First Total Synthesis of Phytoprostanes with Prostaglandin‐Like Configuration, Evidence for Their Formation in Edible Vegetable Oils and Orienting Study of Their Biological Activity

Smrček, Jakub; Hájek, Miroslav; Hodek, Ondřej; Čížek, Karel; Pohl, Radek; Jahn, Emanuela; Galano, Jean‐Marie; Oger, Camille; Cvačka, Josef; Jahn, Ullrich

doi:10.1002/chem.202100872

Cited by 5 publications

(4 citation statements)

References 76 publications

(146 reference statements)

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“…A total of 67 species were included in the method, of which 62 could be obtained as isolated pure standards. PhytoPs and PhytoFs were only included in the LC method because they possess multiple chiral centers in combination with multiple double bond configurations, the resolution of which would lead to complex chromatography . Additionally, because PhytoPs and PhytoFs are produced by autoxidation (Figure S2), the ensuing signal splitting of the racemates would result in sensitivity decrease.…”

Section: Resultsmentioning

confidence: 99%

Development of a Chiral Supercritical Fluid Chromatography–Tandem Mass Spectrometry and Reversed-Phase Liquid Chromatography–Tandem Mass Spectrometry Platform for the Quantitative Metabolic Profiling of Octadecanoid Oxylipins

et al. 2022

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Octadecanoids are broadly defined as oxylipins (i.e., lipid mediators) derived from 18-carbon fatty acids. In contrast to the well-studied eicosanoids, there is a lack of analytical methods for octadecanoids, hampering further investigations in the field. We developed an integrated workflow combining chiral separation by supercritical fluid chromatography (SFC) and reversed-phase liquid chromatography (LC) coupled to tandem mass spectrometry detection for quantification of a broad panel of octadecanoids. The platform includes 70 custom-synthesized analytical and internal standards to extend the coverage of the octadecanoid synthetic pathways. A total of 103 octadecanoids could be separated by chiral SFC and complex enantioseparations could be performed in <13 min, while the achiral LC method separated 67 octadecanoids in 13.5 min. The LC method provided a robust complementary approach with greater sensitivity relative to the SFC method. Both methods were validated in solvent and surrogate matrix in terms of linearity, lower limits of quantification (LLOQ), recovery, accuracy, precision, and matrix effects. Instrumental linearity was good for both methods (R 2 > 0.995) and LLOQ ranged from 0.03 to 6.00 ng/mL for SFC and 0.01 to 1.25 ng/mL for LC. The average accuracy in the solvent and surrogate matrix ranged from 89 to 109% in SFC and from 106 to 220% in LC, whereas coefficients of variation (CV) were <14% (at medium and high concentrations) and 26% (at low concentrations). Validation in the surrogate matrix showed negligible matrix effects (<16% for all analytes), and average recoveries ranged from 71 to 83%. The combined methods provide a platform to investigate the biological activity of octadecanoids and expand our understanding of these little-studied compounds.

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Section: Resultsmentioning

confidence: 99%

Development of a Chiral Supercritical Fluid Chromatography–Tandem Mass Spectrometry and Reversed-Phase Liquid Chromatography–Tandem Mass Spectrometry Platform for the Quantitative Metabolic Profiling of Octadecanoid Oxylipins

et al. 2022

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“…A total of 67 species were included in the method, of which 62 could be obtained as isolated pure standards. PhytoPs and PhytoFs were only included in the LC method because they possess multiple chiral centers in combination with multiple double bond configurations, the resolution of which would lead to complex chromatography 30 . Additionally, because PhytoPs and PhytoFs are produced by autoxidation, the resulting signal splitting in the racemic mixtures of diastereoisomers would result in sensitivity decrease.…”

Section: Achiral Lc Methods Developmentmentioning

confidence: 99%

Development of a chiral SFC-MS/MS and reversed-phase LC-MS/MS platform for the quantitative metabolic profiling of octadecanoid oxylipins

Quaranta

Zöhrer

Revol-Cavalier

et al. 2022

Preprint

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Octadecanoids are broadly defined as oxylipins (i.e., lipid mediators) derived from 18-carbon fatty acids. In contrast to the well-studied eicosanoids, there is a lack of analytical methods for octadecanoids, hampering further investigations in the field. We developed an integrated workflow combining chiral separation by supercritical fluid chromatography (SFC) and reversed-phase liquid chromatography (LC) coupled to tandem-MS detection for quantification of a broad panel of octadecanoids. The platform included 70 custom-synthesized analytical and internal standards to extend the coverage of the octadecanoid synthetic pathways. A total of 103 octadecanoids could be separated by chiral SFC and complex enantioseparations could be performed in <13 minutes, while the achiral LC method separated 67 species in 13.5 minutes. The LC method provided a robust complementary approach with greater sensitivity relative to the SFC method. Both methods were validated in solvent and surrogate matrix in terms of linearity, lower limits of quantification (LLOQ), recovery, accuracy, precision, and matrix effects. Instrumental linearity was good for both methods (R2>0.995) and LLOQ ranged from 0.03-6.00 ng/mL for SFC and 0.01-1.25 ng/mL for LC. The average accuracy in solvent and surrogate matrix ranged from 89-109% in SFC and from 106-220% in LC, whereas coefficients of variation (CV) were <14% (at medium and high concentration) and 26% (at low concentration). Validation in surrogate matrix showed negligible matrix effects (<16% for all analytes) and average recoveries ranged from 71-83%. The combined methods provide a platform to investigate the biological activity of octadecanoids and expand our understanding of these little studied compounds.

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“…In seven further steps, alkoxyamine 241 was then successfully transferred to 15-F 2t -isoprostane. 1216,1217 In addition, the oxidative radical cyclization was also applied to the synthesis of fusarisetin A, 1218 phytoprostanes, 1219 trioxygenated 16-phytoprostanes, 1220 the methyl ester of a potential metabolite of 15-E 2 -isoprostane, 1221 and nonenzymatic polyunsaturated fatty acids. 1222 Jahn and co-workers also developed an elegant protocol that uses ferrocene in a catalytic amount in combination with the TEMPO oxoammonium salt as the stoichiometric oxidant (Scheme 73).…”

Section: Trapping Of C-centered Radicalsmentioning

confidence: 99%

“…TEMPO trapping delivers alkoxyamine 241 in 41% yield along with its diastereoisomer 241′ . In seven further steps, alkoxyamine 241 was then successfully transferred to 15-F 2t -isoprostane. , In addition, the oxidative radical cyclization was also applied to the synthesis of fusarisetin A, phytoprostanes, trioxygenated 16-phytoprostanes, the methyl ester of a potential metabolite of 15-E 2 -isoprostane, and nonenzymatic polyunsaturated fatty acids …”

Section: Nitroxides In Free-radical Chemistrymentioning

confidence: 99%

Organic Synthesis Using Nitroxides

Leifert

Studer

2023

Chem. Rev.

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Nitroxides, also known as nitroxyl radicals, are long-lived or stable radicals with the general structure R 1 R 2 N−O • . The spin distribution over the nitroxide N and O atoms contributes to the thermodynamic stability of these radicals. The presence of bulky N-substituents R 1 and R 2 prevents nitroxide radical dimerization, ensuring their kinetic stability. Despite their reactivity toward various transient C radicals, some nitroxides can be easily stored under air at room temperature. Furthermore, nitroxides can be oxidized to oxoammonium salts (R 1 R 2 N�O + ) or reduced to anions (R 1 R 2 N−O − ), enabling them to act as valuable oxidants or reductants depending on their oxidation state. Therefore, they exhibit interesting reactivity across all three oxidation states. Due to these fascinating properties, nitroxides find extensive applications in diverse fields such as biochemistry, medicinal chemistry, materials science, and organic synthesis. This review focuses on the versatile applications of nitroxides in organic synthesis. For their use in other important fields, we will refer to several review articles. The introductory part provides a brief overview of the history of nitroxide chemistry. Subsequently, the key methods for preparing nitroxides are discussed, followed by an examination of their structural diversity and physical properties. The main portion of this review is dedicated to oxidation reactions, wherein parent nitroxides or their corresponding oxoammonium salts serve as active species. It will be demonstrated that various functional groups (such as alcohols, amines, enolates, and alkanes among others) can be efficiently oxidized. These oxidations can be carried out using nitroxides as catalysts in combination with various stoichiometric terminal oxidants. By reducing nitroxides to their corresponding anions, they become effective reducing reagents with intriguing applications in organic synthesis. Nitroxides possess the ability to selectively react with transient radicals, making them useful for terminating radical cascade reactions by forming alkoxyamines. Depending on their structure, alkoxyamines exhibit weak C−O bonds, allowing for the thermal generation of C radicals through reversible C−O bond cleavage. Such thermally generated C radicals can participate in various radical transformations, as discussed toward the end of this review. Furthermore, the application of this strategy in natural product synthesis will be presented.

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First Total Synthesis of Phytoprostanes with Prostaglandin‐Like Configuration, Evidence for Their Formation in Edible Vegetable Oils and Orienting Study of Their Biological Activity

Cited by 5 publications

References 76 publications

Development of a Chiral Supercritical Fluid Chromatography–Tandem Mass Spectrometry and Reversed-Phase Liquid Chromatography–Tandem Mass Spectrometry Platform for the Quantitative Metabolic Profiling of Octadecanoid Oxylipins

Development of a Chiral Supercritical Fluid Chromatography–Tandem Mass Spectrometry and Reversed-Phase Liquid Chromatography–Tandem Mass Spectrometry Platform for the Quantitative Metabolic Profiling of Octadecanoid Oxylipins

Development of a chiral SFC-MS/MS and reversed-phase LC-MS/MS platform for the quantitative metabolic profiling of octadecanoid oxylipins

Organic Synthesis Using Nitroxides

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