaves. Estimated daily intake (EDI) and of ΣHBCDs, diastereoisomers and enantiomers were all lower than the threshold value, while the Calculated margins of exposure (MOE) were well above the threshold value, which demonstrate the safe consumption of Maize around Baiyangdian Lake.

Levels, distribution and risk assessment of hexabromocyclododecane (HBCD) in fish in Xiamen, China.

In this study, hexabromocyclododecane (HBCD) was detected in 114 fish samples collected from 6 administrative regions of Xiamen city, China. HBCD amounts ranged between ND (not detected) and 2.216ngg-1 ww (mean, 0.127 ± 0.318ngg-1 ww). Besides, α-HBCD was the main diastereoisomer in these fish specimens, followed by β-HBCD. Meanwhile, γ-HBCD was not detected in any of the samples. Significant differences were recorded among fish species. The results indicated that the levels and detection rates of HBCD were higher in Trachinotus ovatus compared with other aquatic organisms. Therefore, Trachinotus ovatus could be used as a marine biological indicator of HBCD. Within the regions investigated, Siming was significantly different from Jimei, Haicang, and Xiang'an. The spatial distribution of HBCD concentrations indicated higher mean levels in samples collected from Haicang, Jimei, and Xiang'an, respectively, with the highest detection rates in Jimei and Xiang'an, which might be related to geographical location and intense industrial and urban activities. Estimation of daily HBCD intake was performed according to fish consumption in Xiamen residents. The medium bound HBCD amounts in fish were approximately 0.073 and 0.088ngkg bw-1d-1 for male and female residents of Xiamen, respectively. Exposure doses of HBCD indicated no health concern for Xiamen residents.

Diastereoselective Synthesis of Axially Chiral Xylose-Derived 1,3-Disubstituted Alkoxyallenes: Scope, Structure, and Mechanism.

The deprotonation of differently substituted propargyl xylosides with s-BuLi/TMEDA followed by protonation with t-butanol at -115 °C provided a range of new axially chiral 1,3-disubstituted alkoxyallenes in a diastereoselective way. Numerous reaction parameters such as solvent, temperature, or protonating agent were examined as well as protecting groups on the xyloside moiety and the influence of the substituents on the alkyne part. The configuration of the main diastereoisomer of 3-methyl-1-xyloside-allene was determined for the first time by single-crystal X-ray diffraction analysis and nOe NMR experiments. Furthermore, DFT calculations on the propargyl/allenyl lithium intermediates formed in the course of the deprotonation reaction provided new structural insights of these complexes. The subsequent protonation process with alcohols was investigated by theoretical surface exploration, revealing the importance of the approach of the alcohol toward the lithium compounds on the reaction outcome.

Metabolites of the anaerobic degradation of diethyl ether by denitrifying betaproteobacterium strain HxN1.

The constitutions of five metabolites formed during co-metabolic, anaerobic degradation of diethyl ether by the denitrifying betaproteobacterium Aromatoleum sp. strain HxN1 were elucidated by comparison of mass spectrometric and gas chromatographic data with those of synthetic reference standards. Furthermore, the absolute configurations of two stereogenic centers in the metabolites were established. Based on these results a degradation pathway for diethyl ether by Aromatoleum sp. HxN1 analogous to that of n-hexane is proposed. Synthesis of both enantiomers of methyl (E)-4-ethoxy-2-pentenoate was accomplished by etherification of ethyl (R)- or (S)-lactate, followed by hydrolysis of the ester group and reduction to furnish 2-ethoxy-1-propanol. The primary alcohol was converted by a Swern oxidation followed by a Horner-Wadsworth-Emmons reaction to methyl (E)-4-ethoxy-2-pentenoate that was finally hydrogenated to methyl 4-ethoxypentanoate. Methyl (S)-4-ethoxy-3-oxopentanoate was prepared by conversion of (S)-2-ethoxypropanoyl chloride with Meldrum's acid. Reduction of the resulting β-oxoester with NaBH4 or baker's yeast gave both diastereoisomers of methyl 4-ethoxy-3-hydroxypentanoate. The stereocenter at C-3 of the main diastereoisomer produced with baker's yeast was determined by Mosher ester analysis to be (R)-configurated. Dimethyl 2-(1-ethoxyethyl)succinate was prepared by Michael addition of nitroethane to diethyl maleate, followed by conjugate addition of sodium ethanolate, hydrolysis and esterification with diazomethane.

Asymmetric Titanium-Catalyzed Cyclopropanation of Nitriles with Grignard Reagents

The titanium-catalyzed asymmetric cyclopropanation of cyanoesters­ with Grignard reagents was investigated for the first time. Particularly, the study of the efficiency of Taddol-based titanium complexes­ has shown that the prior preparation of Taddol titanium complexes was not required and a large panel of ligands was evaluated by using this approach. The spirocyclopropanelactams were obtained with good diastereoselectivity and with moderate enantioselectivities from the main diastereoisomer (up to 32%).

BINOL-Al catalyzed kinetic resolution of citronellal analogues: synthesis of a variety of fragrances

A chiral aluminum catalyst was used for the kinetic resolution of citronellal analogues. Racemic 3-alkylcitronellals gave optically active 5-alkylisopulegols with high enantioselectivity. Unreacted 3-alkylcitronellal analogues were obtained with low enantioselectivity. The two main diastereoisomers of the product were opposite to each other. The scents of 5-substituted isopulegols were evaluated. The chiral recognition of the catalysts and their effects on the kinetic resolutions are also discussed.

Preparation and characterization of α-fluorinated-γ-aminophosphonates

Abstract Herein we would like to present a synthetic approach to series of α-fluorinated-γ-aminophosphonates, which were prepared by hydrogenolysis of (E)-α-fluorovinylphosphonates. The reaction conditions of hydrogenolysis in the presence of palladium on carbon has been optimized. After conversion of aminophosphonates to their oxalte salts, the absolute configuration of the main diastereoisomer has been determined by X-ray analysis. α-Fluorinated-γ-aminophosphonates can be used as convenient precursors (“building blocks”) in the preparation of medicinally important analogues. As an example preparation of dipeptide analogues of α-fluorinated-γ-aminophosphonates was described.

ChemInform Abstract: Stereoselective Epoxidation of Asymmetrized 2-Alkenyl-1,3-propanediols.

Abstract Asymmetrized 2-alkenyl 1,3-propanediols are stereoselectively epoxidized to the same main diastereoisomer both with 3-chloroperbenzoic acid and the VO(acac) 2 /t-butyl hydroperoxyde system. Using the latter epoxidating reagent in combination with a protection-deprotection sequence involving the two homoallylic hydroxy groups, all the four cis epoxides were easily achieved in stereoisomeric pure form starting froma single common ( Z ) precursor.

Toxicokinetics of the Flame Retardant Hexabromocyclododecane Gamma: Effect of Dose, Timing, Route, Repeated Exposure, and Metabolism

Hexabromocyclododecane-gamma (γ-HBCD) is the predominate diastereoisomer in the commercial HBCD mixture used as a flame retardant in a wide variety of consumer products. Three main diastereoisomers, alpha (α), beta (β), and gamma (γ), comprise the mixture. Despite the γ-diastereoisomer being the major diastereoisomer in the mixture and environmental samples, the α-diastereoisomer predominates human tissue and wildlife. This study was conducted to characterize absorption, distribution, metabolism, and excretion parameters of γ-HBCD with respect to dose and time following a single acute exposure and repeated exposure in adult female C57BL/6 mice. Results suggest that 85% of the administered dose (3 mg/kg) was absorbed after po exposure. Disposition was dose independent and did not significantly change after 10 days of exposure. Liver was the major depot (< 0.3% of dose) 4 days after treatment followed by blood, fat, and then brain. γ-HBCD was rapidly metabolized and eliminated in the urine and feces. For the first time, in vivo stereoisomerization was observed of the γ-diastereoisomer to the β-diastereoisomer in liver and brain tissues and to the α- and β-diastereoisomer in fat and feces. Polar metabolites in the blood and urine were a major factor in determining the initial whole-body half-life (1 day) after a single po exposure. Elimination, both whole-body and from individual tissues, was biphasic. Initial half-lives were approximately 1 day, whereas terminal half-lives were up to 4 days, suggesting limited potential for γ-diastereoisomer bioaccumulation. The toxicokinetic behavior reported here has important implications for the extrapolation of toxicological studies of the commercial HBCD mixture to the assessment of risk.

Identification of the Novel Cycloaliphatic Brominated Flame Retardant 1,2-Dibromo-4-(1,2-dibromoethyl)cyclohexane in Canadian Arctic Beluga (Delphinapterus leucas)

1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (TBECH) is used primarily as an additive flame retardant. Technical grade TBECH consists of near equimolar amounts of two (of a possible four) diastereoisomers: rac-(1R,2R)-1,2-dibromo-(4S)-4-((1S)-1,2-dibromoethyl)cyclohexane ((alpha-TBECH) and rac-(1R,2R)-1,2-dibromo-(4S)-4-((1R)-1,2-dibromoethyl)cyclohexane (beta-TBECH). The two other possible isomers, gamma- and delta-TBECH, appear in the technical mixture when heated at temperatures above 120 degrees C. Careful selection of GC-capillary column length was critical in resolution of the two main diastereoisomers. Column lengths of 60 or 30 m (0.25 microm film thickness) resulted in incomplete separation of the alpha- and beta-isomers, while on a 10 m column, the isomers were baseline separated. The gamma- and delta-isomers could not be resolved on any column length in this study. Increased injector port temperature induced thermal conversion of the alpha- and beta-isomers to gamma- and delta-TBECH. Electron impact ionization (EI) was used to provide specificity because no characteristic ions in the electron capture negative ionization (ECNI) mass spectrum of TBECH were evident. In EI, the dominant ions in the mass spectrum corresponded to a concomitant loss of HBr and Br from the molecular ion; the biggest peak in this ion cluster (m/z 266.9208) was used for quantitation and the second biggest peak (m/z 264.9227) was used for confirmation. Beluga (Delphinapterus leucas) blubber extracts of animals from the Canadian Arctic (n=29) were analyzed using low resolution (LR) MS and high resolution (HR) MS run at a resolving power of 10,000. beta-TBECH was the only isomer observed in the samples and was detected in 17 samples. The LRMS technique appeared to overestimate beta-TBECH concentrations compared to HRMS, suggesting a small interference arose at the nominal mass monitored. This potential interference also led to some false positive and negative values (n=7) based on the expected ion ratio of the quantitation and confirmation ions. Observed concentrations of the beta-isomer as measured by HRMS ranged from 1.1 to 9.3 ng/g (lipid weight).

Theoretical Prediction of the p53 Gene Mutagenic Mechanism Induced bytrans-4-Hydroxy-2-nonenal

The reaction mechanism of guanine with trans-4-hydroxyl-2-nonenal (4-HNE) and the mutagenic mechanism induced by adducts have been theoretically predicted at a molecular level from the energy point of view. 4-HNE directly reacts with guanine via three steps, yielding eventually four main diastereoisomers: trans-4-HNE-dG adducts. A concerted six-atom-centered transition state is proposed for the first step, while the last two steps are involved in four-membered-ring transition states. The third step is the rate-determining step. The studies of base pairing properties of trans-4-HNE-dG adducts with A, T, C, A*, and T* together with the relationship between the mutation and structure of trans-4-HNE-dG indicate that syn- and anti-conformations of trans-4-HNE-dG around the glycosidic bond are favorable for pairing with A* and T*, respectively, in the parental generation. As a result, the GC --> CG or GC --> TA mutation may be generated from the syn-4-HNE-dGA* during replication. Nevertheless, anti-4-HNE-dGT* creates GC --> TA mutation or nonmutagenesis. Moreover, syn-4-HNE-dGA* has a slightly higher probability to be generated than anti-4-HNE-dGT* in the parental generation; therefore, the GC to TA transversion is predominant among the mutations. In addition, no correlation between the mutations and the stereochemistry of C6 and C8 of trans-4-HNE-dG adducts was found in this work. Our mutational results have interpreted well a part of the discrete experimental observations, but the mutagenic process itself has not previously been characterized, through either computation or experiment.

Diastereoselective Synthesis of Tetrahydrofurans via Reaction of γ,δ‐Epoxycarbanions with Aldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Diastereoselective Synthesis of Tetrahydrofurans via Reaction of γ,δ-Epoxycarbanions with Aldehydes

[reaction: see text] Hydroxymethyl-substituted tetrahydrofurans were prepared with high diastereoselectivity by reaction of the carbanion derived from 3,4-epoxybutyl phenyl sulfone with aldehydes in the presence of a mixture of lithium and potassium tert-butoxides. Initial formation of aldol-type adducts is a nondiastereoselective but reversible process; thus, subsequent formation of one main diastereoisomer is controlled by the relative rates of cyclization. The configuration of the carbon stereocenter at the oxirane ring is inverted in the course of the S(N)2 process, and two new centers are created diastereoselectively.

Stereoselective synthesis of β-amino-γ-butyrolactones

A novel synthesis of optically active β-amino-γ-butyrolactones is described. O-Silylated ( R)-cyanohydrins ( R)- 3 (derived from aldehydes 1 by ( R)-hydroxynitrile lyase (( R)-PaHNL)-catalyzed addition of HCN) were reacted with allyl Grignard to give amino alcohols (4 R,5 S)- 5 after reduction. In the addition of crotyl Grignard reagent, workup conditions are decisive for the formation of amino alcohol 8, which was isolated as a diastereoisomeric mixture; the acetylated main diastereoisomer (3 S,4 R,5 R)- 10 was separated. Ozonolysis of the acetylated amino alcohols (4 S,5 R)- 7a, b and (3 S,4 S,5 R)- 10 affords the aldehydes 12a– c, which were directly oxidized with CrO 3 in dilute H 2SO 4 to yield the β-acetamido-γ-acetoxycarboxylic acids (3 S,4 R)- 13a, b and (2 R,3 S,4 R)- 13c. Compounds 13 cyclized spontaneously under acidic conditions to afford β-acetamido-γ-butyrolactones (4 S,5 R)- 14a, b and (3 R,4 S,5 R)- 14c.

( R)- and ( S)-3-Hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone as chiral auxiliaries in the enantioselective preparation of α-amino acids

rac-α-Amino acids ( rac- 1a– d) were formally deracemized by a four-step reaction sequence: (a) protection of the amino function as the phthalimido derivative; (b) acyl chloride formation; (c) diastereoselective reaction with the chiral auxiliaries ( R)- or ( S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone, ( R)- or ( S)- 3; and (d) acid hydrolysis to deprotect both the ester and phthalimido functions. Diastereoselectivities of the intermediate esters 4 were good (82–96% d.e.), except for the case of 4b (41% d.e.), the precursor of valine. The main diastereoisomer of esters 4 was (α R,3 S)- or (α S,3 R)-, except for 4d: in this case, working at −78°C, the (α R,3 R)-diastereoisomer was the main product, which epimerizes easily at the α-position when at room temperature. Acid hydrolysis of esters 4 directly gave the deprotected α-amino acids, with little or no epimerization at the α-position of the α-amino acid and complete recovery of the chiral auxiliary. Only (α R,3 R)- 4d on acid hydrolysis partially epimerized at the α-position. Moreover, some α-amino acids and their N, N-dibenzyl derivatives were obtained by dynamic kinetic resolution of diastereoisomeric mixtures of α-bromo esters 5 derived from the chiral auxiliaries ( R)- or ( S)- 3 during reaction with dibenzylamine.

Stereoselectivity in Reactions of 1,2-Dioxy-Substituted Radicals under Chelation Control: An Unexpected Result

The strong pyramidalization of the radical intermediates (shown on the right) is the reason why anti Cram chelation products are obtained in the reduction of 1,2-dialkyl-1,2-dioxy-substituted radicals, even though a chelate is formed. The main diastereoisomer results from an attack syn to the large substituent R2. R1  CH2CHCHCH2SnBu3, R2  tBu, R  para-methoxyphenyl.

Repair of the two diastereoisomer photoadducts formed between 7-methylpyrido(3,4-c)psoralen (MePyPs) and thymidine in yeast cells: A chemical approach

When analysing the repair of psoralen plus UVA-induced photoadducts in DNA, it must be realized that, in most cases, different isomers are formed. The monofunctional psoralen derivative 7-methylpyrido(3,4-c)psoralen (MePyPs) is known for its high antiproliferative activity at the cellular level and interesting photochemotherapeutic properties. To understand its photobiological efficiency in more detail, the induction of specific photoadducts in DNA and their repair were analysed in a eukaryotic cell system, the yeast Saccharomyces cerevisiae. After photoaddition of MePyPs, two main diastereoisomers were characterized after enzymatic hydrolysis of the DNA and analysis by high performance liquid chromatography. One diastereoisomer was more effectively repaired in yeast than the other during post-treatment incubation, suggesting that the two diastereoisomers may be recognized differently by cellular enzymatic repair systems.

Stereoselective epoxidation of asymmetrized 2-alkenyl-1,3-propanediols.

Asymmetrized 2-alkenyl 1,3-propanediols are stereoselectively epoxidized to the same main diastereoisomer both with 3-chloroperbenzoic acid and the VO(acac) 2/t-butyl hydroperoxyde system. Using the latter epoxidating reagent in combination with a protection-deprotection sequence involving the two homoallylic hydroxy groups, all the four cis epoxides were easily achieved in stereoisomeric pure form starting froma single common ( Z) precursor.