- Rational improvement of the synthesis of 1-deazariboflavin
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The cofactor forms of riboflavin (FMN and FAD) play a crucial role in the mediation of both enzymatic processes and light perception by photo-sensitive proteins, and thus structural analogues of this chromophore are highly useful tools to assist in the elucidation of enzymatic mechanisms. 1-Deazariboflavin has been rarely utilised for this purpose, due in part to its previously difficult and inefficient synthesis. Recent examination has enabled a remarkable improvement in the overall synthetic yield from 11.0 to 61.3%, allowing reliable production of 1-deazariboflavin for use as a tool in enzymatic mechanistic determination.
- Wood, Andrew C.,Knight, David W.,Richter, Gerald
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- Conversion of a Dehalogenase into a Nitroreductase by Swapping its Flavin Cofactor with a 5-Deazaflavin Analogue
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Natural and engineered nitroreductases have rarely supported full reduction of nitroaromatics to their amine products, and more typically, transformations are limited to formation of the hydroxylamine intermediates. Efficient use of these enzymes also requires a regenerating system for NAD(P)H to avoid the costs associated with this natural reductant. Iodotyrosine deiodinase is a member of the same structural superfamily as many nitroreductases but does not directly consume reducing equivalents from NAD(P)H, nor demonstrate nitroreductase activity. However, exchange of its flavin cofactor with a 5-deazaflavin analogue dramatically suppresses its native deiodinase activity and leads to significant nitroreductase activity that supports full reduction to an amine product in the presence of the convenient and inexpensive NaBH4.
- Su, Qi,Boucher, Petrina A.,Rokita, Steven E.
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supporting information
p. 10862 - 10866
(2017/08/30)
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- Synthesis of 2-Alkoxy/Thioalkoxy Benzo[d]imidazoles and 2-Thione Benzo[d]imidazoles via a Phase-Based, Chemoselective Reaction
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2-Alkoxy/thioalkoxy benzo-[d]-imidazole and 2-thione benzo-[d]-imidazole libraries were constructed in solution phase and on solid phase, respectively. The key step in this work is the phase-based chemoselective reaction of the 2-mercaptobenzo-[d]-imidazole intermediate with benzyl chloride (solution phase) and Merrifield resin (solid phase). In the solution-phase case, benzyl chloride reacted with the thiol group of 2-mercaptobenzo-[d]-imidazole, whereas in the solid-phase case, Merrifield resin was introduced at an internal amine group of benzo-[d]-imidazole. To afford the desired 2-alkoxy/thioalkoxy benzo-[d]-imidazole analogues, we used various alkyl halides, alcohols, and thiols in solution phase, and to obtain 2-thione benzo-[d]-imidazole derivatives on solid phase, we used diverse alkyl halides and boronic acids. Finally, to measure the drug potential to be orally active and the molecular diversity in three-dimensional (3D) space, we calculated physicochemical properties and displayed energy-minimized 3D structures. As a result, the libraries from solution phase and solid phase show distinct features in physicochemical properties and skeletal diversities in 3D space.
- Yoon, Hyo-Jeong,Yang, Seung-Ju,Gong, Young-Dae
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supporting information
p. 738 - 747
(2017/12/18)
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- Synthesis of substituted 8-aminoquinolines and phenanthrolines through a Povarov approach
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The synthesis of 8-aminoquinolines and 1,10-phenanthrolines with substituents in α of the nitrogen has been performed through an inverse-demanding aza-Diels-Alder (Povarov reaction) in the fluoroalcohols TFE or HFIP. This path involves simple starting materials: 1,2-phenylenediamines, enol ethers and aldehydes.
- De, Kavita,Legros, Julien,Crousse, Benoit,Chandrasekaran, Srinivasan,Bonnet-Delpon, Daniele
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supporting information; experimental part
p. 347 - 350
(2011/02/26)
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- Synthesis and electrochemical properties of structurally modified flavin compounds
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Four structurally modified flavin compounds have been synthesized and characterized for their redox potential by chemical reduction with sodium dithionite. Besides the previously reported 1- and 5-deazariboflavin, a 7,8-didemethyl derivative and an 8-isopropylriboflavin have been obtained. The synthesis of these compounds started in all cases from appropriately substituted anilines that were condensed with the ribityl chain, followed by completion of the annealed three-ring structure. The didemethyl- and the isopropyl compounds gave absorption maxima similar to riboflavin (436 and 448 nm, respectively), whereas 1-deazariboflavin showed a bathochromically shifted absorption (λmax = 537 nm), and that of 5-deazariboflavin was hypsochromically shifted (λmax = 400 nm). The midpoint potentials (E0′) of the four modified flavin compounds were determined by potentiometric titration, using riboflavin as a reference compound. Both alkyl-modified flavins showed slightly less negative midpoint potentials, whereas both deaza compounds had more negative midpoint values compared to the reference compound. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Mansurova, Madina,Koay, Melissa S.,Gaertner, Wolfgang
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supporting information; experimental part
p. 5401 - 5406
(2009/05/07)
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- Improved Chemical Syntheses of 1- and 5-Deazariboflavin
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The cofactor flavin adenine dinucleotide (FAD) is required for the catalytic activity of a large class of enzymes known as flavoenzymes. Because flavin cofactors participate in catalysis via a number of different mechanisms, isoalloxazine analogues are valuable for mechanistic studies. We report improved chemical syntheses for the preparation of the two key analogues, 5-deazariboflavin and 1-deazariboflavin.
- Carlson, Erin E.,Kiessling, Laura L.
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p. 2614 - 2617
(2007/10/03)
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- Formation of the dimethylbenzimidazole ligand of coenzyme B12 under physiological conditions by a facile oxidative cascade
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(Matrix presented) Dimethylbezimidazole, the axial ligand of vitamin B 12, is synthesized from riboflavin by a two-electron oxidation, a retro-aldol condensation, and a second two-electron oxidation. This oxidative cascade readily takes place nonenzymatically under physiological conditions.
- Maggio-Hall, Lori A.,Dorrestein, Pieter C.,Escalante-Semerena, Jorge C.,Begley, Tadhg P.
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p. 2211 - 2213
(2007/10/03)
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