Stereochemical analysis of d-galacto-sulfoxides using (S)-α-methoxyphenylacetic acid

Buist, Peter H.; Behrouzian, Behnaz; Cassel, Stéphanie; Lorin, C.; Rollin, Patrick; Pérez, Serge

doi:10.1016/s0957-4166(97)00207-3

Cited by 11 publications

(3 citation statements)

References 4 publications

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“…From these two experiments, it was concluded that H1 and H2 protons were involved in intermolecular and intramolecular H‐bonding, respectively. However, as reported by Buist et al,19, 25 the direct hydrogen bonding between OH group of MPA and oxygen atom of the sulfoxide were not observed in the present investigation. Figure 1 shows the intramolecular and intermolecular hydrogen bonding interactions formed between R ‐MPA and rac‐MDL.…”

Section: Resultscontrasting

confidence: 47%

Evaluation of (R)‐(−)‐α‐methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by ¹H NMR spectroscopy

2012

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(R)-(-)-α-Methoxy phenyl acetic acid, (S)-(-)-1,1'-(2-naphthol), and (R)-(+)-α-methoxy-α-trifluoromethyl phenyl acetic acid were evaluated as chiral shift reagents (CSRs) for (1)H NMR spectroscopic resolution and determination of R and S enantiomers of modafinil (MDL) in bulk drugs and formulations. Effects of the nature of CSR and the weight ratio of substrate to shift reagent on enantiomeric discrimination were investigated. Intramolecular and intermolecular hydrogen bonding interactions between the drug and the CSR seem to be the driving force for desired resolution. A mechanism was proposed to explain the interactions between (R, S)-enantiomers of MDL and (R)-(-)-α-methoxy phenyl acetic acid. The method was validated and applied successfully to determine the enantiomeric purity of MDL in tablet formulations.

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Section: Resultscontrasting

confidence: 47%

Evaluation of (R)‐(−)‐α‐methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by ¹H NMR spectroscopy

2012

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“…The enantiomeric purity and absolute configuration of biosynthetic methyl 6-thiaoleate S -oxide was assessed through the use of a chiral NMR shift reagent, ( S )-α-methoxyphenylacetic acid, ( S )-MPAA . According to the model that we have validated, , interaction of ( S )- 6 with this reagent should lead to an upfield shift of the 1 H NMR signals of the methylene group at C-2 relative to the corresponding signals of the corresponding ( R )-sulfoxide (Figure ). The C-2 triplet was used as a reporter group since the 1 H NMR signals of the other methylene groups were either too complex to analyze unambiguously or overlapped with signals from the thialinoleyl byproduct…”

Section: Resultsmentioning

confidence: 99%

γ-Linolenic Acid Biosynthesis: Cryptoregiochemistry of Δ⁶ Desaturation

Fauconnot

Buist²

2001

J. Org. Chem.

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The valuable nutraceutical gamma-linolenic acid (GLA, (6Z,9Z,12Z)-octadecatrienoic acid) is biosynthesized by a series of regio- and stereoselective dehydrogenation reactions that are catalyzed by a set of enzymes known as fatty acid desaturases. As part of ongoing research into the mechanism of these remarkable catalysts, we have examined the cryptoregiochemistry (site of initial oxidation) of Delta6 desaturation as it occurs in the protozoan Tetrahymena thermophila. Two complementary approaches that address this issue are described. In the first set of experiments, we measured the individual primary deuterium kinetic isotope effects associated with the C-H bond cleavages at C-6 and C-7. Competition experiments using appropriately deuterium-labeled 4-thiasubstrates revealed that a large KIE (kH/kD = 7.1 +/- 0.5) was observed for the C-H bond-breaking step at C-6, whereas the C-H bond cleavage at C-7 was insensitive to deuterium substitution (kH/kD = 1.04 +/- 0.05). These results point to C-6 as the site of initial oxidation in Delta6 desaturation since the first chemical step in this type of reaction is rupture of a strong, unactivated C-H bond, an energetically difficult process that typically exhibits a large KIE. This conclusion was supported by the results of our second approach, which involved locating the position of the putative diiron oxo oxidant with respect to substrate by monitoring the efficiency of oxo transfer to a series of thia fatty acid probes. Thus only a 6-thia-analogue is converted to significant amounts of the corresponding sulfoxide (9% yield). The absolute configuration of this product was determined to be S using (S)-MPAA as a chiral shift reagent. Taken together, these results point to the abstraction of the C-6 pro S hydrogen as the initial event in Delta6 desaturation as it occurs in T. thermophila.

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“…This model is consistent with the experimental data reported [14,15] where, in every instance, the sense of nonequivalence of the two groups on either side of sulfur are opposite and correlated to the sulfoxide AC. The same authors also showed that acid (S)-6 can be conveniently used for AC assignment of aryl and benzyl sulfoxides like 7e-g, and 8a-c [20], as well as complex galacto-sulfoxides [21], whose AC assignment was also subsequently confirmed by X-ray analysis [22]. (1)) was later used by Kagan and coworkers [16] to determine the enantiomeric purities of chiral sulfoxides obtained by enantioselective oxidation of sulfides [6c,d].…”

Section: Nmr Spectroscopymentioning

confidence: 99%

Recent Progress in Application of Spectroscopic Methods for Assigning Absolute Configuration of Optically Active Sulfoxides

Donnoli¹,

Superchi²,

Rosini

2006

MROC

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In the recent years, in addition to the more traditional methods based on X-ray diffraction and mechanistic considerations, the problem of the configurational assignment of optically active sulfoxides has been approached with spectroscopic methods. In this review the methods based on the use of NMR spectroscopy and electronic circular dichroism are described, as well as the emerging approaches based on the analysis of vibrational CD spectra, on the ab initio calculation of the optical rotation and on the cholesteric induction in nematic solvents. The advantage and limitations of each approach are discussed with a major attention to their reliability and practicality.

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Stereochemical analysis of d-galacto-sulfoxides using (S)-α-methoxyphenylacetic acid

Cited by 11 publications

References 4 publications

Evaluation of (R)‐(−)‐α‐methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by ¹H NMR spectroscopy

Evaluation of (R)‐(−)‐α‐methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by ¹H NMR spectroscopy

γ-Linolenic Acid Biosynthesis: Cryptoregiochemistry of Δ⁶ Desaturation

Recent Progress in Application of Spectroscopic Methods for Assigning Absolute Configuration of Optically Active Sulfoxides

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Stereochemical analysis of d-galacto-sulfoxides using (S)-α-methoxyphenylacetic acid

Cited by 11 publications

References 4 publications

Evaluation of (R)‐(−)‐α‐methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by 1H NMR spectroscopy

Evaluation of (R)‐(−)‐α‐methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by 1H NMR spectroscopy

γ-Linolenic Acid Biosynthesis: Cryptoregiochemistry of Δ6 Desaturation

Recent Progress in Application of Spectroscopic Methods for Assigning Absolute Configuration of Optically Active Sulfoxides

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Product

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Evaluation of (R)‐(−)‐α‐methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by ¹H NMR spectroscopy

Evaluation of (R)‐(−)‐α‐methoxy phenyl acetic acid as a chiral shift reagent for resolution and determination of R and S enantiomers of modafinil in bulk drugs and formulations by ¹H NMR spectroscopy

γ-Linolenic Acid Biosynthesis: Cryptoregiochemistry of Δ⁶ Desaturation