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Dong Wook Kim - One of the best experts on this subject based on the ideXlab platform.
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an efficient synthesis of 18f fluoropropyl quinoline 5 8 diones by rapid radiofluorination Oxidative Demethylation
Tetrahedron, 2011Co-Authors: Kalme Sachin, Hwan-jeong Jeong, Seok Tae Lim, Myung-hee Sohn, Dae Yoon Chi, Dong Wook KimAbstract:Abstract Since many molecules bearing quinoline-5,8-dione or fused 1,4-quinone moieties possess a wide spectrum of biological activities, efficient methods for incorporation of fluorine-18 (F-18) into quinoline-5,8-diones have received considerable attention in positron emission tomography (PET) molecular imaging studies. In this paper, we describe an efficient synthetic route for the regioselective preparation of fluoropropyl-substituted quinoline-5,8-diones on the C3, C4, and C6 positions by tert-alcohol media fluorination, followed by Oxidative Demethylation of the corresponding dimethoxy compound using N-bromosuccinimide (NBS) in the presence of catalytic amounts of sulfuric acid. Moreover, F-18 labeled [18F]fluoropropylquinoline-5,8-diones [18F]21–23 were prepared from the corresponding mesylate precursors by a method of rapid and efficient one-pot, two-step reactions: radiofluorination using TBA [18F]F generated under no-carrier-added (NCA) conditions; Oxidative Demethylation, resulting in a 45% radiochemical yield of [18F]21–23 (decay-corrected) with a total synthesis time (including HPLC purification) of 75 min and high radiochemical purity (>99%), as well as high specific activity (∼230 GBq/μmol).
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An efficient synthesis of ([18F]fluoropropyl)quinoline-5,8-diones by rapid radiofluorination―Oxidative Demethylation
Tetrahedron, 2011Co-Authors: Kalme Sachin, Hwan-jeong Jeong, Seok Tae Lim, Myung-hee Sohn, Dae Yoon Chi, Dong Wook KimAbstract:Abstract Since many molecules bearing quinoline-5,8-dione or fused 1,4-quinone moieties possess a wide spectrum of biological activities, efficient methods for incorporation of fluorine-18 (F-18) into quinoline-5,8-diones have received considerable attention in positron emission tomography (PET) molecular imaging studies. In this paper, we describe an efficient synthetic route for the regioselective preparation of fluoropropyl-substituted quinoline-5,8-diones on the C3, C4, and C6 positions by tert-alcohol media fluorination, followed by Oxidative Demethylation of the corresponding dimethoxy compound using N-bromosuccinimide (NBS) in the presence of catalytic amounts of sulfuric acid. Moreover, F-18 labeled [18F]fluoropropylquinoline-5,8-diones [18F]21–23 were prepared from the corresponding mesylate precursors by a method of rapid and efficient one-pot, two-step reactions: radiofluorination using TBA [18F]F generated under no-carrier-added (NCA) conditions; Oxidative Demethylation, resulting in a 45% radiochemical yield of [18F]21–23 (decay-corrected) with a total synthesis time (including HPLC purification) of 75 min and high radiochemical purity (>99%), as well as high specific activity (∼230 GBq/μmol).
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Facile oxidation of fused 1,4-dimethoxybenzenes to 1,4-quinones using NBS: fine-tuned control over bromination and oxidation reactions.
Organic letters, 2001Co-Authors: Dong Wook Kim, Han Young Choi, Kee-jung Lee, Dae Yoon ChiAbstract:[figure: see text] Fused 1,4-dimethoxybenzenes could be oxidized to benzoquinones by either direct oxidation or Demethylation-oxidation. The Oxidative Demethylation of 5,8-dimethoxy-2-methylquinoline using 1.1 equiv of NBS in aqueous THF and a catalytic amount of H2SO4 at 20 degrees C for 5 min gave 2-methylquinoline-5,8-dione in 98% yield without bromination. Moreover, we can control either bromination or Oxidative Demethylation, or both reactions.
Masanobu Uchiyama - One of the best experts on this subject based on the ideXlab platform.
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One-step Conversion of Levulinic Acid to Succinic Acid Using I_2/t-BuOK System: The Iodoform Reaction Revisited
Scientific Reports, 2017Co-Authors: Ryosuke Kawasumi, Shodai Narita, Kazunori Miyamoto, Ken-ichi Tominaga, Ryo Takita, Masanobu UchiyamaAbstract:The iodoform reaction has long been used as a qualitative test for acetyl and/or ethanol units in organic molecules. However, its synthetic applications are quite limited. Here, we describe a tuned iodoform reaction for Oxidative Demethylation reaction with I_2 and t -BuOK in t -BuOH, in which in situ- generated t -BuOI serves as the chemoselective iodinating agent. This system enables one-step conversion of levulinic acid to succinic acid, a major four-carbon chemical feedstock. This Oxidative Demethylation is also applicable to other compounds containing an acetyl group/ethanol unit, affording the corresponding carboxylic acids in a selective manner.
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One-step Conversion of Levulinic Acid to Succinic Acid Using I2/t-BuOK System: The Iodoform Reaction Revisited.
Scientific reports, 2017Co-Authors: Ryosuke Kawasumi, Shodai Narita, Kazunori Miyamoto, Ken-ichi Tominaga, Ryo Takita, Masanobu UchiyamaAbstract:The iodoform reaction has long been used as a qualitative test for acetyl and/or ethanol units in organic molecules. However, its synthetic applications are quite limited. Here, we describe a tuned iodoform reaction for Oxidative Demethylation reaction with I2 and t-BuOK in t-BuOH, in which in situ-generated t-BuOI serves as the chemoselective iodinating agent. This system enables one-step conversion of levulinic acid to succinic acid, a major four-carbon chemical feedstock. This Oxidative Demethylation is also applicable to other compounds containing an acetyl group/ethanol unit, affording the corresponding carboxylic acids in a selective manner.
Dae Yoon Chi - One of the best experts on this subject based on the ideXlab platform.
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an efficient synthesis of 18f fluoropropyl quinoline 5 8 diones by rapid radiofluorination Oxidative Demethylation
Tetrahedron, 2011Co-Authors: Kalme Sachin, Hwan-jeong Jeong, Seok Tae Lim, Myung-hee Sohn, Dae Yoon Chi, Dong Wook KimAbstract:Abstract Since many molecules bearing quinoline-5,8-dione or fused 1,4-quinone moieties possess a wide spectrum of biological activities, efficient methods for incorporation of fluorine-18 (F-18) into quinoline-5,8-diones have received considerable attention in positron emission tomography (PET) molecular imaging studies. In this paper, we describe an efficient synthetic route for the regioselective preparation of fluoropropyl-substituted quinoline-5,8-diones on the C3, C4, and C6 positions by tert-alcohol media fluorination, followed by Oxidative Demethylation of the corresponding dimethoxy compound using N-bromosuccinimide (NBS) in the presence of catalytic amounts of sulfuric acid. Moreover, F-18 labeled [18F]fluoropropylquinoline-5,8-diones [18F]21–23 were prepared from the corresponding mesylate precursors by a method of rapid and efficient one-pot, two-step reactions: radiofluorination using TBA [18F]F generated under no-carrier-added (NCA) conditions; Oxidative Demethylation, resulting in a 45% radiochemical yield of [18F]21–23 (decay-corrected) with a total synthesis time (including HPLC purification) of 75 min and high radiochemical purity (>99%), as well as high specific activity (∼230 GBq/μmol).
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An efficient synthesis of ([18F]fluoropropyl)quinoline-5,8-diones by rapid radiofluorination―Oxidative Demethylation
Tetrahedron, 2011Co-Authors: Kalme Sachin, Hwan-jeong Jeong, Seok Tae Lim, Myung-hee Sohn, Dae Yoon Chi, Dong Wook KimAbstract:Abstract Since many molecules bearing quinoline-5,8-dione or fused 1,4-quinone moieties possess a wide spectrum of biological activities, efficient methods for incorporation of fluorine-18 (F-18) into quinoline-5,8-diones have received considerable attention in positron emission tomography (PET) molecular imaging studies. In this paper, we describe an efficient synthetic route for the regioselective preparation of fluoropropyl-substituted quinoline-5,8-diones on the C3, C4, and C6 positions by tert-alcohol media fluorination, followed by Oxidative Demethylation of the corresponding dimethoxy compound using N-bromosuccinimide (NBS) in the presence of catalytic amounts of sulfuric acid. Moreover, F-18 labeled [18F]fluoropropylquinoline-5,8-diones [18F]21–23 were prepared from the corresponding mesylate precursors by a method of rapid and efficient one-pot, two-step reactions: radiofluorination using TBA [18F]F generated under no-carrier-added (NCA) conditions; Oxidative Demethylation, resulting in a 45% radiochemical yield of [18F]21–23 (decay-corrected) with a total synthesis time (including HPLC purification) of 75 min and high radiochemical purity (>99%), as well as high specific activity (∼230 GBq/μmol).
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Facile oxidation of fused 1,4-dimethoxybenzenes to 1,4-quinones using NBS: fine-tuned control over bromination and oxidation reactions.
Organic letters, 2001Co-Authors: Dong Wook Kim, Han Young Choi, Kee-jung Lee, Dae Yoon ChiAbstract:[figure: see text] Fused 1,4-dimethoxybenzenes could be oxidized to benzoquinones by either direct oxidation or Demethylation-oxidation. The Oxidative Demethylation of 5,8-dimethoxy-2-methylquinoline using 1.1 equiv of NBS in aqueous THF and a catalytic amount of H2SO4 at 20 degrees C for 5 min gave 2-methylquinoline-5,8-dione in 98% yield without bromination. Moreover, we can control either bromination or Oxidative Demethylation, or both reactions.
Stephen Bell - One of the best experts on this subject based on the ideXlab platform.
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modification of an enzyme biocatalyst for the efficient and selective Oxidative Demethylation of para substituted benzene derivatives
Chemcatchem, 2016Co-Authors: Rebecca R. Chao, Ian C.-k. Lau, James J. De Voss, Stephen BellAbstract:The bacterial CYP199A4 enzyme is able to efficiently oxidise a narrow range of aromatic acids including 4-methoxybenzoic acid. A serine-244 to aspartate variant was identified with enhanced activity for a wide range of para-methoxy substituted benzenes. Substrates in which the acidic benzoic acid moiety is replaced with a phenol and the amide, aldehyde and bromide analogues were all oxidised with high activity by the S244D mutant (PFR > 600 nmol.(nmol-CYP)1.min1) and with turnover numbers of up to 20,000. When the carboxylate moiety was modified to a nitro, ketone, boronic acid, hydroxymethyl or nitrile groups these substrates were also oxidised at significantly higher activity by S244D compared to the WT enzyme. 3,4-Dimethoxybenzaldehyde was selectively Oxidatively demethylated to 3-methoxy-4-hydroxybenzaldehyde by the S244D mutant 84-fold more rapidly than the WT enzyme. CYP199A4 would have applications in the catalytic regioselective Oxidative Demethylation of suitably substituted benzene substrates under mild conditions and in the presence of more Oxidatively sensitive functional groups, such as an aldehyde.
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Modification of an Enzyme Biocatalyst for the Efficient and Selective Oxidative Demethylation of para‐Substituted Benzene Derivatives
ChemCatChem, 2016Co-Authors: Rebecca R. Chao, Ian C.-k. Lau, James J. De Voss, Stephen BellAbstract:The bacterial CYP199A4 enzyme is able to efficiently oxidise a narrow range of aromatic acids including 4-methoxybenzoic acid. A serine-244 to aspartate variant was identified with enhanced activity for a wide range of para-methoxy substituted benzenes. Substrates in which the acidic benzoic acid moiety is replaced with a phenol and the amide, aldehyde and bromide analogues were all oxidised with high activity by the S244D mutant (PFR > 600 nmol.(nmol-CYP)1.min1) and with turnover numbers of up to 20,000. When the carboxylate moiety was modified to a nitro, ketone, boronic acid, hydroxymethyl or nitrile groups these substrates were also oxidised at significantly higher activity by S244D compared to the WT enzyme. 3,4-Dimethoxybenzaldehyde was selectively Oxidatively demethylated to 3-methoxy-4-hydroxybenzaldehyde by the S244D mutant 84-fold more rapidly than the WT enzyme. CYP199A4 would have applications in the catalytic regioselective Oxidative Demethylation of suitably substituted benzene substrates under mild conditions and in the presence of more Oxidatively sensitive functional groups, such as an aldehyde.
Caiguang Yang - One of the best experts on this subject based on the ideXlab platform.
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Iron-Catalyzed Oxidation Intermediates Captured in a DNA Repair Dioxygenase
2016Co-Authors: Guifang Jia, Caiguang Yang, Guanhua Hou, Qing Dai, Wen Zhang, Guanqun Zheng, Qiang CuiAbstract:Mononuclear iron-containing oxygenases conduct a diverse variety of oxidation functions in biology1,2, including the Oxidative Demethylation of methylated nucleic acids and histones3,4. E. coli AlkB is the first such enzyme that was discovered to repair methylated nucleic acids (Fig. 1)5,6, which are otherwise cytotoxic and/or mutagenic. AlkB human homologues are known to play pivotal roles in various processes7–11. Presented here is the first structural characterization of oxidation intermediates for these demethylases. Employing a chemical cross-linking strategy12,13, complexes of AlkB-dsDNA containing 1,N6-etheno adenine (εA), N3-methyl thymine (3-meT), and N3-methyl cytosine (3-meC) were stabilized and crystallized, respectively. Exposing these crystals, grown under anaerobic conditions containing iron(II) and α-ketoglutarate (αKG), to dioxygen initiates oxidation in crystallo (Supplementary Fig. 1). A glycol (from εA) and a hemiaminal (from 3-meT) intermediates are captured; a zwitterionic intermediate (from 3-2 meC) is also proposed, based on crystallographic observations and computational analysis. The observation of these unprecedented intermediates provides direct support for the Oxidative Demethylation mechanism for these demethylases. This study also depicts a general mechanistic view of how a methyl group is Oxidatively removed from different biological substrates. Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research
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Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase
Nature, 2010Co-Authors: Guifang Jia, Caiguang Yang, Xing Jian, Guanhua Hou, Qing Dai, Wen Zhang, Guanqun Zheng, Qiang CuiAbstract:Mononuclear iron-containing oxygenases have many important roles in the cell, including the Demethylation of DNA and histones. These authors crystallized the AlkB oxygenase in complex with various modified DNAs. By growing the crystals under anaerobic conditions and then exposing them to dioxygen to initiate oxidation, two different intermediates were trapped. A third type of intermediate was determined using additional computational analysis. These structures provide insight into how these enzymes perform Oxidative Demethylation. Mononuclear iron-containing oxygenases conduct a diverse variety of oxidation functions in biology^ 1 , 2 , including the Oxidative Demethylation of methylated nucleic acids and histones^ 3 , 4 . Escherichia coli AlkB is the first such enzyme that was discovered to repair methylated nucleic acids^ 5 , 6 , which are otherwise cytotoxic and/or mutagenic. AlkB human homologues are known to play pivotal roles in various processes^ 7 , 8 , 9 , 10 , 11 . Here we present structural characterization of oxidation intermediates for these demethylases. Using a chemical cross-linking strategy^ 12 , 13 , complexes of AlkB–double stranded DNA (dsDNA) containing 1,N^6-etheno adenine (εA), N^3-methyl thymine (3-meT) and N^3-methyl cytosine (3-meC) are stabilized and crystallized, respectively. Exposing these crystals, grown under anaerobic conditions containing iron(II) and α-ketoglutarate (αKG), to dioxygen initiates oxidation in crystallo . Glycol (from εA) and hemiaminal (from 3-meT) intermediates are captured; a zwitterionic intermediate (from 3-meC) is also proposed, based on crystallographic observations and computational analysis. The observation of these unprecedented intermediates provides direct support for the Oxidative Demethylation mechanism for these demethylases. This study also depicts a general mechanistic view of how a methyl group is Oxidatively removed from different biological substrates. The AlkB type proteins are demethylases that are thought to play a part in DNA repair by Oxidatively removing methyl adducts on DNA, RNA and histones. Yi et al . have determined the structure of AlkB oxygenase crystallized in complex with various modified DNAs. By growing the crystals under anaerobic conditions and then exposing them to dioxygen to initiate oxidation, two different intermediates were trapped. A third type of intermediate was determined using additional computational analysis. These structures provide detailed mechanistic insight into how these enzymes perform Oxidative Demethylation.
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a non heme iron mediated chemical Demethylation in dna and rna
Accounts of Chemical Research, 2009Co-Authors: Chengqi Yi, Caiguang Yang, Chuan HeAbstract:DNA methylation is arguably one of the most important chemical signals in biology. However, aberrant DNA methylation can lead to cytotoxic or mutagenic consequences. A DNA repair protein in Escherichia coli, AlkB, corrects some of the unwanted methylations of DNA bases by a unique Oxidative Demethylation in which the methyl carbon is liberated as formaldehyde. The enzyme also repairs exocyclic DNA lesions—that is, derivatives in which the base is augmented with an additional heterocyclic subunit—by a similar mechanism. Two proteins in humans that are homologous to AlkB, ABH2 and ABH3, repair the same spectrum of lesions; another human homologue of AlkB, FTO, is linked to obesity. In this Account, we describe our studies of AlkB, ABH2, and ABH3, including our development of a general strategy to trap homogeneous protein−DNA complexes through active-site disulfide cross-linking. AlkB uses a non-heme mononuclear iron(II) and the cofactors 2-ketoglutarate (2KG) and dioxygen to effect Oxidative Demethylation o...
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A Non-Heme Iron-Mediated Chemical Demethylation in DNA and RNA
Accounts of chemical research, 2009Co-Authors: Caiguang YangAbstract:DNA methylation is arguably one of the most important chemical signals in biology. However, aberrant DNA methylation can lead to cytotoxic or mutagenic consequences. A DNA repair protein in Escherichia coli, AlkB, corrects some of the unwanted methylations of DNA bases by a unique Oxidative Demethylation in which the methyl carbon is liberated as formaldehyde. The enzyme also repairs exocyclic DNA lesions—that is, derivatives in which the base is augmented with an additional heterocyclic subunit—by a similar mechanism. Two proteins in humans that are homologous to AlkB, ABH2 and ABH3, repair the same spectrum of lesions; another human homologue of AlkB, FTO, is linked to obesity. In this Account, we describe our studies of AlkB, ABH2, and ABH3, including our development of a general strategy to trap homogeneous protein−DNA complexes through active-site disulfide cross-linking. AlkB uses a non-heme mononuclear iron(II) and the cofactors 2-ketoglutarate (2KG) and dioxygen to effect Oxidative Demethylation o...
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Oxidative Demethylation of 3 methylthymine and 3 methyluracil in single stranded dna and rna by mouse and human fto
FEBS Letters, 2008Co-Authors: Caiguang Yang, Chengqi Yi, Shangdong Yang, Xing Jian, Zhiqiang Zhou, Chuan HeAbstract:The human obesity susceptibility gene, FTO, encodes a protein that is homologous to the DNA repair AlkB protein. The AlkB family proteins utilize iron(II), α-ketoglutarate (α-KG) and dioxygen to perform Oxidative repair of alkylated nucleobases in DNA and RNA. We demonstrate here the Oxidative Demethylation of 3-methylthymine (3-meT) in single-stranded DNA (ssDNA) and 3-methyluracil (3-meU) in single-stranded RNA (ssRNA) by recombinant human FTO protein in vitro. Both human and mouse FTO proteins preferentially repair 3-meT in ssDNA over other base lesions tested. They showed negligible activities against 3-meT in double-stranded DNA (dsDNA). In addition, these two proteins can catalyze the Demethylation of 3-meU in ssRNA with a slightly higher efficiency over that of 3-meT in ssDNA, suggesting that methylated RNAs are the preferred substrates for FTO.
