Fatty Acids and their Derivatives

and, Anders Vik; Hansen, Trond Vidar

doi:10.1002/9781118754085.ch3

Cited by 5 publications

(3 citation statements)

References 85 publications

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“…The SPMs and their metabolites are biosynthesized in the nano- to picogram scale, hence the structural authentication of the biogenic products by direct NMR analyses is not possible. To determine whether oxidation at the carbon 20 position represents the foremost route of RvE4 ( 1 ) further metabolism in human phagocytes, we incubated RvE4 ( 1 ) with isolated human PMNs (Figure ).…”

Section: Results and Discussionmentioning

confidence: 99%

“…The pyridine helps reduce the activity of the diverse catalyst, wherein the 1-octene diminishes the tendency of overreduction. To cleave the three silyl ethers in 14, catalytic amounts of acetic chloride in MeOH, using dry conditions, afforded the 20-OH-RvE4 methyl ester (15) The SPMs and their metabolites are biosynthesized in the nano-to picogram scale, 29 hence the structural authentication of the biogenic products by direct NMR analyses is not possible. To determine whether oxidation at the carbon 20 position represents the foremost route of RvE4 (1) further metabolism in human phagocytes, we incubated RvE4 (1) with isolated human PMNs (Figure 3).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

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Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4)

Reinertsen,

Libreros,

Nshimiyimana

et al. 2023

ACS Pharmacol. Transl. Sci.

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Resolvin E4 (RvE4) belongs to the resolvin family of specialized pro-resolving mediators (SPMs). The resolvins are endogenously formed mediators with both potent pro-resolving and anti-inflammatory biological activities and have attracted considerable attention in both inflammation research and drug discovery. Hence, further metabolism of the resolvins is of interest. Gaining knowledge about the structure–function of further metabolites of the resolvins is important due to their interest in drug-discovery efforts. For the first time, the total synthesis and biological evaluations of the ω-20 hydroxylated metabolite of RvE4, named herein 20-OH-RvE4, are presented. RvE4 was converted to 20-OH-RvE4 by human polymorphonuclear leukocytes. LC–MS/MS analysis and UV spectrophotometry reveal that the synthetic 20-OH-RvE4 matched RvE4-converted product 20-OH-RvE4 by human neutrophils. Cellular studies have revealed that RvE4 is formed from eicosapentaenoic acid in physiologic hypoxia by human neutrophils and macrophages, and we herein established that 20-OH-RvE4 is a secondary metabolite formed by the ω-oxidation of RvE4 in human neutrophils. A direct comparison of the biological actions between RvE4 and its metabolic product suggested that 20-OH-RvE4 displayed reduced bioactions in stimulating the efferocytosis of human senescent erythrocytes by human M2-like macrophages. At concentrations down to 0.1 nM, RvE4 increased macrophage erythrophagocytosis, an important pro-resolving function that was diminished due to metabolic transformation. The results provided herein contribute to a novel molecular insight on the further local metabolization of RvE4, the newest member among the SPM superfamily.

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Section: Results and Discussionmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4)

Reinertsen,

Libreros,

Nshimiyimana

et al. 2023

ACS Pharmacol. Transl. Sci.

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“…Biologically active oxygenated natural products derived from the two ω-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid and arachidonic acid, have for a long time been the topic of biological and biosynthetic investigations [ 1 , 2 ], but also targets for stereoselective total synthesis [ 3 ]. Examples of classes of such natural products are prostaglandins [ 4 ], leukotrienes [ 5 ], lipoxins [ 6 ], resolvins, maresins, protectins [ 7 ], epoxy fatty acids [ 8 ] and oxylipins [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid

et al. 2022

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Monohydroxylated polyunsaturated fatty acids belonging to the oxylipin class of natural products are present in marine and terrestrial sources as well as in the human body. Due to their biological activities and role in diverse biosynthetic pathways, oxylipins biosynthesized from eicosapentaenoic acid and arachidonic acid have attracted great interest from the scientific community. One example is 3-hydroxyeicosapentaenoic acid where the absolute configuration at C-3 has only been tentatively assigned. In this paper, studies on acetate type aldol reactions that enabled the preparation of 3-(R)-hydroxyeicosapentaenoic acid (3R-HETE, 2) and its enantiomer are presented.

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Stereoselective Synthesis, Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2_{n‐3 DPA}

Reinertsen

Primdahl

Matteis

et al. 2021

Chemistry A European J

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Herein we report the first total synthesis of RvD2n‐3 DPA, an endogenously formed mediator biosynthesized from the omega‐3 fatty acid n‐3 docosapentaenoic acid. The key steps are the Midland Alpine borane reduction, Sonogashira cross‐coupling reactions, and a Z‐selective alkyne reduction protocol, yielding RvD2n‐3 DPA methyl ester in 13 % yield over 12 steps (longest linear sequence). The physical property data (UV chromophore, chromatography and MS/MS fragmentation) of the synthetic lipid mediator matched those obtained from biologically produced material. Moreover, synthetic RvD2n‐3 DPA also carried the potent biological activities of enhancing macrophage uptake of Staphylococcus aureus and zymosan A bioparticles.

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Fatty Acids and their Derivatives

Cited by 5 publications

References 85 publications

Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4)

Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4)

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid

Stereoselective Synthesis, Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2_{n‐3 DPA}

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Fatty Acids and their Derivatives

Cited by 5 publications

References 85 publications

Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4)

Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4)

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid

Stereoselective Synthesis, Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2n‐3 DPA

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Stereoselective Synthesis, Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2_{n‐3 DPA}