- Reactivity of Tricarbonyl(pentadienyl)iron(1+) Cations: Enantioselective Synthesis of 5-HETE Methyl Ester
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The syntheses of racemic 5-HETE methyl ester (1) and of 5-HETE lactone (5-HL) were accomplished in 11 steps from tricarbonyliron(1+)hexafluorophosphate (2).A second synthesis of 1 from 2 in five steps was also achieved.Star
- Tao, Chunlin,Donaldson, William A.
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- Synthesis, molecular modelling studies and biological evaluation of new oxoeicosanoid receptor 1 agonists
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The oxoeicosanoid receptor 1 (OXER1) is a member of the G-protein coupled receptors (GPCR) family, and is involved in inflammatory processes and oncogenesis. As such it is an attractive target for pharmacological intervention. The present study aimed to shed light on the molecular fundaments of OXER1 modulation using chemical probes structurally related to the natural agonist 5-oxo-ETE. In a first step, 5-oxo-ETE and its closely related derivatives (5-oxo-EPE and 4-oxo-DHA) were obtained by conducting concise and high-yielding syntheses. The biological activity of obtained compounds was assessed in terms of potency (EC50) and efficacy (Emax) for arrestin recruitment. Finally, molecular modelling and simulation were used to explore binding characteristics of 5-oxo-ETE and derivatives with the aim to rationalize biological activity. Our data suggest that the tested 5-oxo-ETE derivatives (i) insert quickly into the membrane, (ii) access the receptor via transmembrane helices (TMs) 5 and 6 from the membrane side and (iii) drive potency and efficacy by differential interaction with TM5 and 7. Most importantly, we found that the methyl ester of 5-oxo-ETE (1a) showed even a higher maximum response than the natural agonist (1). In contrast, shifting the 5-oxo group into position 4 results in inactive compounds (4-oxo DHA compounds (3) and (3a)). All in all, our study provides relevant structural data that help understanding better OXER1 functionality and its modulation. The structural information presented herein will be useful for designing new lead compounds with desired signalling profiles.
- Stepniewski, Tomasz Maciej,Torrens-Fontanals, Mariona,Rodríguez-Espigares, Ismael,Giorgino, Toni,Primdahl, Karoline G.,Vik, Anders,Stenstr?m, Yngve,Selent, Jana,Hansen, Trond Vidar
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p. 3580 - 3587
(2018/06/06)
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- METHOD OF SYNTHESIZING A 5-OXO-CONJUGATED FATTY ACID
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There is provided a novel chemical synthetic method for the preparation of a 5-oxo-ETE and related compounds. The method is based on a short and efficient synthesis of 5-oxo-ETE from commercially available Arachidonic acid. The method is based on the surprising discovery that a 5-oxo-conjugated fatty acid may be efficiently converted into the corresponding 5-oxo-conjugated fatty acid by reaction with the Dess-Martin reagent (1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one)in the presence of pyridine or a substituted pyridine.
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Page/Page column 9
(2011/11/06)
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- Synthesis of polyconjugated fatty acids
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The present invention relates to fatty acids. In particular, the present invention provides polyconjugated fatty acids, and methods of their synthesis and their use.
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Page 3; 11-12
(2010/02/10)
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- Synthesis of long chain n-3 and n-6 fatty acids having a photoactive conjugated tetraene group
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Fatty acids of the n-3 and n-6 families containing a photoactive conjugated tetraene group near the carboxylate were prepared from several naturally occurring fatty acids by sequential iodolactonization and treatment with excess 1,8-diazabicyclo[5.4.0]undec-7-ene. The new conjugated fatty acids include 5E,7E,9E,11Z,14Z- and 5E,7E,9E,11E,14Z-eicosapentaenoic acids derived from arachidonic acid; 5E,7E,9E,11Z,14Z,17Z- and 5E,7E,9E,11E,14Z,17Z-eicosahexaenoic acids from eicosapentaenoic acid; and 4E,6E,8E,10Z,13Z,16Z,19Z- and 4E,6E,8E,10E,13Z,16Z,19Z-docosaheptaenoic acids from docosahexaenoic acid. All of the newly synthesized fatty acids were characterized by UV, 1H NMR and mass spectroscopy. These new products represent the first examples of directed conjugation of methylene interrupted double bond systems. The products can be synthesized in gram quantities and in high yields (>50%). Interestingly, it did not prove possible to synthesize fatty acids having a triene group near the carboxyl group even using mild conditions and different synthetic approaches. Once initiated, the isomerization always continued until a tetraene group was formed. Because of the sensitivity of the tetraene group to light, these fatty acids have the potential for being used in tracking fatty acid movements in cells employing fluorescence techniques and in UV light-induced cross linking to membrane proteins.
- Kuklev, Dmitry V.,Smith, William L.
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p. 145 - 158
(2007/10/03)
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- FORMATION AND STRUCTURE DETERMINATION OF 5,6-EPOXY-8,11,14-Z-EICOSATRIENOIC ACID AND 5-OXO-8,11,14-Z-EICOSATRIENOIC ACID
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The formation of 5,6-epoxy-8,11,14-Z-eicosatrienoic acid and 5-oxo-8,11,14-Z-eicosatrienoic acid as by-products in the synthesis of 5-hydroxy-6-E-8,11,14-Z-eicosatetraenoic acid is described.
- Spur, Bernd,Crea, Attilio,Peters, Wilfried
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p. 1755 - 1758
(2007/10/02)
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- A PRACTICAL PROCESS FOR LARGE-SCALE SYNTHESIS OF (S)-5-HYDROXY-6-TRANS-8,11,14-CIS-EICOSATETRAENOIC ACID (5-HETE)
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(S)-5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HETE) (1) and its enantiomer are readily available by a chemical synthesis from arachidonic acid which includes a chromatographic separation of diastereomeric urethanes (3) made from (+/-)-5-HETE methyl ester and the isocyanate 4 derived from dehydroabietylamine.
- Corey, E. J.,Hashimoto, Shun-ichi
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p. 299 - 302
(2007/10/02)
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