Pub Date : 2014-12-22DOI: 10.14293/S2199-1006.1.SOR-LIFE.A181CU.v1
Yongfei Yang, Chengyu Liang
Autophagy is an evolutionarily conserved self-digestion process for the quality control of intracellular entities in eukaryotes. In the past few years, mounting evidence indicates that microRNAs (miRNAs)-mediated post-transcriptional regulation of gene expression represents an integral part of the autophagy regulatory network and may have a substantial effect on autophagy-related physiological and pathological conditions including cancer. Herein, we examine some of the molecular mechanisms by which miRNAs manipulate the autophagic machinery to maintain cellular homeostasis and their biological outputs during cancer development. A better understanding of interaction between miRNAs and cellular autophagy may ultimately benefit future cancer diagnostic and anticancer therapeutics.
{"title":"MicroRNAs: an emerging player in autophagy.","authors":"Yongfei Yang, Chengyu Liang","doi":"10.14293/S2199-1006.1.SOR-LIFE.A181CU.v1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-LIFE.A181CU.v1","url":null,"abstract":"Autophagy is an evolutionarily conserved self-digestion process for the quality control of intracellular entities in eukaryotes. In the past few years, mounting evidence indicates that microRNAs (miRNAs)-mediated post-transcriptional regulation of gene expression represents an integral part of the autophagy regulatory network and may have a substantial effect on autophagy-related physiological and pathological conditions including cancer. Herein, we examine some of the molecular mechanisms by which miRNAs manipulate the autophagic machinery to maintain cellular homeostasis and their biological outputs during cancer development. A better understanding of interaction between miRNAs and cellular autophagy may ultimately benefit future cancer diagnostic and anticancer therapeutics.","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91213374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-22DOI: 10.14293/S2199-1006.1.SOR-LIFE.AWPDLZ.V1
S. Bashammakh, Salim Seyfried, M. Bader, Katarina Kotnik Halavaty
Serotonin (5-HT) is not only a neurotransmitter but also a mediator of developmental processes in vertebrates. In this study, we analyzed the importance of 5-HT during zebrafish development. The expression patterns of three zebrafish tryptophan hydroxylase isoforms (Tph1A, Tph1B, Tph2), the rate-limiting enzymes in 5-HT synthesis, were analyzed and compared to the appearance and distribution of 5-HT. 5-HT was found in the raphe nuclei correlating with tph2 expression and in the pineal gland correlating with tph1a and tph2 expression. tph2 deficient fish generated with antisense morpholino oligonucleotides exhibited morphogenesis defects during pharyngeal arch development. The correct specification of neural crest cells was not affected in tph2 morphants as shown by the expression of early markers, but the survival and differentiation of pharyngeal arch progenitor cells were impaired. An organizing role of 5-HT in pharyngeal arch morphogenesis was suggested by a highly regular pattern of 5-HT positive cells in this tissue. Moreover, the 5-HT2B receptor was expressed in the pharyngeal arches and its pharmacological inhibition also induced defects in pharyngeal arch morphogenesis. These results support an important role of Tph2-derived serotonin as a morphogenetic factor in the development of neural crest derived tissues.
{"title":"Serotonin is required for pharyngeal arch morphogenesis in zebrafish","authors":"S. Bashammakh, Salim Seyfried, M. Bader, Katarina Kotnik Halavaty","doi":"10.14293/S2199-1006.1.SOR-LIFE.AWPDLZ.V1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-LIFE.AWPDLZ.V1","url":null,"abstract":"Serotonin (5-HT) is not only a neurotransmitter but also a mediator of developmental processes in vertebrates. In this study, we analyzed the importance of 5-HT during zebrafish development. The expression patterns of three zebrafish tryptophan hydroxylase isoforms (Tph1A, Tph1B, Tph2), the rate-limiting enzymes in 5-HT synthesis, were analyzed and compared to the appearance and distribution of 5-HT. 5-HT was found in the raphe nuclei correlating with tph2 expression and in the pineal gland correlating with tph1a and tph2 expression. tph2 deficient fish generated with antisense morpholino oligonucleotides exhibited morphogenesis defects during pharyngeal arch development. The correct specification of neural crest cells was not affected in tph2 morphants as shown by the expression of early markers, but the survival and differentiation of pharyngeal arch progenitor cells were impaired. An organizing role of 5-HT in pharyngeal arch morphogenesis was suggested by a highly regular pattern of 5-HT positive cells in this tissue. Moreover, the 5-HT2B receptor was expressed in the pharyngeal arches and its pharmacological inhibition also induced defects in pharyngeal arch morphogenesis. These results support an important role of Tph2-derived serotonin as a morphogenetic factor in the development of neural crest derived tissues.","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79375458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-19DOI: 10.14293/S2199-1006.1.SOR-PHYS.AVBRMV.V1
A. Buep
Intermolecular associations in liquid systems of non-polar and slightly polar compounds were studied through excess molar volumes (VE M), and excess dielectric properties (e E and n2 E D ) for mixtures of carbon tetrachloride (CCl4) with benzene (C6H6), toluene (C6H5CH3), and p-xylene (p ðCH3Þ2C6H4). These excess properties were calculated from measurements of density (q), static permittivity (e), and refractive index (nD) over the whole range of concentrations, at 298.15 K. The values of the excess dielectric properties for these mixtures were fitted in two different ways, one through least squares using the Redlich–Kister equation and the other using a model developed to explain deviations from ideality. The first fit was found to be descriptive while the second gave the equilibrium constant values for the interaction products actually formed in the mixtures and the respective electronic polarizabilities and dipole moments, indicating the existence of interaction products. INTRODUCTION In previous work we studied the intermolecular associations in liquids through theoretical and experimental studies of the dielectric behavior of binary liquid mixtures [1–4]. In the present work on intermolecular associations in liquids we report measurements of permittivities, refractive indices, and densities for the CCl4 þ C6H6, + C6H5CH3, and + p ðCH3Þ2C6H4 mixtures over the whole range of concentrations at 298.15 K. These mixtures are of considerable interest because in them the departures from ideality stems not only from dispersion, dipolar, and inductive forces, but also from the specific interactions that lead to the formation of chargetransfer complexes between the vacant 3D level of the chlorine atom in CCl4 and the π cloud of the aromatic hydrocarbons [5, 6]. In particular the studies of the static permittivity of solutions, measured with high precision, has the advantage that the experimental values are very sensitive to the existence of different interaction products that may be formed in the mixtures [7]. The experimental values of density (q), static permittivity (e), and refractive index for sodium light (nD) can be used to calculate the molar excess volume (VE M), the excess static permittivity (eE), and the excess permittivity at optical frequency (n2 E D ) over the whole range of concentrations. The excess values for the various mixtures can then be fitted using the Redlich–Kister [8] relation, however this was found to be insufficient, being only descriptive, therefore a model was developed to explain the excess dielectric considering all species present in the mixtures [3]. This previously developed model, based on the additivity of the electrical susceptibilities of the species present in a solution, required the formation of complexes 1:1 in the three systems studied to explain the departures from the ideality. However in the system CCl4 þ C6H6 this did not seemed to be sufficient making it necessary consider the existence of another type
通过四氯化碳(CCl4)与苯(C6H6)、甲苯(C6H5CH3)和对二甲苯(p ðCH3Þ2C6H4)的混合物的超摩尔体积(VE M)和超介电性能(e e和n2 e D)，研究了非极性和微极性化合物在液体体系中的分子间缔合。在298.15 K下，通过测量整个浓度范围内的密度(q)、静态介电常数(e)和折射率(nD)来计算这些多余的特性。用两种不同的方法拟合了这些混合物的多余介电性能值，一种是使用Redlich-Kister方程通过最小二乘法，另一种是使用一个用来解释偏离理想的模型。发现第一个拟合是描述性的，而第二个拟合给出了混合物中实际形成的相互作用产物的平衡常数值以及各自的电子极化率和偶极矩，表明相互作用产物的存在。在之前的工作中，我们通过对二元液体混合物介电行为的理论和实验研究来研究液体中的分子间联系[1-4]。在目前关于液体分子间缔合的工作中，我们报告了在298.15 K的整个浓度范围内CCl4 þ C6H6， + C6H5CH3和+ p ðCH3Þ2C6H4混合物的介电常数，折射率和密度的测量。这些混合物是相当有趣的，因为在它们中，偏离理想状态不仅源于色散、偶极和感应力，而且还源于导致CCl4中氯原子的空三维能级与芳烃π云之间形成电荷转移配合物的特定相互作用[5,6]。特别是对溶液静态介电常数的研究，其测量精度很高，其优点是实验值对混合物中可能形成的不同相互作用产物的存在非常敏感[7]。钠光的密度(q)、静态介电常数(e)和折射率(nD)的实验值可用于计算整个浓度范围内的摩尔多余体积(VE M)、多余静态介电常数(eE)和多余光频介电常数(n2 e D)。然后可以使用Redlich-Kister[8]关系拟合各种混合物的多余值，但是发现这是不够的，只是描述性的，因此开发了一个模型来解释考虑混合物中存在的所有物种的多余介电[3]。这个先前开发的模型，基于溶液中存在的物质的电导率的可加性，需要在研究的三个系统中形成1:1的配合物来解释偏离理想状态。然而，在CCl4 þ C6H6体系中，这似乎是不够的，因此有必要考虑另一种复合体的存在来解释偏离介电理想性。为了绘制理论曲线，可以随机生成混合物中实际形成的相互作用产物的平衡常数值以及各自的电子极化率和偶极矩，以验证用该方法得到的值与由混合焓测量得到的值是否一致。期望通过这种方式可以验证其他相互作用产品的存在。反应级化合物分馏两次，保存在黑暗的瓶子里，在干燥的氮气下。苯、甲苯和对二甲苯在金属钠上回流。气相色谱纯度优于99.9 mol%。在所有馏分中，只有达到报告沸点的中间馏分和约70%的馏分是SOR-PHYS
{"title":"Dielectric properties of liquid systems: study of interactions in the systems carbon tetrachloride with benzene, toluene, and p-xylene","authors":"A. Buep","doi":"10.14293/S2199-1006.1.SOR-PHYS.AVBRMV.V1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-PHYS.AVBRMV.V1","url":null,"abstract":"Intermolecular associations in liquid systems of non-polar and slightly polar compounds were studied through excess molar volumes (VE M), and excess dielectric properties (e E and n2 E D ) for mixtures of carbon tetrachloride (CCl4) with benzene (C6H6), toluene (C6H5CH3), and p-xylene (p ðCH3Þ2C6H4). These excess properties were calculated from measurements of density (q), static permittivity (e), and refractive index (nD) over the whole range of concentrations, at 298.15 K. The values of the excess dielectric properties for these mixtures were fitted in two different ways, one through least squares using the Redlich–Kister equation and the other using a model developed to explain deviations from ideality. The first fit was found to be descriptive while the second gave the equilibrium constant values for the interaction products actually formed in the mixtures and the respective electronic polarizabilities and dipole moments, indicating the existence of interaction products. INTRODUCTION In previous work we studied the intermolecular associations in liquids through theoretical and experimental studies of the dielectric behavior of binary liquid mixtures [1–4]. In the present work on intermolecular associations in liquids we report measurements of permittivities, refractive indices, and densities for the CCl4 þ C6H6, + C6H5CH3, and + p ðCH3Þ2C6H4 mixtures over the whole range of concentrations at 298.15 K. These mixtures are of considerable interest because in them the departures from ideality stems not only from dispersion, dipolar, and inductive forces, but also from the specific interactions that lead to the formation of chargetransfer complexes between the vacant 3D level of the chlorine atom in CCl4 and the π cloud of the aromatic hydrocarbons [5, 6]. In particular the studies of the static permittivity of solutions, measured with high precision, has the advantage that the experimental values are very sensitive to the existence of different interaction products that may be formed in the mixtures [7]. The experimental values of density (q), static permittivity (e), and refractive index for sodium light (nD) can be used to calculate the molar excess volume (VE M), the excess static permittivity (eE), and the excess permittivity at optical frequency (n2 E D ) over the whole range of concentrations. The excess values for the various mixtures can then be fitted using the Redlich–Kister [8] relation, however this was found to be insufficient, being only descriptive, therefore a model was developed to explain the excess dielectric considering all species present in the mixtures [3]. This previously developed model, based on the additivity of the electrical susceptibilities of the species present in a solution, required the formation of complexes 1:1 in the three systems studied to explain the departures from the ideality. However in the system CCl4 þ C6H6 this did not seemed to be sufficient making it necessary consider the existence of another type","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"28 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72371930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-19DOI: 10.14293/S2199-1006.1.SOR-LIFE.AEJRV9.V1
L. Roseti, M. Serra, B. Grigolo
Current European regulations define in vitro expanded cells for clinical purposes as substantially manipulated and include them in the class of Advanced Therapy Medicinal Pro‐ ducts to be manufactured in compliance with current Good Manufacturing Practice. These quality requirements are generally thought to be elaborate and costly. However, they ensure three main product characteristics: safety, consis‐ tency, and absence of cross-contamination. The term crosscontamination is used to indicate misidentification of one cell line or culture by another. The Good Manufacturing Practice Guidelines suggest some recommendations in order to prevent cross-contaminations and require a demonstration that the implemented actions are effective. Here we report some practical examples useful both to minimize crosscontamination risks in an Advanced Therapy Medicinal Products production process and to evaluate the efficacy of the adopted measures.
{"title":"Measures to minimize cross-contamination risks in Advanced Therapy Medicinal Product manufacturing","authors":"L. Roseti, M. Serra, B. Grigolo","doi":"10.14293/S2199-1006.1.SOR-LIFE.AEJRV9.V1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-LIFE.AEJRV9.V1","url":null,"abstract":"Current European regulations define in vitro expanded cells for clinical purposes as substantially manipulated and include them in the class of Advanced Therapy Medicinal Pro‐ ducts to be manufactured in compliance with current Good Manufacturing Practice. These quality requirements are generally thought to be elaborate and costly. However, they ensure three main product characteristics: safety, consis‐ tency, and absence of cross-contamination. The term crosscontamination is used to indicate misidentification of one cell line or culture by another. The Good Manufacturing Practice Guidelines suggest some recommendations in order to prevent cross-contaminations and require a demonstration that the implemented actions are effective. Here we report some practical examples useful both to minimize crosscontamination risks in an Advanced Therapy Medicinal Products production process and to evaluate the efficacy of the adopted measures.","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82981059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-19DOI: 10.14293/S2199-1006.1.SOR-CHEM.AALL9P.V1
Uchechukwu, T. Wirth, S. A. Egu
Palladium-catalyzed Buchwald-Hartwig aminations of various quinolinequinone derivatives give excellent yields of novel 6-arylamino derivatives of the disubstituted quinolinequinones and 3-arylamino derivatives of the corresponding naphthoquinones. The precursor quinolinequinones are prepared in a three-step sequence from 8-hydroxyquinoline. The transition-metal catalyzed arylations of 6,7-dibromo-5,8-quinolinequinone, 6,7-chloro-5,8-quinolinequinone and 2,3-dichloro-1,4-naphthoquinone are reported for the first time and offer fast and easy access to their derivatives.
{"title":"Synthesis of Quinolinequinone Derivatives and related Carbocyclic Compounds","authors":"Uchechukwu, T. Wirth, S. A. Egu","doi":"10.14293/S2199-1006.1.SOR-CHEM.AALL9P.V1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-CHEM.AALL9P.V1","url":null,"abstract":"Palladium-catalyzed Buchwald-Hartwig aminations of various quinolinequinone derivatives give excellent yields of novel 6-arylamino derivatives of the disubstituted quinolinequinones and 3-arylamino derivatives of the corresponding naphthoquinones. The precursor quinolinequinones are prepared in a three-step sequence from 8-hydroxyquinoline. The transition-metal catalyzed arylations of 6,7-dibromo-5,8-quinolinequinone, 6,7-chloro-5,8-quinolinequinone and 2,3-dichloro-1,4-naphthoquinone are reported for the first time and offer fast and easy access to their derivatives.","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78261104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-18DOI: 10.14293/S2199-1006.1.SOR-CHEM.AB3R7E.V1
Jiayu Xin
{"title":"The neighbouring effect of isosorbide and its epimers in their reactions with dimethyl carbonate","authors":"Jiayu Xin","doi":"10.14293/S2199-1006.1.SOR-CHEM.AB3R7E.V1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-CHEM.AB3R7E.V1","url":null,"abstract":"","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73614700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-18DOI: 10.14293/S2199-1006.1.SOR-CHEM.AYZQJS.V1
M. Barberio
{"title":"Active and Stable Platinum/Ionic Liquid/Carbon Nanotube Electrocatalysts for Oxidation of Methanol","authors":"M. Barberio","doi":"10.14293/S2199-1006.1.SOR-CHEM.AYZQJS.V1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-CHEM.AYZQJS.V1","url":null,"abstract":"","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89412862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-18DOI: 10.14293/S2199-1006.1.SOR-CHEM.AD1QVW.V2
N. Shibata
The activation of aromatic diaryl isoxazoles with strong electron-withdrawing groups, such as the nitro, triflyl, and the phenylsulfonyl groups, at the 4-position has enabled the first regioand diastereoselective difluoromethylation at the 5-position of isoxazoles by nucleophilic addition using (difluoromethyl) trimethylsilane, Me3SiCF2H, to provide difluoromethylated isoxazolines in good yields. Conjugated styryl-4-nitroisoxazoles were also nicely converted into the corresponding CF2H adducts with high regioand excellent diastereoselectivities. Since the trifluoromethylated analogs of the corresponding diaryl-isoxazolines are effective ectoparasiticides, represented by fluralaner, should a series of difluoromethylated isoxazolines be obtained, they would be of great importance as promising drug candidates in this field. Heterocycles have an extensive history and are present in a wide variety of drugs, most vitamins, many natural products, biomolecules, and biologically active compounds [1–4]. Manmade fluorinated organic compounds have become a remarkable success in the pharmaceutical industry, despite their relatively young history [5–20]. In this context, fluorinated heterocycles have gained attention as new drug candidates over the past few decades in medicine and agro-chemistry [21–28]. Fluorinated and trifluoromethylated compounds have been well targeted in this research area [5–20, 21–28], and difluoromethylated compounds are next [16, 21–28]. The difluoromethyl (CF2H) group is known to be isosteric and isopolar to a hydroxy (OH) and thiol (SH) unit. The CF2H group can also act as a more lipophilic hydrogen donor than OH and NH groups through hydrogen bonding [31–34]. Thus, the difluoromethylation of biologically active molecules is an effective strategy for the design new candidates of pharmaceuticals and agrochemicals [16]. BRAVECTOTM (fluralaner) is a highly potent insect and acarid RDL and GluCl inhibitor that was just recently approved in chewable tablets for dogs against fleas and ticks [35]. A systematically large number of research disclosed that 3,5-diaryl-5-(trifluoromethyl)-2-isoxazoline unit 1 is a key skeleton for its biological activity [36–38]. Since 2010, our group has also made contributions to this fascinating structure by the direct late-stage trifluoromethylation of aromatic isoxazoles with Ruppert–Prakash reagent (trifluoromethyl) trimethylsilane (Me3SiCF3) [39–40, 41], and a fluorinated building block strategy based on the use of inexpensive reagents under organocatalysis with an eye on industrial purposes [36–38]. We are now interested in the synthesis of difluoromethyl analogs of this key structure, i.e., 3,5-diaryl-5-(difluoromethyl)-2-isoxazolines 2. More than 27,000 isoxazolines 1 with a quaternary carbon bearing a CF3 group at the 5-position have been synthesized and patented [42]; however, common structures bearing a CF2H group 2 are rare [43] (19 compounds, 4 patents Figure 1). In this paper, we disclose the fi
{"title":"Direct Nucleophilic Difluoromethylation of Aromatic Isoxazoles Activated by Electron-Withdrawing Groups Using (Difluoromethyl)trimethylsilane","authors":"N. Shibata","doi":"10.14293/S2199-1006.1.SOR-CHEM.AD1QVW.V2","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-CHEM.AD1QVW.V2","url":null,"abstract":"The activation of aromatic diaryl isoxazoles with strong electron-withdrawing groups, such as the nitro, triflyl, and the phenylsulfonyl groups, at the 4-position has enabled the first regioand diastereoselective difluoromethylation at the 5-position of isoxazoles by nucleophilic addition using (difluoromethyl) trimethylsilane, Me3SiCF2H, to provide difluoromethylated isoxazolines in good yields. Conjugated styryl-4-nitroisoxazoles were also nicely converted into the corresponding CF2H adducts with high regioand excellent diastereoselectivities. Since the trifluoromethylated analogs of the corresponding diaryl-isoxazolines are effective ectoparasiticides, represented by fluralaner, should a series of difluoromethylated isoxazolines be obtained, they would be of great importance as promising drug candidates in this field. Heterocycles have an extensive history and are present in a wide variety of drugs, most vitamins, many natural products, biomolecules, and biologically active compounds [1–4]. Manmade fluorinated organic compounds have become a remarkable success in the pharmaceutical industry, despite their relatively young history [5–20]. In this context, fluorinated heterocycles have gained attention as new drug candidates over the past few decades in medicine and agro-chemistry [21–28]. Fluorinated and trifluoromethylated compounds have been well targeted in this research area [5–20, 21–28], and difluoromethylated compounds are next [16, 21–28]. The difluoromethyl (CF2H) group is known to be isosteric and isopolar to a hydroxy (OH) and thiol (SH) unit. The CF2H group can also act as a more lipophilic hydrogen donor than OH and NH groups through hydrogen bonding [31–34]. Thus, the difluoromethylation of biologically active molecules is an effective strategy for the design new candidates of pharmaceuticals and agrochemicals [16]. BRAVECTOTM (fluralaner) is a highly potent insect and acarid RDL and GluCl inhibitor that was just recently approved in chewable tablets for dogs against fleas and ticks [35]. A systematically large number of research disclosed that 3,5-diaryl-5-(trifluoromethyl)-2-isoxazoline unit 1 is a key skeleton for its biological activity [36–38]. Since 2010, our group has also made contributions to this fascinating structure by the direct late-stage trifluoromethylation of aromatic isoxazoles with Ruppert–Prakash reagent (trifluoromethyl) trimethylsilane (Me3SiCF3) [39–40, 41], and a fluorinated building block strategy based on the use of inexpensive reagents under organocatalysis with an eye on industrial purposes [36–38]. We are now interested in the synthesis of difluoromethyl analogs of this key structure, i.e., 3,5-diaryl-5-(difluoromethyl)-2-isoxazolines 2. More than 27,000 isoxazolines 1 with a quaternary carbon bearing a CF3 group at the 5-position have been synthesized and patented [42]; however, common structures bearing a CF2H group 2 are rare [43] (19 compounds, 4 patents Figure 1). In this paper, we disclose the fi","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76717160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-15DOI: 10.14293/S2199-1006.1.SORCHEM.AYZQJS.V1
E. Sadeghinezhad
{"title":"Active and Stable Platinum/Ionic Liquid/Carbon Nanotube Electrocatalysts for Oxidation of Methanol","authors":"E. Sadeghinezhad","doi":"10.14293/S2199-1006.1.SORCHEM.AYZQJS.V1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SORCHEM.AYZQJS.V1","url":null,"abstract":"","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84697450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2014-12-12DOI: 10.14293/S2199-1006.1.SOR-MED.ATXB4F.V1
Hani M. Annabi, Charles Fleischer, R. Taylor, Steven Gruendling, J. Pergolizzi, A. Bermúdez
{"title":"Carotid Endarterectomy with Local Anesthesia and LMA/General Anesthesia","authors":"Hani M. Annabi, Charles Fleischer, R. Taylor, Steven Gruendling, J. Pergolizzi, A. Bermúdez","doi":"10.14293/S2199-1006.1.SOR-MED.ATXB4F.V1","DOIUrl":"https://doi.org/10.14293/S2199-1006.1.SOR-MED.ATXB4F.V1","url":null,"abstract":"","PeriodicalId":91169,"journal":{"name":"ScienceOpen research","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73689385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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