Amalie Føreid Reinertsen

• Reinertsen, Amalie Føreid; Vik, Anders & Hansen, Trond Vidar (2024). Biology and Total Synthesis of n-3 Docosapentaenoic Acid-Derived Specialized Pro-Resolving Mediators. Molecules. ISSN 1431-5157. 29(12). doi: 10.3390/molecules29122833. Full text in Research Archive
• Ervik, Karina; Reinertsen, Amalie Føreid; Koenis, Duco S.; Dalli, Jesmond & Hansen, Trond Vidar (2023). Stereoselective Synthesis, Pro-resolution, and Anti-inflammatory Actions of RvD5n-3 DPA. Journal of natural products. ISSN 0163-3864. 86(11), p. 2546–2553. doi: 10.1021/acs.jnatprod.3c00769. Full text in Research Archive Show summary

  The methyl ester of resolvin D5n-3 DPA, a lipid mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid, was stereoselectively prepared in 8% yield over 12 steps (longest linear sequence). The key steps for the introduction of the two stereogenic secondary alcohols were an organocatalyzed oxyamination and the Midland Alpine borane reduction. For the assembly of the carbon chain, the Sonogashira cross-coupling reaction and the Takai olefination were utilized. The physical properties, including retention time in liquid chromatography and tandem mass spectra, of the synthetic material were matched against material from human peripheral blood and mouse infectious exudates. Synthetic RvD5n-3 DPA, obtained just prior to biological experiments, displayed potent leukocyte-directed activities, upregulating the ability of neutrophils and macrophages to phagocytose bacteria, known as hallmark bioactions of specialized pro-resolving endogenous mediators.

• Reinertsen, Amalie Føreid; Libreros, Stephania; Nshimiyimana, Robert; Serhan, Charles Nicholas & Hansen, Trond Vidar (2023). Metabolization of Resolvin E4 by ω-Oxidation in Human Neutrophils: Synthesis and Biological Evaluation of 20-Hydroxy-Resolvin E4 (20-OH-RvE4). ACS Pharmacology & Translational Science. 6(12), p. 1898–1908. doi: 10.1021/acsptsci.3c00201. Full text in Research Archive Show summary

  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.

• Reinertsen, Amalie Føreid; Primdahl, Karoline Gangestad; Shay, Ashley E.; Serhan, Charles Nicholas; Hansen, Trond Vidar & Aursnes, Marius (2021). Stereoselective Synthesis and Structural Confirmation of the Specialized Pro-Resolving Mediator Resolvin E4. Journal of Organic Chemistry. ISSN 0022-3263. 86(4), p. 3535–3545. doi: 10.1021/acs.joc.0c02913. Full text in Research Archive Show summary

  Herein, we report the stereoselective and convergent synthesis of resolvin E4, a newly identified specialized pro-resolving mediator. This synthesis proves the absolute configuration and exact olefin geometry. Key elements of the successful strategy include a highly stereoselective MacMillan organocatalytic oxyamination, a Midland Alpine borane reduction, and the use of a 1,4-pentadiyne unit as a linchpin building block. The application of reaction telescoping in several of the synthetic transformations enabled the preparation of the resolvin E4 methyl ester in 10% yield over 10 steps (longest linear sequence). The physical property (UV–Vis and LC–MS/MS) data of synthetic resolvin E4 matched those obtained from biologically produced material.

• Reinertsen, Amalie Føreid; Primdahl, Karoline Gangestad; Matteis, Roberta De; Dalli, Jesmond & Hansen, Trond Vidar (2021). Stereoselective Synthesis, Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2n-3 DPA. Chemistry - A European Journal. ISSN 0947-6539. 27. doi: 10.1002/chem.202103857. Full text in Research Archive Show summary

  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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• The, Daniel; Reinertsen, Amalie Føreid; Vik, Anders & Hansen, Trond Vidar (2025). Synthetic Studies Towards RvD1 Analogs. Full text in Research Archive
• Høyby, Isak; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2025). Synthetic studies toward 17R-docosahexaenoic acid. Full text in Research Archive
• Reinertsen, Amalie Føreid (2024). Stereoselective Synthesis, Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2n-3 DPA. Full text in Research Archive
• Amundrød, Kristian; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2024). Synthetic Studies Towards RvD1n-3 DPA Analogs. Full text in Research Archive
• Reinertsen, Amalie Føreid (2024). Syntese og biologiske evalueringer av nye omega-3-fettsyrederivater. Norsk Farmasøytisk Tidsskrift (NFT). Full text in Research Archive
• Büsser, Jonathan; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2024). Synthetic Studies Towards an Analogue of the SPM RvD1n-3 DPA. Full text in Research Archive
• Reinertsen, Amalie Føreid; Hansen, Trond Vidar; Nuruddin, Syed Mohammad & Serhan, Charles N (2024). Stereoselective Synthesis and Biological Evaluations of Pro-resolution and Radiotracer Agents. Full text in Research Archive
• Ervik, Karina; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2023). Total synthesis of the specialized pro-resolving mediator RvD5n-3 DPA. Full text in Research Archive
• Ervik, Karina; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2023). Synthetic studies towards the specialized pro-resolving mediator RvD5n-3 DPA. Full text in Research Archive
• Bjørndal, Emma; Cong, Victoria; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2023). Synthetic Studies Towards the Specialized Pro-resolving Mediator RvD1n-3 DPA Analogs. Full text in Research Archive
• Ervik, Karina; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2022). Synthetic studies towards the specialized pro-resolving mediator RvD5n-3 DPA. Full text in Research Archive
• Lerstad, Nora Dotterud; Reinertsen, Amalie Føreid; Tungen, Jørn Eivind & Hansen, Trond Vidar (2020). Synthetic Studies Towards an Analog of RvD1n-3 DPA. Full text in Research Archive
• Reinertsen, Amalie Føreid (2024). Stereoselective Syntheses and Biological Evaluations of Novel Resolvins. Universitetet i Oslo. Full text in Research Archive Show summary

  Research has revealed that omega-3 polyunsaturated fatty acids, like docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and n-3 docosapentaenoic acid (DPA), are converted to hydroxylated products in the human body. These products have shown promising results regarding their anti-inflammatory and pro-resolving actions. In-depth knowledge about their biosynthesis and establishment of their exact chemical structure is crucial to better understand their biological properties. This thesis has contributed with new knowledge about the chemical structure of some novel hydroxylated omega-3 products by utilizing synthetic organic chemistry. These synthetic efforts have enabled cell culture studies and biological experiments in mice to give evidence about their biosynthesis and biological actions. Furthermore, the project has contributed to new information about how these hydroxylated omega-3 fatty acid derivatives prevents the development of uncontrolled inflammation, in addition to demonstrating their anti-bacterial and anti-fungal actions. Altogether, this is of great interest to enable the discovery and development of new anti-inflammatory and anti-microbial therapeutics in the future. The experimental work has been conducted at the Department of Pharmacy, University of Oslo, and the biological work has been performed by our colleagues in the Serhan group at Harvard Medical School and in the Dalli group at Queen Mary University of London.

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