Mass Spectra of Volatile Sulfur Compounds in Foods

The absolute configurations of twelve α-aryl and α,β-diarylalkylamines were studied as N-acyl derivatives by circular dichroism (CD) measurements and by gas chromatography (GC).

The signs of Cotton effects for the S-configuration around 260 nm were positive and those around 210 nm were negative, although some exceptions were found due to the substituents on the benzene nuclei. In contrast, the GC behavior was considered less sensitive to the substituents on the benzene nuclei, and the elution orders were an R-before S-configuration consistently on a chiral OA-300 column. The absolute configurations of some amines were estimated in this study. GC as well as CD measurements could be a promising method for the assignment of the absolute configuration.     

Enantioselective σ1 receptor binding and biotransformation of the spirocyclic PET tracer 1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine]

It was shown that racemic (±)‐ 2 [1′‐benzyl‐3‐(3‐fluoropropyl)‐3H‐spiro[[2]benzofuran‐1,4′‐piperidine], WMS‐1813 ] represents a promising positron emission tomography (PET) tracer for the investigation of centrally located σ₁ receptors. To study the pharmacological activity of the enantiomers of 2 , a preparative HPLC separation of (R)‐2 and (S)‐2 was performed. The absolute configuration of the enantiomers was determined by CD‐spectroscopy together with theoretical calculations of the CD‐spectrum of a model compound. In receptor binding studies with the radioligand [³H]‐(+)‐pentazocine, (S)‐2 was thrice more potent than its (R)‐configured enantiomer (R)‐2 . The metabolic degradation of the more potent (S)‐enantiomer was considerably slower than the metabolism of (R)‐2 . The structures of the main metabolites of both enantiomers were elucidated by determination of the exact mass using an Orbitrap‐LC‐MS system. These experiments showed a stereoselective biotransformation of the enantiomers of 2 . Chirality, 2011. © 2010 Wiley‐Liss, Inc.     

Assignment of absolute configuration to an improved enantioselective naproxen selector

Assignment of absolute configuration to a recently developed chiral selector useful in the separation of the underivatized enantiomers of naproxen and other nonsteroidal anti-inflammatory drugs (NSAIDs) is described. Circular dichroism, ¹H NMR, and X-ray diffraction have been used to confirm the original assignment which was based solely upon elution orders from HPLC chiral stationary phases. All of these techniques agree in the assignment of the (S,S) absolute configuration to the enantiomer of the chiral selector which associates preferentially with (S)-naproxen. © 1994 Wiley-Liss, Inc.     

Determination of pindolol enantiomers in human plasma and urine by simple liquid–liquid extraction and high-performance liquid chromatography

A simple method for the measurement of pindolol enantiomers by HPLC is presented. Alkalinized serum or urine is extracted with ethyl acetate and the residue remaining after evaporation of the organic layer is then derivatised with (S)-(−)-α-methylbenzyl isocyanate. The diastereoisomers of derivatised pindolol and metoprolol (internal standard) are separated by high-performance liquid chromatography (HPLC) using a C₁₈ silica column and detected using fluorescence (excitation λ: 215 nm, emission λ: 320 nm). The assay displays reproducible linearity for pindolol enantiomers with a correlation coefficient of r²≥0.998 over the concentration range 8–100 ng ml⁻¹ for plasma and 0.1–2.5 μg ml⁻¹ for urine. The coefficient of variation for accuracy and precision of the quality control samples for both plasma and urine are consistently <10%. Assay parameters are similar to those of previously published assays for pindolol enantiomers, however this assay is significantly easier and cheaper to run. Clinically relevant concentrations of each pindolol enantiomer can readily be measured.     

Metabolism of Chiral Ionylideneacetic Acids on the Abscisic Acid Biosynthetic Pathway in Cercospora

A Chiralcel OJ column was used to determine the absolute configuration of naturally occurring α-ionylideneacetic acid from Cercospora rosicola and γ-ionylideneacetic acid from C. cruenta as (R) enantiomers in accordance with their biosynthetic product, (S)-ABA. Both enantiomers of [1, 2-¹³C₂]-α and γ-ionylideneacetic acids were prepared and fed to C. rosicola and C. cruenta. Six combinations of feeding experiments comparatively and unequivocally demonstrated stereoselectivity in the biosynthetic conversions, including stepwise hydroxylation at C-1′ and 4′. Enzymatic isomerization from the γ to α-intermediate was suggested not to be involved in ABA biosynthesis in C. rosicola.     

A Forgotten Chiral Spiro Compound Revisited: 3,3'‐Dimethyl‐3H,3'H‐2,2'‐spirobi[[1,3]benzothiazole]

The title compound was obtained as a side product during dimerization‐oxidation steps of the carbene generated from N‐methylbenzothiazolium iodide. Chromatography on (S,S)‐Whelk O1 column showed on cooling a typical plateau shape chromatogram indicating an exchange between two enantiomers on the column. The thermal barrier to racemization was determined (85 kJ.mol^?1 at 10 °C) by dynamic high‐performance liquid chromatography (DHPLC).The absolute configuration of the first (M) and second eluted (P) enantiomers on the (S, S)‐Whelk O1 column was established by comparing the reconstructed circular dichroism (CD) spectra from the CD detector signal and the calculated CD spectrum of the (P) enantiomer. Mass spectrometry revealed that 3,3'‐dimethyl‐3H,3'H‐2,2'‐spirobi[[1,3]benzothiazole] can be viewed as a masked thiophenate attached to a benzothiazolium framework. Chirality 27:716–721, 2015. © 2015 Wiley Periodicals, Inc.     

Eudistomidin G,a new β-carboline alkaloid from the Okinawan marine tunicate Eudistoma glaucus and structure revision of eudistomidin B

A new β-carboline alkaloid, eudistomidin G (1), has been isolated from the Okinawan marine tunicate Eudistoma glaucus, and the structure was elucidated from spectroscopic data. Furthermore, the structure of eudistomidin B (2), which has been isolated from the same tunicate, was revised from 2a to 2b by detailed analyses of spectroscopic data. Asymmetric synthesis of the revised structure (2b) of eudistomidin B (2) and its (1S,10S)-diastereomer (2c) has been accomplished with the Noyori catalytic asymmetric hydrogen-transfer reaction. The absolute configuration of eudistomidin B (2) was confirmed to be 2b possessing (1R,10S)-configuration, from comparison of the ¹H NMR data, CD spectra, [α]_D values, and HPLC analysis of 2b, 2c, and natural eudistomidin B.     

Stereoselective metabolism of propranolol glucuronidation by human UDP‐glucuronosyltransferases 2B7 and 1A9

Stereoselective metabolism of propranolol side‐chain glucuronidation was studied for two recombinant human uridine diphosphate glucuronosyltransferases (UGTs), UGT1A9 and UGT2B7. The S‐ and R‐propranolol side‐chain glucuronides produced in the incubation mixtures were assayed simultaneously by RP‐HPLC with fluorescent detector. The excitation and emission wavelengths were set at 310 nm and 339 nm, respectively. UGT1A9 prefers catalyzing S‐enantiomer to R‐enantiomer and the intrinsic clearance (CL_int) ratios of S‐enantiomer to R‐enantiomer are 3.8 times and 6.5times for racemic propranolol and individual enantiomers, respectively. UGT2B7, however, catalyzes slightly less S‐enantiomer than R‐enantiomer and the CL_int ratio of S‐enantiomer to R‐enantiomer is 0.8 times. The high concentration of racemic propranolol (>0.57 mmol/l) and individual enantiomers (>0.69 mmol/l) exhibited substrate inhibition of glucuronidation for UGT2B7, but only the S‐enantiomer (>0.44 mmol/l) in racemic propranolol exhibited substrate inhibition for UGT1A9. The substrate inhibition constants (K_si) were all similar (P > 0.05). Drug–drug interactions were also found between S‐ and R‐enantiomer glucuronidation metabolisms by UGT1A9 and UGT2B7. Chirality 2010. © 2009 Wiley‐Liss, Inc.     

Use of lipases in the resolution of racemic ibuprofen

Summary Resolution of (R,S)-ibuprofen enantiomers by esterification in different organic solvents was studied using Candida cylindracea lipase. This enzyme preparation had high enantiospecificity for S(+)-ibuprofen in the esterification reaction of a racemic ibuprofen with primary alcohols. The esterification yields of secondary alcohols were much lower than those of primary alcohols. Esterification with tertiary alcohols was not observed. The synthesis of esters was profoundly affected by the amount of water in the reaction mixture. C. cylindracea lipase was active only in very hydrophobic solvents. The esterification activity of the lipase was reduced significantly by addition of water. The R- and S-enantiomers of ibuprofen were determined without derivatization by HPLC using a chiral column.     

Spectroscopic Studies on Nicotine and Nornicotine in the UV Region

The UV absorption and electronic circular dichroism (ECD) spectra of (R)‐ and (S)‐nicotine and (S)‐nornicotine in aqueous solution were measured to a significantly lower wavelength range than previously reported, allowing the identification of four previously unobserved electronic transitions. The ECD spectra of the two enantiomers of nicotine were equal in magnitude and opposite in sign, while the UV absorption spectra were coincidental. In line with previous observations, (S)‐nicotine exhibited a negative cotton effect centered on 263 nm with vibronic structure (π–π₁* transition) and a broad, positive ECD signal at around 240 nm associated with the n–π₁* transition. As expected this band disappeared when the pyridyl aromatic moiety was protonated. Four further electronic transitions are reported between 215 and 180 nm; it is proposed the negative maxima around 206 nm is either an n–σ* transition or a charge transfer band resulting from the movement of charge from the pyrrolidyl N lone pair to the pyridyl π* orbital. The pyridyl π–π₂* transition may be contained within the negative ECD signal envelope at around 200 nm. Another negative maximum at 188 nm is thought to be the pyridyl π–π₃* transition, while the lowest wavelength end‐absorption and positive ECD may be associated with the π–π₄* transition. The UV absorption spectra of (S)‐nornicotine was similar to that of (S)‐nicotine in the range 280–220 nm and acidification of the aqueous solution enhanced the absorption. The ECD signals of (S)‐nornicotine were considerably less intense compared to (S)‐nicotine and declined further on acidification; in the far UV region the ECD spectra diverge considerably. Chirality 25:288–293, 2013. © 2013 Wiley Periodicals, Inc.     

Stereoselective Binding of Flurbiprofen Enantiomers and their Methyl Esters to Human Serum Albumin Studied by Time-Resolved Phosphorescence

The interaction of the nonsteroidal anti‐inflammatory drug flurbiprofen (FBP) with human serum albumin (HSA) hardly influences the fluorescence of the protein's single tryptophan (Trp). Therefore, in addition to fluorescence, heavy atom‐induced room‐temperature phosphorescence is used to study the stereoselective binding of FBP enantiomers and their methyl esters to HSA. Maximal HSA phosphorescence intensities were obtained at a KI concentration of 0.2 M. The quenching of the Trp phosphorescence by FBP is mainly dynamic and based on Dexter energy transfer. The Stern–Volmer plots based on the phosphorescence lifetimes indicate that (R)‐FBP causes a stronger Trp quenching than (S)‐FBP. For the methyl esters of FBP, the opposite is observed: (S)‐(FBPMe) quenches more than (R)‐FBPMe. The Stern–Volmer plots of (R)‐FBP and (R)‐FBPMe are similar although their high‐affinity binding sites are different. The methylation of (S)‐FBP causes a large change in its effect on the HSA phosphorescence lifetime. Furthermore, the quenching constants of 3.0 × 10⁷ M^?1 s^?1 of the R‐enantiomers and 2.5 × 10⁷ M^?1 s^?1 for the S‐enantiomers are not influenced by the methylation and indicate a stereoselectivity in the accessibility of the HSA Trp to these drugs. Chirality 24:840–846, 2012. © 2012 Wiley Periodicals, Inc.     

Tetrathiafulvalene‐[2.2]paracyclophanes: Synthesis,crystal structures,and chiroptical properties

Two racemic tetrathiafulvalene‐[2.2]paracyclophane electron donors EDT‐TTF‐[2.2]paracyclophane 1 and (COOMe)₂‐TTF‐[2.2]paracyclophane 2 have been synthesized via the phosphite mediated cross coupling strategy. Chiral HPLC allowed the optical resolution of the (R_P) and (S_P) enantiomers for both compounds. Solid‐state structures of (R_P)‐ 1 and (rac)‐ 2 have been determined by single crystal X‐ray analysis. Intermolecular π‐π and S???S interactions are disclosed in the packing. Single crystal X‐ray analysis of (R_P)‐ 1 combined with experimental and theoretical circular dichroism spectra allowed the assignment of the absolute configuration of the enantiomers of 1 and 2 .     

Biotransformations of 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid and the determination of the absolute configuration of all isomers

2-Hydroxy-2-(ethoxyphenylphosphinyl)acetic acid, a new type of organophosphorus compound possessing two stereogenic centers, was investigated. Racemic 2-butyryloxy-2-(ethoxyphenylphosphinyl)acetic acid was synthesized and hydrolyzed using four bacterial species as biocatalysts. In all cases the reaction was more or less stereoselective and isomers bearing a phosphorus atom with an (S_P)-configuration were hydrolyzed preferentially. The observed ¹H and ³¹P NMR chemical shifts of Mosher esters of 2-hydroxy-2-(ethoxyphenylphosphinyl)acetic acid were correlated with the configurations of both stereogenic centers of all four stereoisomers.     

Absolute configuration and stereochemical analysis of 3α,6β-dibenzoyloxytropane

Both enantiomers of 3α,6β-dibenzoyloxytropane (1) have been prepared from optical active 6β-hydroxyhyoscyamines establishing their absolute configurations as (?)-(3R,6R) and (+)-(3S,6S)-dibenzoyloxytropane. Independent stereochemical confirmation was obtained by vibrational circular dichroism measurements, since bands characteristic of (3R,6R) and (3S,6S) configurations of tropanediols derivatives were observed. In addition, a chiral HPLC method was developed for determining absolute configurations of tropane-related natural substances at the microgram (μg) level. The complete ¹H NMR characterization of the scaffold of 1 is also reported.     

Circular dichroism of axially chiral methaqualone, 3-Aryl-2-mercapto- and 3-aryl-2-alkylthio-4(3H)-quinazolinones: conformational dependence of CD and assignment of absolute configuration

Rotational strengths calculated on the basis of quantum-mechanically obtained minimum energy geometries were used to determine the absolute configurations of axially chiral 3-aryl-4(3H)-quinazolinones from the sign of the observed Cotton effects (CEs). For the spectral data, CNDO/S calculations were used; for the geometries, ab initio (RHF/6-31G) and semiempirical (AM1) theories were used. Oscillator and rotational strengths of all excited states down to 200 nm were compared to experimental absorption and circular dichroism (CD) data. It was found that the sign of the ¹L_b Cotton effects obtained for the enantiomers of methaqualone and derivatives of 3-aryl-2-alkylthio-4(3H)-quinazolinones can be correlated unambiguously with the absolute configuration. Furthermore, the sign of the Cotton effect of the π-π* transition of the thiocarbonyl chromophore of 3-aryl-2-mercapto-4(3H)-quinazolinones is suitable for a successful stereochemical correlation. Chirality 10:253–261, 1998. © 1998 Wiley-Liss, Inc.     

Reduction by a model of NAD(P)H: XI. Stereochemistry of a lactate dehydrogenase-model reaction

Stereochemistry of the biomimetic reduction of α-keto esters with NAD(P)H-model compounds has been investigated. The model compound with the R-configuration reduces the α-keto esters to the (R)-α-hydroxy esters, whereas (S)-α-hydroxy esters are afforded by the reduction with the S-configurational model compounds. It has been concluded that pro-R and -S hydrogens of the model compounds with R- and S-configuration, respectively, contribute predominantly to the reduction.     

The determination of enantiomer composition of 1‐((3‐chlorophenyl)‐(phenyl)methyl) amine and 1‐((3‐chlorophenyl)(phenyl)‐methyl) urea (Galodif) by NMR spectroscopy,chiral HPLC,and polarimetry

For the first time, a method for enantiomer resolution of the anticonvulsant Galodif (1‐((3‐chlorophenyl)(phenyl)methyl) urea) by chiral HPLC was developed, whereas the enantiomeric composition of 1‐((3‐chlorophenyl)(phenyl)methyl) amine—precursor in Galodif synthesis—cannot be resolved by this method. However, starting 1‐((3‐chlorophenyl)(phenyl)methyl) amine quantitatively forms diastereomeric N‐((3‐chlorophenyl)(phenyl)methyl)‐1‐camphorsulfonamides in reaction with chiral (1R)‐(+)‐ or (1S)‐(?)‐camphor‐10‐sulfonyl chlorides. The diastereomeric ratio of obtained camphorsulfonamides can be easily determined by NMR ¹H and ¹³C spectroscopy. The DFT calculations of specific rotation of Galodif enantiomers showed good agreement with experimental data. The absolute configuration of enantiomers was proposed for the first time.     

Enantioselective Acute Toxicity Effects and Bioaccumulation of Furalaxyl in the Earthworm (Eisenia foetida)

The enantioselectivities of individual enantiomers of furalaxyl in acute toxicity and bioaccumulation in the earthworm (Eisenia foetida) were studied. The acute toxicity was tested by filter paper contact test. After 48 h of exposure, the calculated LC₅₀ values of the R‐form, rac‐form, and S‐form were 2.27, 2.08, and 1.22 µg cm^‐2, respectively. After 72 h of exposure, the calculated LC₅₀ values were 1.90, 1.54, and 1.00 µg cm^‐2, respectively. Therefore, the acute toxicity of furalaxyl enantiomers was enantioselective. During the bioaccumulation experiment, the enantiomer fraction of furalaxyl in earthworm tissue was observed to deviate from 0.50 and maintained a range of 0.55–0.60; in other words, the bioaccumulation of furalaxyl was enantioselective in earthworm tissue with a preferential accumulation of S‐furalaxyl. The uptake kinetic of furalaxyl enantiomers fitted the first‐order kinetics well and the calculated kinetic parameters were consistent with the low accumulation efficiency. Chirality 26:307–312, 2014. © 2014 Wiley Periodicals, Inc.     

Influence of Gasoline Inhalation on the Enantioselective Pharmacokinetics of Fluoxetine in Rats

Fluoxetine is used clinically as a racemic mixture of (+)‐(S) and (–)‐(R) enantiomers for the treatment of depression. CYP2D6 catalyzes the metabolism of both fluoxetine enantiomers. We aimed to evaluate whether exposure to gasoline results in CYP2D inhibition. Male Wistar rats exposed to filtered air (n = 36; control group) or to 600 ppm of gasoline (n = 36) in a nose‐only inhalation exposure chamber for 6 weeks (6 h/day, 5 days/week) received a single oral 10‐mg/kg dose of racemic fluoxetine. Fluoxetine enantiomers in plasma samples were analyzed by a validated analytical method using LC‐MS/MS. The separation of fluoxetine enantiomers was performed in a Chirobiotic V column using as the mobile phase a mixture of ethanol:ammonium acetate 15 mM. Higher plasma concentrations of the (+)‐(S)‐fluoxetine enantiomer were found in the control group (enantiomeric ratio AUC_{(+)‐(S)/(–)‐(R)} = 1.68). In animals exposed to gasoline, we observed an increase in AUC_0‐∞ for both enantiomers, with a sharper increase seen for the (–)‐(R)‐fluoxetine enantiomer (enantiomeric ratio AUC_{(+)‐(S)/(–)‐(R)} = 1.07), resulting in a loss of enantioselectivity. Exposure to gasoline was found to result in the loss of enantioselectivity of fluoxetine, with the predominant reduction occurring in the clearance of the (–)‐(R)‐fluoxetine enantiomer (55% vs. 30%). Chirality 25:206–210, 2013. © 2013 Wiley Periodicals, Inc.     

Preparation of Single-Enantiomer Biofunctional Molecules with (S)-2-Methoxy-2-(1-naphthyl)propanoic Acid

(RS)-β-Ionol and (RS)-2-methyl-4-octanol were resolved by using (S)-2-methoxy-2-(1-naphthyl)propanoic acid [(S)-MαNP acid]. The specific stereochemistry of each MαNP ester was elucidated by 2D NMR analyses, and shielding by the 1-naphthyl group was observed in both the ¹H- and ¹³C-NMR spectra. Solvolysis of the individual (S)-MαNP esters gave four single-enantiomer alcohols. The normal-phase HPLC elution order of each MαNP ester is also discussed.