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Carlos Kleber Zago De Andrade - One of the best experts on this subject based on the ideXlab platform.
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Preparação de lactonas via formação de ligação carbono-carbono : sinteses formais de (-)-serriconina, (+)-lactona de Prelog-Djerassi e estudos visando a sintese do (+)-10-desoximetinolideo
2017Co-Authors: Carlos Kleber Zago De AndradeAbstract:Resumo: Uma metodologia de obtenção de d-lactonas foi desenvolvida em que substratos, cujos centros assimétricos são controlados por reações de condensação aldólica estereosseletiva, sofrem alquilação intramolecular e o anel lactônico é formado via ligação C-C. Nos estudos iniciais de desenvolvimento da metodologia (capítulo I), lactonas modelos foram obtidas dos substratos 19, 20, 22 e 23. A rota sintética envolveu 5 etapas, com rendimento total na faixa de 38-49%. As melhores condições para a reação de formação das d-lactonas envolveram o uso de enolatos de potássio e o rendimento da ciclização atingiu 78%. A metodologia desenvolvida foi aplicada na síntese de d-lactonas com interesse sintético relevado. Assim, a d-lactona 64, precursora do feromônio serricornina, foi sintetizada em 6 etapas e 26% de rendimento total, empregando-se condensação aldólica com enolatos de boro para o controle dos centros assimétricos (capítulo II). A lactona 166, um equivalente sintético da lactona de Prelog-Djerassi, foi obtida tanto em sua forma racêmica (capítulo lII) quanto quiral (capítulo IV), empregando-se condensação aldólica com sililcetenotioacetais no primeiro caso e enolato de boro no segundo. A lactona 166 racêmica foi obtida em 7 etapas e 25% de rendimento total e a quiral, em 8 etapas e 22% de rendimento total. A lactona 166 quiral obtida na síntese anterior foi usada como intermediário nos estudos realizados de preparação de um dos fragmentos do (+)-10-desoximetinolídeo, aglicona do antibiótico macrolídico (+)-10-desoximetimicina (capítulo V). O outro fragmento, o iodeto vinílico 300, foi obtido em 5 etapas e 26% de rendimento total. Tentativas de acoplamento dos 2 fragmentos foram impossibilitadas pela não obtenção do cetofosfonato 279, necessário para a reação de fechamento do anel macrocíclico (reação de Wittig-Horner). A macrolactona modelo de 12 membros 318 foi obtida por reação intramolecular entre um aldeído e um iodeto vinílico, mediada por Cr/Ni, em 63% de rendimento (capítulo VI). O sucesso desta ciclização possibilita sua utilização na síntese de antibióticos macrolídicos como método alternativo aos métodos até então utilizados.Abstract: A methodology for the preparation of d-Lactones was developed where substrates with asymmetric centers controlled by aldol condensation reactions suffer intramolecular alkylation resulting formation of the lactonic ring via a C-C bonding formation process. ln the initial studies concerning the development of the methodology (chapter I), model Lactones were obtained from substrates 19, 20, 22 and 23. The synthetic route involved 5 steps, with overall yield ranging between 38-49%. The best reaction conditions were achieved with potassium enolates and the cyclization yield was 78%. The developed methodology was applied to the synthesis of relevant d-Lactones. Lactone 64, precursor of the sex pheromone serricornine 36, was prepared in 6 steps and 26% overall yield, employing aldol condensation with boron enolates to assure the correct stereochemistry of the asymmetric centers (chapter lI). Lactone 166, a synthetic equivalent of the Prelog-Djerassi lactonic acid, was obtained either in the racemic (chapter IlI) or chiral form (chapter IV), employing aldol condensation with silyl ketene acetals in the first case and boron enolate in the second case. Racemic 166 was prepared in 7 steps and 25% overall yield and chiral 166 in 8 steps and 22% overall yield. Chiral 166 was explored as a synthetic intermediate in the preparation of the C(1)-C(8) fragment of (+)-10-desoxymethynolide, aglicon of the macrolide antibiotic (+)-10-desoxymethymicyn (chapter V). Vinyl iodide 300, the C(9)-C(13) fragment, was obtained in 5 steps and 26% overall yield. Coupling of these 2 fragments was not possible due to the difficulties in the preparation of ketophosphonate 279, the ultimate precursor for the postulated macrocyclization via a Wittig-Horner reaction. The 12-membered model macroLactone 318 was obtained via intramolecular reaction between an aldehyde and a vinyl iodide, mediated by Cr/Ni, in 63% yield (chapter V). The success of this cyclization allows one to consider it as an alternative method for the construction of these macrolide antibiotics
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Preparação de lactonas via formação de ligação carbono-carbono : sinteses formais de (-)-serriconina, (+)-lactona de Prelog-Djerassi e estudos visando a sintese do (+)-10-desoximetinolideo
Universidade Estadual de Campinas . Instituto de Quimica, 1996Co-Authors: Carlos Kleber Zago De AndradeAbstract:Uma metodologia de obtenção de d-lactonas foi desenvolvida em que substratos, cujos centros assimétricos são controlados por reações de condensação aldólica estereosseletiva, sofrem alquilação intramolecular e o anel lactônico é formado via ligação C-C. Nos estudos iniciais de desenvolvimento da metodologia (capítulo I), lactonas modelos foram obtidas dos substratos 19, 20, 22 e 23. A rota sintética envolveu 5 etapas, com rendimento total na faixa de 38-49%. As melhores condições para a reação de formação das d-lactonas envolveram o uso de enolatos de potássio e o rendimento da ciclização atingiu 78%. A metodologia desenvolvida foi aplicada na síntese de d-lactonas com interesse sintético relevado. Assim, a d-lactona 64, precursora do feromônio serricornina, foi sintetizada em 6 etapas e 26% de rendimento total, empregando-se condensação aldólica com enolatos de boro para o controle dos centros assimétricos (capítulo II). A lactona 166, um equivalente sintético da lactona de Prelog-Djerassi, foi obtida tanto em sua forma racêmica (capítulo lII) quanto quiral (capítulo IV), empregando-se condensação aldólica com sililcetenotioacetais no primeiro caso e enolato de boro no segundo. A lactona 166 racêmica foi obtida em 7 etapas e 25% de rendimento total e a quiral, em 8 etapas e 22% de rendimento total. A lactona 166 quiral obtida na síntese anterior foi usada como intermediário nos estudos realizados de preparação de um dos fragmentos do (+)-10-desoximetinolídeo, aglicona do antibiótico macrolídico (+)-10-desoximetimicina (capítulo V). O outro fragmento, o iodeto vinílico 300, foi obtido em 5 etapas e 26% de rendimento total. Tentativas de acoplamento dos 2 fragmentos foram impossibilitadas pela não obtenção do cetofosfonato 279, necessário para a reação de fechamento do anel macrocíclico (reação de Wittig-Horner). A macrolactona modelo de 12 membros 318 foi obtida por reação intramolecular entre um aldeído e um iodeto vinílico, mediada por Cr/Ni, em 63% de rendimento (capítulo VI). O sucesso desta ciclização possibilita sua utilização na síntese de antibióticos macrolídicos como método alternativo aos métodos até então utilizados.A methodology for the preparation of d-Lactones was developed where substrates with asymmetric centers controlled by aldol condensation reactions suffer intramolecular alkylation resulting formation of the lactonic ring via a C-C bonding formation process. ln the initial studies concerning the development of the methodology (chapter I), model Lactones were obtained from substrates 19, 20, 22 and 23. The synthetic route involved 5 steps, with overall yield ranging between 38-49%. The best reaction conditions were achieved with potassium enolates and the cyclization yield was 78%. The developed methodology was applied to the synthesis of relevant d-Lactones. Lactone 64, precursor of the sex pheromone serricornine 36, was prepared in 6 steps and 26% overall yield, employing aldol condensation with boron enolates to assure the correct stereochemistry of the asymmetric centers (chapter lI). Lactone 166, a synthetic equivalent of the Prelog-Djerassi lactonic acid, was obtained either in the racemic (chapter IlI) or chiral form (chapter IV), employing aldol condensation with silyl ketene acetals in the first case and boron enolate in the second case. Racemic 166 was prepared in 7 steps and 25% overall yield and chiral 166 in 8 steps and 22% overall yield. Chiral 166 was explored as a synthetic intermediate in the preparation of the C(1)-C(8) fragment of (+)-10-desoxymethynolide, aglicon of the macrolide antibiotic (+)-10-desoxymethymicyn (chapter V). Vinyl iodide 300, the C(9)-C(13) fragment, was obtained in 5 steps and 26% overall yield. Coupling of these 2 fragments was not possible due to the difficulties in the preparation of ketophosphonate 279, the ultimate precursor for the postulated macrocyclization via a Wittig-Horner reaction. The 12-membered model macroLactone 318 was obtained via intramolecular reaction between an aldehyde and a vinyl iodide, mediated by Cr/Ni, in 63% yield (chapter V). The success of this cyclization allows one to consider it as an alternative method for the construction of these macrolide antibiotics
Kokgan Chan - One of the best experts on this subject based on the ideXlab platform.
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Labrenzia sp. BM1: A Quorum Quenching Bacterium That Degrades N-acyl Homoserine Lactones via Lactonase Activity
Sensors (Basel Switzerland), 2014Co-Authors: Norshazliza Ab Ghani, Wai-fong Yin, Siti Nur Maisarah Norizan, Xin Yue Chan, Kokgan ChanAbstract:We report the degradation of quorum sensing N-acylhomoserine Lactone molecules by a bacterium isolated from a Malaysian marine water sample. MALDI-TOF and phylogenetic analysis indicated this isolate BM1 clustered closely to Labrenzia sp. The quorum quenching activity of this isolate was confirmed by using a series of bioassays and rapid resolution liquid chromatography analysis. Labrenzia sp. degraded a wide range of N-acylhomoserine Lactones namely N-(3-hexanoyl)-l-homoserine Lactone (C6-HSL), N-(3-oxohexanoyl)-l-homoserine Lactone (3-oxo-C6-HSL) and N-(3-hydroxyhexanoyl)-l-homoserine Lactone (3-hydroxy-C6-HSL). Re-lactonisation bioassays confirmed Labrenzia sp. BM1 degraded these signalling molecules efficiently via lactonase activity. To the best of our knowledge, this is the first documentation of a Labrenzia sp. capable of degrading N-acylhomoserine Lactones and confirmation of its lactonase-based mechanism of action.
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Detection of Quorum Sensing Activity in the Multidrug-Resistant Clinical Isolate Pseudomonas aeruginosa Strain GB11
MDPI AG, 2014Co-Authors: Huey Jia Cheng, Wai-fong Yin, Yuet Meng Cheong, Wen-si Tan, Kokgan ChanAbstract:A multidrug-resistant clinical bacteria strain GB11 was isolated from a wound swab on the leg of a patient. Identity of stain GB11 as Pseudomonas aeruginosa was validated by using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Detection of the production of signaling molecules, N-acylhomoserine Lactones (AHLs), was conducted using three different bacterial biosensors. A total of four different AHLs were found to be produced by strain GB11, namely N-butyryl homoserine Lactone (C4-HSL), N-hexanoylhomoserine Lactone (C6-HSL), N-octanoyl homoserine Lactone (C8-HSL) and N-3-oxo-dodecanoylhomoserine Lactone (3-oxo-C12-HSL) using high resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). Of these detected AHLs, 3-oxo-C12-HSL was found to be the most abundant AHL produced by P. aeruginosa GB11
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characterization of quorum sensing and quorum quenching soil bacteria isolated from malaysian tropical montane forest
Sensors, 2012Co-Authors: Teik Min Chong, Wai-fong Yin, Chonglek Koh, Choon Kook Sam, Yeunmun Choo, Kokgan ChanAbstract:We report the production and degradation of quorum sensing N-acyl-homoserine Lactones by bacteria isolated from Malaysian montane forest soil. Phylogenetic analysis indicated that these isolates clustered closely to the genera of Arthrobacter, Bacillus and Pseudomonas. Quorum quenching activity was detected in six isolates of these three genera by using a series of bioassays and rapid resolution liquid chromatography analysis. Biosensor screening and high resolution liquid chromatography-mass spectrometry analysis revealed the production of N-dodecanoyl-L-homoserine Lactone (C12-HSL) by Pseudomonas frederiksbergensis (isolate BT9). In addition to degradation of a wide range of N-acyl-homoserine Lactones, Arthrobacter and Pseudomonas spp. also degraded p-coumaroyl-homoserine Lactone. To the best of our knowledge, this is the first documentation of Arthrobacter and Pseudomonas spp. capable of degrading p-coumaroyl-homoserine Lactone and the production of C12-HSL by P. frederiksbergensis.
Kaliappanadar Nellaiappan - One of the best experts on this subject based on the ideXlab platform.
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irreversible inhibition of lysyl oxidase by homocysteine thioLactone and its selenium and oxygen analogues implications for homocystinuria
Journal of Biological Chemistry, 1997Co-Authors: Kaliappanadar Nellaiappan, Herbert M KaganAbstract:Abstract Homocysteine thioLactone, selenohomocysteine Lactone, and homoserine Lactone were found to be competitive, irreversible inhibitors of lysyl oxidase, with K Ivalues of 21 ± 3 μm, 8.3 ± 2.2 μm, and 420 ± 56 μm, respectively. The first order rate constants for inactivation (k 2) of the enzyme varied over a much smaller range, ranging from 0.12 to 0.18 to 0.28 min−1 for the Se-, thio-, and O-Lactones, respectively. Mutually exclusive labeling of the enzyme by [1-14C]β-aminopropionitrile, [U-14C]phenylhydrazine, or [35S]homocysteine thioLactone was observed. These labeling results, together with the closely similar perturbations of the near UV-visible spectra of lysyl oxidase and of a model of its lysine tyrosylquinone cofactor by the thioLactone, indicate that the Lactones likely derivatize and reduce the active site carbonyl cofactor. Substitution with deuterium at the α-carbon of the thioLactone caused a deuterium kinetic isotope effect onk 2 of 3.2 ± 0.2, consistent with the involvement of rate-limiting α-proton abstraction during Lactone-induced inactivation of the enzyme. The activities of plasma amine oxidase and diamine oxidase were only minimally reduced at concentrations of the sulfur or selenium Lactones that fully inhibited lysyl oxidase. Thus, these Lactones constitute a new category of mechanism-based inactivators selective for lysyl oxidase. Further, these results may relate to the development of connective tissue defects seen in homocystinuria.
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irreversible inhibition of lysyl oxidase by homocysteine thioLactone and its selenium and oxygen analogues implications for homocystinuria
Journal of Biological Chemistry, 1997Co-Authors: Guanmei Liu, Kaliappanadar Nellaiappan, H KaganAbstract:Homocysteine thioLactone, selenohomocysteine Lactone, and homoserine Lactone were found to be competitive, irreversible inhibitors of lysyl oxidase, with KI values of 21 +/- 3 microM, 8.3 +/- 2.2 microM, and 420 +/- 56 microM, respectively. The first order rate constants for inactivation (k2) of the enzyme varied over a much smaller range, ranging from 0.12 to 0.18 to 0.28 min-1 for the Se-, thio-, and O-Lactones, respectively. Mutually exclusive labeling of the enzyme by [1-14C]beta-aminopropionitrile, [U-14C]phenylhydrazine, or [35S]homocysteine thioLactone was observed. These labeling results, together with the closely similar perturbations of the near UV-visible spectra of lysyl oxidase and of a model of its lysine tyrosylquinone cofactor by the thioLactone, indicate that the Lactones likely derivatize and reduce the active site carbonyl cofactor. Substitution with deuterium at the alpha-carbon of the thioLactone caused a deuterium kinetic isotope effect on k2 of 3.2 +/- 0.2, consistent with the involvement of rate-limiting alpha-proton abstraction during Lactone-induced inactivation of the enzyme. The activities of plasma amine oxidase and diamine oxidase were only minimally reduced at concentrations of the sulfur or selenium Lactones that fully inhibited lysyl oxidase. Thus, these Lactones constitute a new category of mechanism-based inactivators selective for lysyl oxidase. Further, these results may relate to the development of connective tissue defects seen in homocystinuria.
Herbert M Kagan - One of the best experts on this subject based on the ideXlab platform.
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irreversible inhibition of lysyl oxidase by homocysteine thioLactone and its selenium and oxygen analogues implications for homocystinuria
Journal of Biological Chemistry, 1997Co-Authors: Kaliappanadar Nellaiappan, Herbert M KaganAbstract:Abstract Homocysteine thioLactone, selenohomocysteine Lactone, and homoserine Lactone were found to be competitive, irreversible inhibitors of lysyl oxidase, with K Ivalues of 21 ± 3 μm, 8.3 ± 2.2 μm, and 420 ± 56 μm, respectively. The first order rate constants for inactivation (k 2) of the enzyme varied over a much smaller range, ranging from 0.12 to 0.18 to 0.28 min−1 for the Se-, thio-, and O-Lactones, respectively. Mutually exclusive labeling of the enzyme by [1-14C]β-aminopropionitrile, [U-14C]phenylhydrazine, or [35S]homocysteine thioLactone was observed. These labeling results, together with the closely similar perturbations of the near UV-visible spectra of lysyl oxidase and of a model of its lysine tyrosylquinone cofactor by the thioLactone, indicate that the Lactones likely derivatize and reduce the active site carbonyl cofactor. Substitution with deuterium at the α-carbon of the thioLactone caused a deuterium kinetic isotope effect onk 2 of 3.2 ± 0.2, consistent with the involvement of rate-limiting α-proton abstraction during Lactone-induced inactivation of the enzyme. The activities of plasma amine oxidase and diamine oxidase were only minimally reduced at concentrations of the sulfur or selenium Lactones that fully inhibited lysyl oxidase. Thus, these Lactones constitute a new category of mechanism-based inactivators selective for lysyl oxidase. Further, these results may relate to the development of connective tissue defects seen in homocystinuria.
H Kagan - One of the best experts on this subject based on the ideXlab platform.
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irreversible inhibition of lysyl oxidase by homocysteine thioLactone and its selenium and oxygen analogues implications for homocystinuria
Journal of Biological Chemistry, 1997Co-Authors: Guanmei Liu, Kaliappanadar Nellaiappan, H KaganAbstract:Homocysteine thioLactone, selenohomocysteine Lactone, and homoserine Lactone were found to be competitive, irreversible inhibitors of lysyl oxidase, with KI values of 21 +/- 3 microM, 8.3 +/- 2.2 microM, and 420 +/- 56 microM, respectively. The first order rate constants for inactivation (k2) of the enzyme varied over a much smaller range, ranging from 0.12 to 0.18 to 0.28 min-1 for the Se-, thio-, and O-Lactones, respectively. Mutually exclusive labeling of the enzyme by [1-14C]beta-aminopropionitrile, [U-14C]phenylhydrazine, or [35S]homocysteine thioLactone was observed. These labeling results, together with the closely similar perturbations of the near UV-visible spectra of lysyl oxidase and of a model of its lysine tyrosylquinone cofactor by the thioLactone, indicate that the Lactones likely derivatize and reduce the active site carbonyl cofactor. Substitution with deuterium at the alpha-carbon of the thioLactone caused a deuterium kinetic isotope effect on k2 of 3.2 +/- 0.2, consistent with the involvement of rate-limiting alpha-proton abstraction during Lactone-induced inactivation of the enzyme. The activities of plasma amine oxidase and diamine oxidase were only minimally reduced at concentrations of the sulfur or selenium Lactones that fully inhibited lysyl oxidase. Thus, these Lactones constitute a new category of mechanism-based inactivators selective for lysyl oxidase. Further, these results may relate to the development of connective tissue defects seen in homocystinuria.
