Trond Vidar Hansen

• Bathen, Mina; Sigurjónsson, Svanur; Malterud, Karl Egil; Hasselstrøm, Daniel Haga; Gani, Osman & Vik, Anders [Vis alle 9 forfattere av denne artikkelen] (2026). A modular semi-synthetic approach to form a DHA-like polyunsaturated ether lipid with 15-lipoxygenase-1 substrate activity. Organic and biomolecular chemistry. ISSN 1477-0520. doi: 10.1039/d6ob00245e. Fulltekst i vitenarkiv Vis sammendrag

  In this work a docosahexaenoic acid-like-methoxylated ether lipid was synthesised using a novel semi-synthetic approach, from natural docosahexaenoic acid and commercially available (2′ S )-epichlorohydrin and (2 R )-solketal.

• 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. Fulltekst i vitenarkiv
• Nolsøe, Jens Mortansson Jelstrup; Underhaug, Jarl; Sørskår, Åshild Moi; Antonsen, Simen; Malterud, Karl Egil & Gani, Osman [Vis alle 11 forfattere av denne artikkelen] (2024). Biological Evaluations, NMR Analyses, Molecular Modeling Studies, and Overview of the Synthesis of the Marine Natural Product (−)-Mucosin. Molecules. ISSN 1431-5157. 29(5). doi: 10.3390/molecules29050994. Fulltekst i vitenarkiv Vis sammendrag

  Natural products obtained from marine organisms continue to be a rich source of novel structural architecture and of importance in drug discovery, medicine, and health. However, the success of such endeavors depends on the exact structural elucidation and access to sufficient material, often by stereoselective total synthesis, of the isolated natural product of interest. (−)-Mucosin (1), a fatty acid derivative, previously presumed to contain a rare cis-bicyclo[4.3.0]non-3-ene moiety, has since been shown to be the trans-congener. Analytically, the fused bicyclic ring system in (−)-1 constitutes a particular challenge in order to establish its relative and absolute stereochemistry. Herein, data from biological evaluations, NMR and molecular modeling studies of (−)-1 are presented. An overview of the synthetic strategies enabling the exact structural elucidation of (−)-mucosin (1) is also presented.

• Ervik, Karina; Li, Yi-Ze; Ji, Ru-Rong; Serhan, Charles N. & Hansen, Trond Vidar (2024). Synthesis of the methyl ester of 17(R/S)-Me-RvD5n-3 DPA and relief of postoperative pain in male mice. Organic and biomolecular chemistry. ISSN 1477-0520. 22(47), s. 9266–9270. doi: 10.1039/d4ob01534g. Fulltekst i vitenarkiv
• 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), s. 2546–2553. doi: 10.1021/acs.jnatprod.3c00769. Fulltekst i vitenarkiv Vis sammendrag

  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), s. 1898–1908. doi: 10.1021/acsptsci.3c00201. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Haatveit, Åsmund Steinvik & Hansen, Trond Vidar (2023). The biosynthetic pathways of the protectins. Prostaglandins & Other Lipid Mediators. ISSN 1098-8823. 169. doi: 10.1016/j.prostaglandins.2023.106787. Fulltekst i vitenarkiv Vis sammendrag

  Evidence for the biosynthetic pathways of the specialized pro-resolving mediator (SPM) protectin D1 (PD1) and its biochemical further local metabolism were presented during the 8th European Workshop on Lipid Mediators, organized June 29th-July 1st, 2022, in Stockholm, Sweden. Herein, we provide an extended and detailed discussion of these topics. PD1, one of 43 SPMs reported so far, exhibits very potent pro-resolution and anti-inflammatory bioactions. Many research groups worldwide have confirmed these and other interesting bioactions. The protectins constitute, together with the lipoxins, resolvins, and maresins, the four individual SPM families, which have received a great interest in basic biomedical research and drug discovery efforts.

• Furutani, Kenta; Chen, Ouyang; McGinnis, Aidan K.; Wang, Yuqing; Serhan, Charles N & Hansen, Trond Vidar [Vis alle 7 forfattere av denne artikkelen] (2022). Novel proresolving lipid mediator mimetic 3-oxa-PD1n-3 docosapentaenoic acid reduces acute and chronic itch by modulating excitatory and inhibitory synaptic transmission and astroglial secretion of lipocalin-2 in mice. Pain. ISSN 0304-3959. 164(6), s. 1340–1354. doi: 10.1097/j.pain.0000000000002824. Fulltekst i vitenarkiv Vis sammendrag

  Specialized pro-resolving mediators (SPMs) have demonstrated potent analgesic actions in animal models of pathological pain. The actions of SPMs in acute and chronic itch are currently unknown. Recently, n-3 docosapentaenoic acid (DPA) was found to be a substrate for the biosynthesis of several novel families of SPMs and 3-oxa-PD1n-3 DPA (3-oxa-PD1) is an oxidation-resistant metabolic stable analogue of the n-3 DPA-derived protectin D1 (PD1). Herein, we demonstrate that 3-oxa-PD1 effectively reduces both acute and chronic itch in mouse models. Intrathecal injection of 3-oxa-PD1 (100 ng) reduced acute itch induced by either histamine, chloroquine, or morphine. Furthermore, intrathecal 3-oxa-PD1 effectively reduced chronic itch, induced by cutaneous T cell lymphoma (CTCL), allergic contact dermatitis with dinitrofluorobenzene, and psoriasis by imiquimod. Intratumor injection of Oxa-PD1 also suppressed CTCL-induced chronic itch. Strikingly, the anti-pruritic effect lasted for several weeks after 1-week intrathecal 3-oxa-PD1 treatment. Whole-cell recordings revealed significant increase in excitatory postsynaptic currents in spinal dorsal horn (SDH) neurons of CTCL mice, but this increase was blocked by 3-oxa-PD1. 3-oxa-PD1 further increased inhibitory postsynaptic currents in SDH neurons of CTCL mice. CTCL increased the spinal levels of lipocalin-2 (LCN2), an itch mediator produced by astrocytes. 3-oxa-PD1 suppressed LCN2 production in CTCL mice and LCN2 secretion in astrocytes. Finally, CTCL-induced anxiety was alleviated by intrathecal 3-oxa-PD1. Our findings suggest that 3-oxa-PD1 potently inhibits acute and chronic itch via regulation of excitatory/inhibitory synaptic transmission and astroglial LCN2 production. Therefore, stable SPM analogs such as 3-oxa-PD1 could be useful to treat pruritus associated with different skin injuries.

• Ammazzalorso, Alessandra & Hansen, Trond Vidar (2022). Combretastatin Derivatives as Tubulin Inhibitors: A Fascinating Journey from Nature to Drug Discovery Strategies. I Carradori, Simone (Red.), Flavonoids and Phenolics. Bentham Science Publishers. ISSN 9789815079104. s. 112–144. doi: 10.2174/9789815079098122010007. Fulltekst i vitenarkiv
• Hansen, Trond Vidar & Serhan, Charles N. (2022). Protectins: Their biosynthesis, metabolism and structure-functions. Biochemical Pharmacology. ISSN 0006-2952. 206. doi: 10.1016/j.bcp.2022.115330. Fulltekst i vitenarkiv Vis sammendrag

  Several lipoxygenase enzymes and cyclooxygenase-2 stereoselectively convert the polyunsaturated fatty acids arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and n-3 docosapentaenoic acid into numerous oxygenated products. Biosynthetic pathway studies have shown, during the resolution phase of acute inflammation, that distinct families of endogenous products are formed. These products were named specialized pro-resolving mediators, given their specialized functions in the inflammation-resolution circuit, enhancing the return of inflamed and injured tissue to homeostasis. The lipoxins, resolvins, protectins and maresins, together with the sulfido-conjugates of the resolvins, protectins and maresins, constitute the four individual families of these local mediators. When administrated in vivo in a wide range of human disease models, the specialized pro-resolving mediators display potent bioactions. The detailed and individual biosynthetic steps constituting the biochemical pathways, the metabolism, recent reports on structure–function studies and pharmacodynamic data of the protectins, are presented herein. Emphasis is on the structure–function results on the recent members of the sulfido conjugated protectins and further metabolism of protectin D1. Moreover, the members of the individual families of specialized pro-resolving mediators and their biosynthetic precursor are presented. Today 43 specialized pro-resolving mediators possessing pro-resolution and anti-inflammatory bioactions are reported and confirmed, constituting a basis for resolution pharmacology. This emerging biomedical field provides a new approach for drug discovery, that is also discussed.

• Ervik, Karina & Hansen, Trond Vidar (2022). Enantioselective Trost alkynylation with 2E,4E-5-bromo-2,4-pentadienal. Tetrahedron Letters. ISSN 0040-4039. 100. doi: 10.1016/j.tetlet.2022.153879. Fulltekst i vitenarkiv Vis sammendrag

  The synthetically useful aldehyde 2E,4E-5-bromo-2,4-pentadienal was subjected to the enantioselective Trost alkynylation protocol, yielding highly functionalized propargylic secondary alcohols in an enantioselective manner. In most cases, the isolated yields and enantiomeric excess of the products were modest to high, but several products were formed in both high yields and enantiomeric excess.

• Balta, Maria; Schreurs, Olaf Joseph Franciscus; Hansen, Trond Vidar; Tungen, Jørn Eivind; Vik, Anders & Glaab, Enrico [Vis alle 10 forfattere av denne artikkelen] (2022). Expression and function of resolvin RvD1n-3 DPA receptors in oral epithelial cells. European Journal of Oral Sciences. ISSN 0909-8836. 130:e12883(4), s. 1–10. doi: 10.1111/eos.12883. Fulltekst i vitenarkiv Vis sammendrag

  Chronic inflammatory responses can inflict permanent damage to host tissues. Specialized pro-resolving mediators downregulate inflammation but also can have other functions. The aim of this study was to examine whether oral epithelial cells express the receptors FPR2/ALX and DRV1/GPR32, which bind RvD1n-3 DPA, a recently described pro-resolving mediator derived from omega-3 docosapentaenoic acid (DPA), and whether RvD1n-3 DPA exposure induced significant responses in these cells. Gingival biopsies were stained using antibodies to FPR2/ALX and DRV1/GPR32. Expression of FPR2/ALX and DRV1/GPR32 was examined in primary oral epithelial cells by qRT-PCR, flow cytometry, and immunofluorescence. The effect of RvD1n-3 DPA on intracellular calcium mobilization and transcription of beta-defensins 1 and 2, and cathelicidin was evaluated by qRT-PCR. FPR2/ALX and DRV1/GPR32 were expressed by gingival keratinocytes in situ. In cultured oral epithelial cells, FPR2/ALX was detected on the cell surface, whereas FPR2/ALX and DRV1/GPR32 were detected intracellularly. Exposure to RvD1n-3 DPA induced intracellular calcium mobilization, FPR2/ALX internalization, DRV1/GPR32 translocation to the nucleus, and significantly increased expression of genes coding for beta-defensin 1, beta-defensin 2, and cathelicidin. This shows that the signal constituted by RvD1n-3 DPA is recognized by oral keratinocytes and that this can strengthen the antimicrobial and regulatory potential of the oral epithelium.

• Gjessing, Gard; Johnsen, Lars-Inge Gammelsæter; Antonsen, Simen; Nolsøe, Jens Mortansson Jelstrup; Stenstrøm, Yngve H. & Hansen, Trond Vidar (2022). The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid. Molecules. ISSN 1431-5157. 27(7). doi: 10.3390/molecules27072295. Fulltekst i vitenarkiv Vis sammendrag

  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.

• 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), s. 3535–3545. doi: 10.1021/acs.joc.0c02913. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Nesman, Jannicke Irina; Chen, Ouyang; Luo, Xin; Ji, Ru-Rong; Serhan, Charles N. & Hansen, Trond Vidar (2021). A new synthetic protectin D1 analog 3-oxa-PD1n-3 DPA reduces neuropathic pain and chronic itch in mice. Organic and biomolecular chemistry. ISSN 1477-0520. 19, s. 2744–2752. doi: 10.1039/d0ob02136a. Fulltekst i vitenarkiv Vis sammendrag

  The resolution of inflammation is a biosynthetically active process controlled by the interplay between oxygenated polyunsaturated mediators and G-protein coupled receptor-signaling pathways. These enzymatically oxygenated polyunsaturated fatty acids belong to distinct families of specialized pro-resolving autacoids. The protectin family of mediators has attracted an interest because of their potent pro-resolving and anti-inflammatory actions verified in several in vivo disease models. Herein, we present the stereoselective synthesis and biological evaluations of 3-oxa-PD1n-3 DPA, a protectin D1 analog. Results from mouse models indicate that the mediators protectin D1, PD1n-3 DPA and the new analog 3-oxa-PD1n-3 DPA all relieved streptozotocin-induced diabetic neuropathic pain at doses of 90 and 300 pmol, equivalent to 30 and 100 ng, respectively, following intrathecal (I.T.) injection. Of interest, at a low dose of only 30 pmol (10 ng; I.T.) only 3-oxa PD1n-3 DPA was able to alleviate neuropathic pain, directly compared to vehicle controls. Moreover, using a chronic itch model of cutaneous T-cell lymphoma (CTCL), all three compounds at 300 pmol (100 ng) showed a significant reduction in itching for several hours. The biomolecular information on the structure-functions of the protectins and the new synthetic analog 3-oxa-PD1n-3 DPA is of interest towards developing new immunoresolvents.

• Vik, Anders & Hansen, Trond Vidar (2021). Stereoselective syntheses and biological activities of E-series resolvins. Organic and biomolecular chemistry. ISSN 1477-0520. 19(4), s. 705–721. doi: 10.1039/d0ob02218g. Fulltekst i vitenarkiv Vis sammendrag

  Recent research efforts focusing on the many mechanisms participating in the resolution of acute inflammation have uncovered a new genus of pro-resolving lipid mediators. These endogenous molecules include the lipoxins, resolvins, protectins and maresins, collectively coined specialized pro-resolving mediators (SPMs). SPMs are oxygenated polyunsaturated fatty acids biosynthesized by lipoxygenases and cyclooxygenases enzymes. These chemically sensitive molecules are produced in nano- to pico-gram amounts in vivo and exhibit potent anti-inflammatory and pro-resolving bioactions. In addition, SPMs clear bacterial infections, reduce pain and display bioactivities towards host defense, organ protection and tissue remodeling. Altogether, these bioactions and the need for synthetic SPMs for determination of absolute configuration and in vivo experiments have spurred a great interest in the synthetic and biomolecular communities. This review covers reported stereoselective total syntheses and outlines the most significant bioactions of the E-series resolvins.

• 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. Fulltekst i vitenarkiv Vis sammendrag

  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.

• Pangopoulos, Maria Kant; Nolsøe, Jens Mortansson Jelstrup; Antonsen, Simen Gjelseth; Colas, Romain; Dalli, Jesmond & Aursnes, Marius [Vis alle 8 forfattere av denne artikkelen] (2020). Enzymatic studies with 3-oxa n-3 DPA. Bioorganic chemistry (Print). ISSN 0045-2068. 96. doi: 10.1016/j.bioorg.2020.103653. Fulltekst i vitenarkiv Vis sammendrag

  Cyclooxygenase-2 and several lipoxygenases convert polyunsaturated fatty acids into a large variety of products. During inflammatory processes, these enzymes form several distinct families of specialized pro-resolving lipid mediators possessing potent anti-inflammatory and pro-resolving effects. These mediators have attracted a great interest as leads in drug discovery and have recently been the subject of biosynthetic pathway studies using docosahexaenoic and n-3 docosapentaenoic acid as substrates. Herein we present enzymatic studies with cyclooxygenase-2 and 5-, 12- and 15-lipoxygenase enzymes using 3-oxa n-3 DPA as a synthetic mimic of n-3 docosapentaenoic acid. Structural elucidation based on data from RP-HPLC UV and LC/MS-MS experiments enabled the identification of novel enzymatically formed products. These findings constitute the basis for further biosynthetic studies towards understanding the mechanisms regulating substrate utilization in the biosynthesis of specialized pro-resolving lipid mediators.

• Nesman, Jannicke Irina; Tungen, Jørn Eivind; Vik, Anders & Hansen, Trond Vidar (2020). Stereoselective Synthesis of the Specialized Pro-resolving and Anti-inflammatory Mediator Resolvin E1. Tetrahedron. ISSN 0040-4020. 76(3), s. 130821–130821. doi: 10.1016/j.tet.2019.130821. Fulltekst i vitenarkiv
• Solum, Eirik Johansson; Liekens, Sandra & Hansen, Trond Vidar (2020). Synthesis and Biological Evaluation of Analogs of Didehydroepiandrosterone as Potential New Anticancer Agents. Molecules. ISSN 1431-5157. 25(13), s. 1–9. doi: 10.3390/molecules25133052. Fulltekst i vitenarkiv Vis sammendrag

  The synthesis, cytotoxicity and inhibition of CDK8 by thirteen analogs of cortistatin A are reported. These efforts revealed that the analogs with either a 6- or 7-isoquinoline or 5-indole side chain in the 17-position are the most promising anti-proliferative agents. These compounds showed potent cytotoxic effects in CEM, HeLa and HMEC-1 cells. All three compounds exhibited IC50 values < 10µM. The most interesting 10l analog exhibited an IC50 value of 0.59 µM towards the human dermal microvascular endothelial cell line (HMEC-1), significantly lower than the reference standard 2-methoxyestradiol. At a concentration at 50 nM the most potent 10h compound reduced the activity of CDK8 to 35%.

• Paluchova, Veronika; Vik, Anders; Cajka, Tomas; Brezinova, Maria; Brejchova, Krisyna & Bugajev, Viktor [Vis alle 15 forfattere av denne artikkelen] (2020). Triacylglycerol‐Rich Oils of Marine Origin are Optimal Nutrients for Induction of Polyunsaturated Docosahexaenoic Acid Ester of Hydroxy Linoleic Acid (13‐DHAHLA) with Anti‐Inflammatory Properties in Mice. Molecular Nutrition & Food Research. ISSN 1613-4125. 64(11), s. 1901238–1901238. doi: 10.1002/mnfr.201901238. Fulltekst i vitenarkiv
• Solum, Eirik Johansson; Hansen, Trond Vidar; Aesoy, Reidun & Herfindal, Lars (2020). New CDK8 inhibitors as potential anti-leukemic agents – Design, synthesis and biological evaluation. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 28(10), s. 1–8. doi: 10.1016/j.bmc.2020.115461. Fulltekst i vitenarkiv Vis sammendrag

  Cyclin-dependent kinase 8 (CDK8) plays a vital role in regulating cell transcription either through its association with the mediator complex or by the phosphorylation of transcription factors. CDK8-mediated activation of oncogenes has proved to be important in a variety of cancer types including hematological malignancies. We have designed and synthesized a series of new synthetic steroids. The compounds were evaluated as CDK8 inhibitors in vitro. The three most potent compounds exhibit Kd-values towards CDK8 in the low nanomolar range (3.5–18 nM). Furthermore, the compounds displayed selectivity for CDK8 in a panel of 465 different kinases. The cell studies indicated a selectivity to kill AML-cancer cell lines compared to normal cell lines.

• Tungen, Jørn Eivind; Primdahl, Karoline Gangestad & Hansen, Trond Vidar (2020). The First Total Synthesis of the Lipid Mediator PD2n-3 DPA. Journal of natural products. ISSN 0163-3864. 83(7), s. 2255–2260. doi: 10.1021/acs.jnatprod.0c00385. Fulltekst i vitenarkiv
• Kaupang, Åsmund & Hansen, Trond Vidar (2020). The PPAR Ω Pocket: Renewed Opportunities for Drug Development. PPAR Research. ISSN 1687-4757. 2020. doi: 10.1155/2020/9657380. Fulltekst i vitenarkiv Vis sammendrag

  The past decade of PPARγ research has dramatically improved our understanding of the structural and mechanistic bases for the diverging physiological effects of different classes of PPARγ ligands. The discoveries that lie at the heart of these developments have enabled the design of a new class of PPARγ ligands, capable of isolating central therapeutic effects of PPARγ modulation, while displaying markedly lower toxicities than previous generations of PPARγ ligands. This review examines the emerging framework around the design of these ligands and seeks to unite its principles with the development of new classes of ligands for PPARα and PPARβ/δ. The focus is on the relationships between the binding modes of ligands, their influence on PPAR posttranslational modifications, and gene expression patterns. Specifically, we encourage the design and study of ligands that primarily bind to the Ω pockets of PPARα and PPARβ/δ. In support of this development, we highlight already reported ligands that if studied in the context of this new framework may further our understanding of the gene programs regulated by PPARα and PPARβ/δ. Moreover, recently developed pharmacological tools that can be utilized in the search for ligands with new binding modes are also presented.

• Kristianslund, Renate & Hansen, Trond Vidar (2020). Enantioselective bromolactonization of aryl functionalized alkenoic acids. Tetrahedron Letters. ISSN 0040-4039. 61(15). doi: 10.1016/j.tetlet.2020.151756. Fulltekst i vitenarkiv
• Johansson, Silje; Johannessen, Tonje; Ellefsen, Christiane Færestrand; Ristun, Mali Schulstad; Antonsen, Simen Gjelseth & Hansen, Trond Vidar [Vis alle 8 forfattere av denne artikkelen] (2019). A Convenient Protocol for the Synthesis of Fatty Acid Amides. Synlett : Accounts and Rapid Communications in Synthetic Organic Chemistry. ISSN 0936-5214. 30(2), s. 213–217. doi: 10.1055/s-0037-1611939. Fulltekst i vitenarkiv Vis sammendrag

  Several classes of biologically occurring fatty acid amides have been reported from mammalian and plant sources. Many amides conjugated with fatty acids of mammalian origin exhibit specific activation of individual receptors. Their potential as pharmacological tools or as lead compounds towards the development of novel therapeutics is of great interest. Hence, access to such amides by a practical, high-yielding and scalable protocol without affecting the geometry or position of sensitive functionalities is needed. A protocol that meets all these requirements involves activation of the corresponding acid with carbonyl diimidazole (CDI) followed by reaction with the desired amine or its hydrochloride. More than fifty compounds have been prepared in generally high yields.

• Hansen, Trond Vidar; Vik, Anders & Serhan, Charles N. (2019). The Protectin Family of Specialized Pro-Resolving Mediators: Potent Immunoresolvents Enabling Innovative Approaches to Target Obesity and Diabetes. Frontiers in Pharmacology. 9. doi: 10.3389/fphar.2018.01582. Fulltekst i vitenarkiv Vis sammendrag

  A western type diet and lifestyle play an important role in the development of chronic diseases, yet little insight into the precise cellular and biomolecular mechanisms has emerged. It is known that an unbalanced diet may result in obesity and diabetes. Sufficient amounts and proper balance of omega-6 and omega-3 polyunsaturated fatty acids is key for maintenance of health. The resolution of inflammation is now held to be a biosynthetically actively driven process precisely regulated and controlled by a superfamily of specialized pro-resolving mediators. Specialized pro-resolving mediators are biosynthesized from both omega-6 and omega-3 polyunsaturated fatty acids and are resolution agonists acting on distinct G-coupled protein receptors. These mediators display potent anti-inflammatory and pro-resolving bioactions with EC50-values in the low nanomolar to picomolar range. The protectin family of specialized pro-resolving mediators is biosynthesized from the two omega-3 polyunsaturated fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. All of the protectins display interesting bioactions as anti-inflammatory and pro-resolving agents. This review covers the bioactions, G-coupled protein receptors pharmacology, biosynthesis and medicinal chemistry of the protectin family of specialized pro-resolving mediators with an emphasis on obesity and anti-diabetic effects. In order to enable drug development and medicinal chemistry efforts against these diseases, stereoselective total organic synthesis of each of these mediators is required for confirmation of structure, stereochemical biosynthesis and their functions. We provide an overview of our ongoing efforts and the current knowledge.

• Tungen, Jørn Eivind; Gerstmann, Lisa; Vik, Anders; Mateis, Roberta de; Colas, Romain A. & Dalli, Jesmond [Vis alle 10 forfattere av denne artikkelen] (2019). Resolving Inflammation: Synthesis, Configurational Assignment, and Biological Evaluations of RvD1n−3  DPA. Chemistry - A European Journal. ISSN 0947-6539. 25(6), s. 1476–1480. doi: 10.1002/chem.201806029. Fulltekst i vitenarkiv Vis sammendrag

  New drugs that can resolve inflammation without immunosuppressive effects are at the medicinal chemistry frontier. Pro‐resolving endogenously formed small molecules, that is, the resolvins, are excellent candidates displaying such bioactions. The first total synthesis of the specialized pro‐resolving mediator RvD1n−3 DPA has been achieved using the underutilized sp3–sp3 Negishi cross coupling reaction and an alkyne hydrosilylation–protodesilylation protocol. Biological evaluations revealed that this novel mediator displays low nanomolar pro‐resolving properties and potently activates the human DRV1/GPR32 receptor. As such, this endogenous natural product is a lead compound for the development of novel immunoresolvents.

• Kristianslund, Renate; Tungen, Jørn Eivind & Hansen, Trond Vidar (2019). Catalytic enantioselective iodolactonization reactions. Organic and biomolecular chemistry. ISSN 1477-0520. 17(12), s. 3079–3092. doi: 10.1039/c8ob03160f. Fulltekst i vitenarkiv Vis sammendrag

  The halolactonization reaction is a useful chemical transformation for the construction of lactones from γ- or δ-substituted alkenoic carboxylic acids or carboxylic esters. Traditionally, the stereoselectivity of these reactions has been controlled by the substrates or the reagents. The substrate-controlled method has been extensively studied and applied in the synthesis of many natural products. However, catalytic, enantioselective iodolactonizations of γ- or δ-substituted alkenoic carboxylic acids have only recently been developed. This review article highlights the advances that have emerged over the last decade.

• Arnesen, Liv Henriette; Yasein, Nadia Haj; Tungen, Jørn Eivind; Södling, Helen; Matthews, Jason & Paulsen, Steinar M [Vis alle 10 forfattere av denne artikkelen] (2019). Molecular modelling, synthesis, and biological evaluations of a 3,5-disubstituted isoxazole fatty acid analogue as a PPARα-selective agonist. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 27(18), s. 4059–4068. doi: 10.1016/j.bmc.2019.07.032. Fulltekst i vitenarkiv Vis sammendrag

  The peroxisome proliferator activated receptors (PPARs) are important drug targets in treatment of metabolic and inflammatory disorders. Fibrates, acting as PPARα agonists, have been widely used lipid-lowering agents for decades. However, the currently available PPARα targeting agents show low subtype-specificity and consequently a search for more potent agonists have emerged. In this study, previously isolated oxohexadecenoic acids from the marine algae Chaetoceros karianus were used to design a PPARα-specific analogue. Herein we report the design, synthesis, molecular modelling studies and biological evaluations of the novel 3,5-disubstituted isoxazole analogue 6-(5-heptyl-1,2-oxazol-3-yl)hexanoic acid (1), named ADAM. ADAM shows a clear receptor preference and significant dose-dependent activation of PPARα (EC50 = 47 µM) through its ligand-binding domain (LBD). Moreover, ADAM induces expression of important PPARα target genes, such as CPT1A, in the Huh7 cell line and primary mouse hepatocytes. In addition, ADAM exhibits a moderate ability to regulate PPARγ target genes and drive adipogenesis. Molecular modelling studies indicated that ADAM docks its carboxyl group into opposite ends of the PPARα and -γ LBD. ADAM interacts with the receptor-activating polar network of amino acids (Tyr501, His447 and Ser317) in PPARα, but not in PPARγ LBD. This may explain the lack of PPARγ agonism, and argues for a PPARα-dependent adipogenic function. Such compounds are of interest towards developing new lipid-lowering remedies.

• Fosshaug, Linn Elisabeth Lillerud; Colas, Romain A.; Anstensrud, Anne Kristine; Gregersen, Ida; Nymoen, Ståle H. & Sagen, Ellen [Vis alle 15 forfattere av denne artikkelen] (2019). Early increase of specialized pro-resolving lipid mediators in patients with ST-elevation myocardial infarction. EBioMedicine. 46, s. 264–273. doi: 10.1016/j.ebiom.2019.07.024. Fulltekst i vitenarkiv Vis sammendrag

  Background Termination of acute inflammation is an active process orchestrated by lipid mediators (LM) derived from polyunsaturated fatty acids, referred to as specialized pro-resolving mediators (SPM). These mediators also provide novel therapeutic opportunities for treating inflammatory disease. However, the regulation of these molecules following acute myocardial infarction (MI) remains of interest. Methods In this prospective observational study we aimed to profile plasma levels of SPMs in ST-elevation MI (STEMI) patients during the first week following MI. Plasma LM concentrations were measured in patients with STEMI (n = 15) at three time points and compared with stable coronary artery disease (CAD; n = 10) and healthy controls (n = 10). Findings Our main findings were: (i) Immediately after onset of MI and before peak troponin T levels, STEMI patients had markedly increased levels of SPMs as compared with healthy controls and stable CAD patients, with levels of these mediators declining during follow-up. (ii) The increase in SPMs primarily reflected an increase in docosapentaenoic acid- and docosahexaenoic acid-derived protectins. (iii) Several individual protectins were correlated with the rapid increase in neutrophil counts, but not with CRP. (iv) A shift in 5-LOX activity from the leukotriene B4 pathway to the pro-resolving RvTs was observed. Interpretation The temporal regulation of SPMs indicates that resolution mechanisms are activated early during STEMI as part of an endogenous mechanism to initiate repair. Thus strategies to boost the activity and/or efficacy of these endogenous mechanisms may represent novel therapeutic opportunities for treatment of patients with MI.

• Vik, Anders; Hansen, Trond Vidar & Kuda, Ondrej (2019). Synthesis of both enantiomers of the docosahexaenoic acid ester of 13-hydroxyoctadecadienoic acid (13-DHAHLA). Tetrahedron Letters. ISSN 0040-4039. 60(52), s. 151331–151332. doi: 10.1016/j.tetlet.2019.151331. Fulltekst i vitenarkiv Vis sammendrag

  Recently, several different classes of endogenous lipids have been reported that display antidiabetic and anti-inflammatory effects. Due to their minute presence in human samples, access to synthetic material of each enantiomer becomes necessary for exact structural elucidation and extensive biological evaluation. Herein we report the multi-milligram synthesis of both enantiomers of the docosahexaenoic acid ester of 13-hydroxyoctadecadienoic acid (13-DHAHLA) from commercially available starting materials.

• Rasmussen, Jeanne Sønderskov; Tungen, Jørn Eivind; Palmas, Fransesco; Dalli, Jesmond; Serhan, Charles N & Stenstrøm, Yngve H. [Vis alle 7 forfattere av denne artikkelen] (2019). Stereoselective synthesis of MaR2n-3 DPA. Tetrahedron Letters. ISSN 0040-4039. 61(7), s. 151510–151510. doi: 10.1016/j.tetlet.2019.151510. Fulltekst i vitenarkiv
• Tungen, Jørn Eivind; Kristianslund, Renate; Vik, Anders & Hansen, Trond Vidar (2019). Organoselenium Accelerated Bromolactonization Reaction. Journal of Organic Chemistry. ISSN 0022-3263. 84(18), s. 11373–11381. doi: 10.1021/acs.joc.9b01294. Fulltekst i vitenarkiv Vis sammendrag

  A highly efficient and regioselective bromolactonization protocol is reported. The quantitative formation of synthetically versatile bromolactones occurs in the presence of only 0.1 mol % of an organoselenium compound, coined DECAD herein, within 90 min. DECAD is conveniently prepared on multigram scale from cheap racemic camphor. The presented protocol was easy to scale up and performed equally well on gram scale. Investigation of the mechanism revealed that DECAD forms a selenonium ylene in situ.

• Nesman, Jannicke Irina; Primdahl, Karoline Gangestad; Tungen, Jørn Eivind; Palmas, Fransesco; Dalli, Jesmond & Hansen, Trond Vidar (2019). Synthesis, Structural Confirmation, and Biosynthesis of 22-OH-PD1n-3 DPA. Molecules. ISSN 1431-5157. 24(18). doi: 10.3390/molecules24183228. Fulltekst i vitenarkiv Vis sammendrag

  PD1n-3 DPA belongs to the protectin family of specialized pro-resolving lipid mediators. The protectins are endogenously formed mediators that display potent anti-inflammatory properties and pro-resolving bioactivities and have attracted interest in drug discovery. However, few studies have been reported of the secondary metabolism of the protectins. To investigate the metabolic formation of the putative C22 mono-hydroxylated product, coined 22-OH-PD1n-3 DPA, a stereoselective synthesis was performed. LC/MS-MS data of synthetic 22-OH-PD1n-3 DPA matched the data for the biosynthetic formed product. Cellular studies revealed that 22-OH-PD1n-3 DPA is formed from n-3 docosapentaenoic acid in human serum, and we confirmed that 22-OH-PD1n-3 DPA is a secondary metabolite produced by ω-oxidation of PD1n-3 DPA in human neutrophils and in human monocytes. The results reported are of interest for enabling future structure–activity relationship studies and provide useful molecular insight of the metabolism of the protectin class of specialized pro-resolving mediators.

• Nolsøe, Jens Mortansson Jelstrup; Aursnes, Marius; Stenstrøm, Yngve H. & Hansen, Trond Vidar (2019). Some biogenetic considerations regarding the marine natural product (-)-mucosin. Molecules. ISSN 1431-5157. 24:4147(22), s. 1–11. doi: 10.3390/molecules24224147. Fulltekst i vitenarkiv
• Vik, Anders & Hansen, Trond Vidar (2018). Synthetic manipulations of polyunsaturated fatty acids as a convenient strategy for the synthesis of bioactive compounds. Organic and biomolecular chemistry. ISSN 1477-0520. 16(48), s. 9319–9333. doi: 10.1039/c8ob02586j. Fulltekst i vitenarkiv
• Tungen, Jørn Eivind; Aursnes, Marius; Ramon, Sesquile; Colas, Romain A.; Serhan, Charles Nicholas & Olberg, Dag Erlend [Vis alle 9 forfattere av denne artikkelen] (2018). Synthesis of Protectin D1 Analogs: Novel Pro-resolution and Radiotracer Agents. Organic and biomolecular chemistry. ISSN 1477-0520. 16, s. 6818–6823. doi: 10.1039/c8ob01232f. Fulltekst i vitenarkiv
• Frigerio, Federica; Pasqualini, Giulia; Craparotta, Ilaria; Marchini, Sergio; Vliet, Erwin A. van & Foerch, Patrick [Vis alle 17 forfattere av denne artikkelen] (2018). n-3 Docosapentaenoic acid-derived protectin D1 promotes resolution of neuroinflammation and arrests epileptogenesis. Brain. ISSN 0006-8950. 141(11), s. 3130–3143. doi: 10.1093/brain/awy247. Fulltekst i vitenarkiv
• Nolsøe, Jens Mortansson Jelstrup; Antonsen, Simen Gjelseth; Görbitz, Carl Henrik; Hansen, Trond Vidar; Nesman, Jannicke Irina & Kjendseth, Åsmund Røhr [Vis alle 7 forfattere av denne artikkelen] (2018). Total synthesis of (-)-mucosin and revision of structure. Journal of Organic Chemistry. ISSN 0022-3263. 83(24), s. 15066–15076. doi: 10.1021/acs.joc.8b02318. Fulltekst i vitenarkiv Vis sammendrag

  The first total synthesis of (−)-mucosin (6), an unusual marine hydrindane natural product incorporating a prostaglandin-like submotif, has been achieved. As a result of the campaign, three of the four all-carbon stereocenters in the purported structure 1 have been revised. Of particular note is the excellent control over β-chirality in conjugate addition to ester (−)-22 and the facial selectivity in the subsequent protonation of an intermediate silyl ketene acetal.

• Pistorius, Kimberly; Souza, Patricia R.; Matteis, Roberta De; Austin-Williams, Shani; Primdahl, Karoline Gangestad & Vik, Anders [Vis alle 11 forfattere av denne artikkelen] (2018). PDn-3 DPA Pathway Regulates Human Monocyte Differentiation and Macrophage Function. Cell Chemical Biology. ISSN 2451-9456. 25(6), s. 749–760. doi: 10.1016/j.chembiol.2018.04.017. Fulltekst i vitenarkiv
• Stepniewski, Tomasz Maciej; Torrens-Fontanals, Mariona; Rodríguez-Espigares, Ismael; Giorgino, Toni; Primdahl, Karoline Gangestad & Vik, Anders [Vis alle 9 forfattere av denne artikkelen] (2018). Synthesis, molecular modelling studies and biological evaluation of new oxoeicosanoid receptor 1 agonists. Bioorganic & Medicinal Chemistry. ISSN 0968-0896. 26(12), s. 3580–3587. doi: 10.1016/j.bmc.2018.05.036. Fulltekst i vitenarkiv
• Sørvik, Irene Beate; Solum, Eirik Johansson; Labba, Nils Anders; Hansen, Trond Vidar & Paulsen, Ragnhild Elisabeth (2018). Differential effects of some novel synthetic oestrogen analogs on oxidative PC12 cell death caused by serum deprivation. Free radical research. ISSN 1071-5762. 52(2), s. 273–287. doi: 10.1080/10715762.2018.1430363. Fulltekst i vitenarkiv

Se alle arbeider i NVA

• Bathen, Mina; Sigurjónsson, Svanur; Vik, Anders; Guðmundsson, Haraldur Gunnar; Haraldsson, Guðmundur Gunnar & Hansen, Trond Vidar (2026). Synthesis of n-3 Polyunsaturated Docosahexaenoic Acid-Like Methoxylated Ether Lipid. Fulltekst i vitenarkiv
• The, Daniel; Reinertsen, Amalie Føreid; Vik, Anders & Hansen, Trond Vidar (2025). Synthetic Studies Towards RvD1 Analogs. Fulltekst i vitenarkiv
• Høyby, Isak; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2025). Synthetic studies toward 17R-docosahexaenoic acid. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2025). Synthesis and biosynthesis of protectins: Leads in resolution pharmacology. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2025). Stereoselective synthesis and biology of resolvin E4. Fulltekst i vitenarkiv
• Bathen, Mina; Ervik, Karina; Gani, Osman & Hansen, Trond Vidar (2025). Synthesis of Lipoxin A4 analogues. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2024). Specialized pro-resolving mediators as leads for resolution pharmacology targeting vector borne diseases. Fulltekst i vitenarkiv
• Amundrød, Kristian; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2024). Synthetic Studies Towards RvD1n-3 DPA Analogs. Fulltekst i vitenarkiv
• Büsser, Jonathan; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2024). Synthetic Studies Towards an Analogue of the SPM RvD1n-3 DPA. Fulltekst i vitenarkiv
• Reinertsen, Amalie Føreid; Hansen, Trond Vidar; Nuruddin, Syed Mohammad & Serhan, Charles N (2024). Stereoselective Synthesis and Biological Evaluations of Pro-resolution and Radiotracer Agents. Fulltekst i vitenarkiv
• Bathen, Mina; Vik, Anders & Hansen, Trond Vidar (2024). Synthetic studies towards 4S,5S-dihydroxy docosapentaenoic acid. Fulltekst i vitenarkiv
• Bathen, Mina; Vik, Anders & Hansen, Trond Vidar (2024). Synthetic efforts towards 4S,5S-dihydroxy docosapentaenoic acid. Fulltekst i vitenarkiv
• Bathen, Mina; Vik, Anders & Hansen, Trond Vidar (2024). Synthetic studies towards 4S,5S-dihydroxy docosapentaenoic acid. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2023). Biosynthesis, bioactions and biomedical applications of the protectins: New leads in resolution pharmacology. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2023). Stereoselective Synthesis of Spesialised Pro-Resolving Mediators (SPMs) Using the sp3-sp3 Negishi Reaction. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2023). Stereoselective Synthesis of Sesquiterpenoids Using Organocatalyzed Halocyclization Reactions. Fulltekst i vitenarkiv
• Ervik, Karina; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2023). Total synthesis of the specialized pro-resolving mediator RvD5n-3 DPA. Fulltekst i vitenarkiv
• Ervik, Karina; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2023). Synthetic studies towards the specialized pro-resolving mediator RvD5n-3 DPA. Fulltekst i vitenarkiv
• Haatveit, Åsmund Stenvik; Bathen, Mina; Hansen, Trond Vidar & Vik, Anders (2023). Synthetic studies toward 4S,5S-dihydroxy docosapentaenoic acid. Fulltekst i vitenarkiv
• Bathen, Mina; Haatveit, Åsmund Stenvik; Vik, Anders & Hansen, Trond Vidar (2023). Synthetic studies towards 4S,5S-dihydroxy docosapentaenoic acid. Fulltekst i vitenarkiv
• Nsowah, Samuel Kwame Opoku; Vik, Anders & Hansen, Trond Vidar (2023). Synthesis of New Analogs of 2-Methoxyestradiol. Fulltekst i vitenarkiv
• Bjørndal, Emma; Cong, Victoria; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2023). Synthetic Studies Towards the Specialized Pro-resolving Mediator RvD1n-3 DPA Analogs. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2023). Biosynthesis, bioactions and biomedical applications of the protectins: New leads in resolution pharmacology. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2022). Synthesis and biological evaluations of n-3 DPA derived specialized pro-resolving mediators. Fulltekst i vitenarkiv
• Ervik, Karina; Reinertsen, Amalie Føreid & Hansen, Trond Vidar (2022). Synthetic studies towards the specialized pro-resolving mediator RvD5n-3 DPA. Fulltekst i vitenarkiv
• Vik, Anders; Halvorsen, Trine Grønhaug; Primdahl, Karoline Gangestad; Hansen, Trond Vidar; Wangensteen, Helle & Reubsaet, Leon [Vis alle 7 forfattere av denne artikkelen] (2022). Grunnkurs i farmasøytisk kjemi på UiO moderniseres kontinuerlig. Norsk Farmaceutisk Tidsskrift (NFT). ISSN 0029-1935. s. 33–34. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2022). Nobelprisen i kjemi 2022. [Radio]. NRK. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2022). Nobelprisen i kjemi gikk til klikk-kjemi og bioortogonal kjemi. Kjemi. ISSN 0023-1983. s. 18–22. Fulltekst i vitenarkiv
• Hansen, Trond Vidar; Stenstrøm, Yngve H.; Carlson, Rolf & Sydnes, Leiv K. (2022). Professor Tomáš Hudlický — in Memoriam. Kjemi. ISSN 0023-1983. s. 23–25. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2022). The Nobel Price in Chemistry 2022: Click Chemistry and Bioorthogonal Chemistry. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2022). Nobelprisen i Kjemi 2022: Klikk kjemi og bioortogonal kjemi. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2022). Biosynthesis, bioactions and biomedical applications of the protectins: New leads in resolution pharmacology. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2022). Biosynthesis, bioactions and biomedical applications of the protectins: New leads in resolution pharmacology. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2021). Biosynthetic Pathways of Protectins. Fulltekst i vitenarkiv
• Stenstrøm, Yngve H.; Antonsen, Simen Gjelseth; Nolsøe, Jens Mortansson Jelstrup; Hansen, Trond Vidar; Nicolaisen, Steinar Sollien & Stillerud, Marianne (2020). Synthesis of 5S,6S-dihydroxy Eicosaentaenoic acid by stereoselective hydrolysis of epoxide. Fulltekst i vitenarkiv
• Lerstad, Nora Dotterud; Reinertsen, Amalie Føreid; Tungen, Jørn Eivind & Hansen, Trond Vidar (2020). Synthetic Studies Towards an Analog of RvD1n-3 DPA. Fulltekst i vitenarkiv
• Reinertsen, Amalie Føreid; Tungen, Jørn Eivind; Vik, Anders & Hansen, Trond Vidar (2019). Synthetic Studies Towards an Analogue of RvD1n-3 DPA. Fulltekst i vitenarkiv Vis sammendrag

  Specialized pro-resolving lipid mediators (SPMs) are biosynthesized from n-3 polyunsaturated fatty acids during the resolution phase of acute inflammation.1,2 These molecules are shown to limit further neutrophil recruitment to the inflammatory sites, accelerate the termination of inflammation, shorten the resolution time in vivo and increase the clearance of bacteria and apoptotic cells.2 The SPMs have attracted a great interest as lead compounds in drug discovery programs towards the development of new classes of drugs that dampen inflammation without interfering with the immune response. In 2013, the SPM RvD1n-3 DPA was reported.1 RvD1n-3 DPA displays potent in vivo anti-inflammatory and pro-resolution effects in the low nanomolar range.1 This SPM is an excellent biotemplate for the development of new, small molecular anti-inflammatory drugs and immunoresolvents.3,4 Such simpler analogues are currently in development in our group. 1. Dalli, J.; Colas, R. A.; Serhan, C. N. Sci. Rep. 2013, 3, 1940. 2. Serhan, C. N.; Petasis, N. A. Chem. Rev. 2011, 111, 5922. 3. (a) Serhan, N. A. Nature 2014, 510, 92. (b) Fullerton, J. N.; Gilroy, D.W. Nat. Rev. Drug Discov. 2016, 15, 551. 4. (a) Serhan, C. N, FASEB J. 2017, 31, 1273. (b) Serhan, C. N.; Chiang, N. Curr. Opin. Pharmacol. 2013, 13, 632.

• Rasmussen, Jeanne Sønderskov; Tungen, Jørn Eivind; Vik, Anders; Hansen, Trond Vidar & Stenstrøm, Yngve H. (2019). Synthetic Studies Towards MaR2n-3 DPA. Fulltekst i vitenarkiv Vis sammendrag

  In the last two decades it has been known that specialized pro-resolving mediators (SPMs), biosynthesized from n-3 PUFAs, play an important role in stimulating the return of inflamed tissue to homeostasis.1 There has therefore been a great interest in using these endogenously formed SPMs as lead compounds in drug discovery programs towards the development of new classes of anti-inflammatory drugs. Our group has synthesized MaR1n-3 DPA2 as well as several other SPMs.3 The poster will present our initial synthetic efforts towards the n-3 DPA derived SPM MaR2n-3 DPA (1). 1. Serhan, C. N. Nature 2014, 510, 92–101. 2. Tungen, J. E.; Aursnes, M.; Dalli, J.; Arnardottir, H.; Serhan, C. N.; Hansen, T. V. Chem. Eur. J. 2014, 20, 14575–14578.

• Kristianslund, Renate; Tungen, Jørn Eivind; Vik, Anders & Hansen, Trond Vidar (2019). An Organoselenium Accelerated Bromolactonization Reaction. Fulltekst i vitenarkiv
• Vik, Anders; Primdahl, Karoline Gangestad; Aursnes, Marius; Walker, Mary E.; Colas, Romain A. & Serhan, Charles Nicholas [Vis alle 8 forfattere av denne artikkelen] (2019). Biosynthetic Studies of RvT1-4: A Novel Class of Specialized Pro-resolving and Anti-inflammatory Mediators. Fulltekst i vitenarkiv
• Primdahl, Karoline Gangestad; Tungen, Jørn Eivind; Souza, Patrica R. S De; Colas, Romain A.; Dalli, Jesmond & Hansen, Trond Vidar [Vis alle 7 forfattere av denne artikkelen] (2019). Stereocontrolled Synthesis and Investigation of The Biosynthetic Transformations of 16(S),17(S)-epoxy-PDn-3 DPA. Fulltekst i vitenarkiv
• Tungen, Jørn Eivind; Gerstmann, Lisa; Vik, Anders; Kalesse, Markus; Dalli, Jesmond & Chiang, Nan [Vis alle 8 forfattere av denne artikkelen] (2019). Stereoselective Synthesis and Biological Evaluations of RvD1n-3 DPA. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2019). Synthesis and Biology of Specialized Pro-resolving Mediators. Fulltekst i vitenarkiv
• Nolsøe, Jens Mortansson Jelstrup; Stenstrøm, Yngve H.; Antonsen, Simen Gjelseth; Hansen, Trond Vidar; Røhr, Åsmund Kjendseth & Nesman, Jannicke Irina [Vis alle 8 forfattere av denne artikkelen] (2019). Total Synthesis of (−)-Mucosin and Structural Revision. Fulltekst i vitenarkiv
• Stillerud, Marianne; Antonsen, Simen Gjelseth; Nolsøe, Jens Mortansson Jelstrup; Stenstrøm, Yngve H. & Hansen, Trond Vidar (2019). Synthesis of 5S,6S-dihydroxyeicosapentaenoic acid and 4S,5S-dihydroxydocosahexaenoic acid. Fulltekst i vitenarkiv
• Ellefsen, Christiane Færestrand; Johansson, Silje. J. R; Johannessen, Tonje; Ristun, Mali Schulstad; Antonsen, Simen Gjelseth & Nolsøe, Jens Mortansson Jelstrup [Vis alle 8 forfattere av denne artikkelen] (2019). Synthesis of Fatty Acid Amides. Fulltekst i vitenarkiv
• Gaulin, Malene; Antonsen, Simen Gjelseth; Nolsøe, Jens Mortansson Jelstrup; Hansen, Trond Vidar & Stenstrøm, Yngve H. (2019). Synthesis of analogues of 2-methoxyestradiol with presumed anti-cancer effects. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2019). Biosynthesis, Bioactions and Biomedical Applications of the Protectins. Fulltekst i vitenarkiv
• Nesman, Jannicke Irina; Primdahl, Karoline Gangestad; Tungen, Jørn Eivind; Vik, Anders; Dalli, Jesmond & Hansen, Trond Vidar (2019). Total Synthesis and Biological Evaluations of 22-OH PD1n-3 DPA. Fulltekst i vitenarkiv
• Johnsen, Lars-Inge Gammelsæter; Bero, Rawan; Tungen, Jørn Eivind; Vik, Anders & Hansen, Trond Vidar (2019). Synthetic studies towards 10-keto-DeH-PD1. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2018). Stereoselective Synthesis and Biological Evaluations of RvD1n-3 DPA. Fulltekst i vitenarkiv Vis sammendrag

  Specialized pro-resolving mediators (SPMs) display very potent anti-inflammatory and pro-resolving agonists effects towards G protein-coupled receptors (GPRs) [1]. The resolution of inflammation is now recognized to be an active process strictly regulated by individual families of SPMs and is therefore seen as a biomedical paradigm shift [2]. SPMs are stereoselectively biosynthesized from -3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and docosapentaenoic acid (n-3 DPA), in the presence of lipoxygenases and cyclooxygenase-2 [1]. The first total synthesis of the specialized pro-resolving mediator RvD1n-3 DPA [3] has been achieved using the underutilized sp3-sp3 Negishi cross coupling reaction and an alkyne hydrosilylation-protodesilylation protocol. The LC-MS/MS results of the synthetic material matched those of endogenously produced RvD1n-3 DPA allowing assignment of the absolute configuration of this lipid mediator. Biological evaluations revealed that this novel mediator displays low nanomolar pro-resolving properties in vivo and potently activates the GPR32 receptor. As such, this natural product is of interest as a lead compound towards developing novel immunoresolvents as putative new anti-inflammatory drugs [2,4]. Acknowledgement: We want to express our sincere gratitude towards COST CM1407 for financial support for a STSM scholarship to Lisa Gerstmann form Hannover, Germany to Oslo, Norway. References: [1] Serhan C.N. (2014). Nature 510: 92. [2] Fullerton J.N., Gilroy, D.W. (2016). Nat. Rev. Drug. Discov. 15: 551. [3] Dalli J., Colas R.A., Serhan C.N. (2013). Sci. Rep. 3: 1940. [4] (a) Vik A., Dalli J., Hansen T.V. (2017). Bioorg. Med. Chem. Lett. 27: 2259. (b) Serhan C.N. (2017). FASEB J. 31: 1273.

• Antonsen, Simen Gjelseth; Nolsøe, Jens Mortansson Jelstrup; Stenstrøm, Yngve H.; Hansen, Trond Vidar; Røhr, Åsmund Kjendseth & Nesman, Jannicke Irina [Vis alle 8 forfattere av denne artikkelen] (2018). Total Synthesis of (−)-Mucosin and Structural Revision. Fulltekst i vitenarkiv
• Nolsøe, Jens Mortansson Jelstrup; Antonsen, Simen Gjelseth; Nesman, Jannicke Irina; Hansen, Trond Vidar; Stenstrøm, Yngve H. & Görbitz, Carl Henrik [Vis alle 8 forfattere av denne artikkelen] (2018). Total Synthesis of (−)-Mucosin and Structural Revision. Fulltekst i vitenarkiv
• Primdahl, Karoline Gangestad; Tungen, Jørn Eivind; Souza, Patricia R.S De; Colas, Romain A.; Dalli, Jesmond & Hansen, Trond Vidar [Vis alle 7 forfattere av denne artikkelen] (2018). Stereocontrolled Synthesis and Investigation of the Biosynthetic Transformations of 16(S),17(S)-epoxy-PDn-3 DPA. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2018). Stereoselective Total Synthesis of SPMs Using the sp3-sp3 Negishi Reaction. Fulltekst i vitenarkiv
• Hansen, Trond Vidar (2018). Stereoselective Total Synthesis and Biological Evaluations of Specialized Pro-resolving Mediators and Sesquiterpenoids: Novel Leads in Drug Discovery. Fulltekst i vitenarkiv
• Hansen, Trond Vidar; Ekeberg, Dag & Høiby, Isak (2025). Stereoselective synthesis of the methyl ester of 17R-HDHA. Norges miljø- og biovitenskapelige universitet (NMBU). Fulltekst i vitenarkiv

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