In recent years, palladium-catalyzed direct arylation of (hetero)aromatics with aryl halides through a CH bond activation has become a popular method for generating carbon-carbon bonds. A wide ...variety of heteroaromatics such as furans, thiophenes, thiazoles, or even pyridines can be employed to prepare arylated heterocycles. Conversely, the formation of biphenyl derivatives through CH bond activation has attracted less attention, owing to the lower reactivity of CH bonds of most benzene derivatives. However, over the last few years several new results using modified and improved catalysts and reaction conditions, especially using polyfluorobenzene derivatives, have been reported permitting the synthesis of fluoro-containing biphenyl derivatives at synthetically useful yields. As fluoro-substituents on benzene rings appear to present a very specific effect, which promote such couplings, we summarize here the various methods allowing the synthesis of fluoro-containing biaryls by metal-catalyzed so called "direct arylation" of (poly)fluorobenzene derivatives. For most of these reactions, aryl halides have been used as the coupling partners, though a several examples employing other coupling partners, such as tosylates or boronic acids, are also known. Moreover, the reaction can be performed with several metal catalysts. This methodology allows the synthesis of complex molecules containing fluorine atoms in only a few steps, and will certainly give the access to a very wide variety of new fluorinated biphenyls useful to both material and biochemists. PUBLICATION ABSTRACT
An orthogonal aminoacyl-tRNA synthetase/tRNA pair is a crucial prerequisite for site-specific incorporation of unnatural amino acids. Due to its high codon suppression efficiency and full ...orthogonality, the pyrrolysyl-tRNA synthetase/pyrrolysyl-tRNA pair is currently the ideal system for genetic code expansion in both eukaryotes and prokaryotes. There is a pressing need to discover or engineer other fully orthogonal translation systems. Here, through rational chimera design by transplanting the key orthogonal components from the pyrrolysine system, we create multiple chimeric tRNA synthetase/chimeric tRNA pairs, including chimera histidine, phenylalanine, and alanine systems. We further show that these engineered chimeric systems are orthogonal and highly efficient with comparable flexibility to the pyrrolysine system. Besides, the chimera phenylalanine system can incorporate a group of phenylalanine, tyrosine, and tryptophan analogues efficiently in both E. coli and mammalian cells. These aromatic amino acids analogous exhibit unique properties and characteristics, including fluorescence, post-translation modification.
I estimate that a margin as trading frictions has an effect on the strategies of writing options. The important results are as follows.First, by the margin requirement is increased, the size of short ...position is reduced. Second, the discrimination of a margin requirement is due to the way that the member margin is imposed less about 1/3 than the customer margin by derivatives market business regulation in KRX. Third, the customer margin is from 1.4 to 1.6 times more than the member margin, and the margin “haircut” ratio is similar to that of the margin. Fourth, by target weight increases, the difference between target weight and effective weight is increased. Fifth, by target weight is increased, the member have higher returns on writing combination position than the customer have. It means that when investors increase the size of short position using all of account, they not only can suffer loss because of margin call but also can make profit.Overall, the difference between the returns of the member and the returns of the customer can be quite substantial. So, this paper contributes to the literature that studies the impact of the different imposition of margins by showing how frictions limit the customer from supplying liquidity to the market and hence releasing pressure on the member.
We assessed the in vitro antiviral activity of remdesivir and its parent nucleoside GS-441524, molnupiravir and its parent nucleoside EIDD-1931 and the viral protease inhibitor nirmatrelvir against ...the ancestral SARS-CoV2 strain and the five variants of concern including Omicron. VeroE6-GFP cells were pre-treated overnight with serial dilutions of the compounds before infection. The GFP signal was determined by high-content imaging on day 4 post-infection. All molecules have equipotent antiviral activity against the ancestral virus and the VOCs Alpha, Beta, Gamma, Delta and Omicron. These findings are in line with the observation that the target proteins of these antivirals (respectively the viral RNA dependent RNA polymerase and the viral main protease Mpro) are highly conserved.
•The omicron SARS-CoV-2 variant remains susceptible for GS-441524, Remdesivir, EIDD-1931, Molnupiravir and Nirmatrelvir.•The target genes of these antivirals are highly conserved between SARS-CoV-2 variants.•Similarly, the alpha, beta, gamma and delta variants remain susceptible to these antivirals.
Abstract Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available ...antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M2 protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin remains the backbone treatment for chronic hepatitis C; the addition of serine protease inhibitors improves the treatment outcome of patients infected with hepatitis C virus genotype 1. Chronic hepatitis B can be treated with interferon or a combination of nucleos(t)ide analogues. Notably, almost all the nucleos(t) ide analogues for the treatment of chronic hepatitis B possess anti-human immunodeficiency virus properties, and they inhibit replication of hepatitis B virus by serving as competitive substrates for its DNA polymerase. Some antiviral drugs possess multiple potential clinical applications, such as ribavirin for the treatment of chronic hepatitis C and respiratory syncytial virus and cidofovir for the treatment of cytomegalovirus and other DNA viruses. Drug resistance is an emerging threat to the clinical utility of antiviral drugs. The major mechanisms for drug resistance are mutations in the viral DNA polymerase gene or in genes that encode for the viral kinases required for the activation of certain drugs such as acyclovir and ganciclovir. Widespread antiviral resistance has limited the clinical utility of M2 inhibitors for the prevention and treatment of influenza infections. This article provides an overview of clinically available antiviral drugs for the primary care physician, with a special focus on pharmacology, clinical uses, and adverse effects.
Ten 3-methylflavone derivatives were studied. Previously reported NMR data of some derivatives were corrected and/or completed, including the complete assignment of the two known natural derivatives. ...The complete super(1)H and super(13)C NMR assignments were achieved by combination of one-dimensional and two-dimensional NMR experiments. Copyright copyright 2013 John Wiley & Sons, Ltd. Ten 3-methylflavone derivatives were studied. Previously reported NMR data of some derivatives were corrected and/or completed, including the complete assignment of the two known natural derivatives. The complete super(1)H and super(13)C NMR assignments were achieved by combination of one-dimensional and two-dimensional NMR experiments.
The complete super(1)H and super(13)C assignments of eight bioactive indeno1,2-bindole-10-one derivatives were accomplished by the combined use of one-dimensional and two-dimensional NMR experiments. ...Copyright copy 2013 John Wiley & Sons, Ltd. Complete super(1)H and super(13)C assignments of eight bioactive indeno1,2-bindole-10-one derivatives were accomplished by the combined use of one-dimensional and two-dimensional NMR experiments.
The synthesis, structure elucidation and the complete super(1)H and super(13)C signal assignment of a series of dioxolane derivatives of 20-hydroxyecdysone, synthesized as novel modulators of ...multidrug resistance, are presented. The structures and NMR signal assignment were established by comprehensive one-dimensional and two-dimensional NMR spectroscopy supported by mass spectrometry. Copyright copy 2013 John Wiley & Sons, Ltd. The synthesis, structure elucidation and the complete super(1)H and super(13)C signal assignment of a series of dioxolane derivatives of 20-hydroxyecdysone, synthesized as novel modulators of multidrug resistance, are presented. The structures and NMR signal assignment were established by comprehensive one-dimensional and two-dimensional NMR spectroscopy supported by mass spectrometry.
Recently, due to its passive property, the smart beta has become one of the most interest topics in searching the alpha. In this paper, we attempt to show whether the smart beta strategy generate ...abnormal excess return, in tradition, which are known as the exclusive property of active fund. Further, we attempt to verify the key drivers of the alpha in the smart beta portfolios. For this purpose, we categorize various smart beta strategies by their scheme for asset picking and risk reduction. Then, based on our categorization, we evaluate and analyze the performance of smart beta strategy in perspective. Our empirical analyses show following results: applying alternative risk reduction scheme to traditional market index portfolio would results in enhanced efficiency; however, without combining any asset picking scheme, the performance of the smart beta portfolio seems explained by the Fama-French 3 factor. Our results lead us to conjecture that it is not the portfolio weighting scheme alone but in association with asset selection scheme that generate significant alpha in the smart beta strategy. In actual practice, our results imply that any passive fund may succeed in seeking the alpha without active strategy, thereby avoiding the risk of market timing and saving the management cost.
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