1,720,978 research outputs found
Regio‐ and Stereoselective Functionalization Enabled by Bidentate Directing Groups
No full text© 2021 The Chemical Society of Japan & Wiley-VCH GmbHChelation-assisted C−H bond and alkene functionalization using bidentate directing groups offers an elegant and versatile approach to overcome regiocontrol issues by allowing the catalyst to come into close proximity with the targeted sites. In this personal account, we highlight our recent works in developing regio- and stereocontrolled functionalizations through transition-metal catalysis enabled by bidentate directing groups. We classify our results into two categories: (1) regioselective alkene functionalization using bidentate directing groups, and (2) asymmetric C–H functionalization using chiral bidentate directing groups. Furthermore, density functional theory studies to elucidate the origin of the regio- and stereoselectivity exerted by bidentate directing groups are discussed.11Nsciescopu
Two-Track Virtual Screening Approach to Identify the Dual Inhibitors of Wild Type and C481S Mutant of Bruton's Tyrosine Kinase
No full textBruton's tyrosine kinase (BTK) is responsible for the pathogenesis of various autoimmune diseases and chronic lymphocytic leukemia. However, the discovery of efficient medicines has seen limited success due to the constitutively active mutants that acquired the drug resistance. To disclose the dual inhibitors against the wild-type BTK and the problematic drug-resistant C481S mutant, a large chemical library was virtually screened with extensive molecular docking simulations using two target proteins. As a consequence of imposing the configurational restraint to make a hydrogen bond in the hinge region of BTK as well as modifying the ligand dehydration term in the scoring function, a total of 20 dual inhibitors were discovered with the range of the associated IC50 values from 2.5 to 15 mu M. All these dual inhibitors revealed the inhibitory activity against the C481S mutant to a comparable extent to that measured for the wild type. Among the new inhibitors, N-(3,5-dimethoxyphenyl)-6,7-dimethoxyquinazolin-4-amine (1) appeared to be most suitable as a starting point of the lead optimization due to the highest biochemical potency against the C481S mutant as well as the lowest molecular weight. To increase the potential of a drug candidate, 1 was modified into 6,7-dimethoxy-N-(pyridin-3-yl)quinazolin-4-amine (12) via chemical synthesis so as to possess better physicochemical properties without loss of the biochemical potency. 12 is suggested as a new effective molecular core from which numerous druggable dual inhibitors of the wild-type BTK and the C481S mutant would be derivatized.11Nsciescopu
Photoinduced difunctionalization with bifunctional reagents containing N-heteroaryl moieties
No full textBifunctional reagents that serve as dual coupling partners with an activating species have emerged as valuable synthetic tools in organic chemistry. They allow for the development of diverse reaction modes with enhanced efficiency and structural variability, which is in high demand for atom-economic and sustainable synthesis. Among them, bifunctional reagents containing N-heteroaryl groups have received much attention due to their ability to introduce privileged N-heteroaryl moieties into complex molecules that are otherwise challenging to access. Furthermore, these reagents have been employed under visible-light conditions to achieve various synthetic applications, enabling difunctionalization of alkenes, alkynes, and [1.1.1]propellanes under mild reaction conditions, providing access to highly functionalized N-heteroarenes. In this review, we provide an overview of the recent achievements and applications of photoinduced difunctionalization using bifunctional reagents containing N-heteroaryl groups. We systematically categorize the representative contributions in the field based on bifunctional reagents and their reactivity patterns. This review aims to highlight the potential of these reagents as powerful synthetic tools for sustainable and diverse synthesis.11Nsciescopu
Site-Selective Pyridine C-H Alkylation with Alcohols and Thiols via Single-Electron Transfer of Frustrated Lewis Pairs
No full textA unified strategy for the deoxygenative or desulfurative pyridylation of various alcohols and thiols has been developed through a single-electron transfer (SET) process of frustrated Lewis pairs (FLPs) derived from pyridinium salts and PtBu3. Mechanistic studies revealed that N-amidopyridinium salts serve as effective Lewis acids for the formation of FLPs with PtBu3, and the generated phosphine radical cation ionically couples with the in situ generated xanthate, eventually affording the alkyl radical through facile beta-scission under photocatalyst-free conditions. The reaction efficiency was further accelerated by visible-light irradiation. This method is conceptually appealing by using encounter complexes in FLP chemistry to promote SET, which provides a previously unrecognized opportunity for the selective heteroarylation of a diverse range of alcohols and thiols with various functional groups, even in complex settings under mild reaction conditions.11Nsciescopu
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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