1,720,962 research outputs found
Sustainable Synthetic Methodologies for New Antiviral Production
Get PDFThis thesis investigates novel synthetic methods to access antiviral compounds, focusing on three key areas: the development of modified nucleosides, the exploration nucleotide chemistry to access a novel NAADP derivative and the optimization of the industrial scale process for producing an active pharmaceutical ingredient (API). Nucleosides, as essential building blocks of DNA and RNA, are involved in many cellular processes. Their modified counterparts, known as nucleoside analogs, mimic natural nucleosides and are able to interfere with cellular processes, becoming critical in treating various disease including viral infections and cancer. Due to its favourable properties, morpholine was used as a ribose surrogate for the synthesis of a class of modified nucleosides which are called “morpholino nucleosides”. The first objective of this thesis consisted in developing an alternative synthetic route for morpholino nucleosides, a promising class of nucleoside analogs. Using enantiopure glycidol as starting material, a novel pathway was devised to produce optically pure morpholino nucleosides. Central to our strategy is a functionalization step of the key intermediate, morpholine hemiacetal, with natural or modified nucleobases under Lewis acid-promoted glycosylation conditions. Optimization studies led to the identification of TMSOTf as the most effective Lewis acids, which predominantly yielded β-anomers. This study presented an adaptable strategy for morpholino nucleoside synthesis, opening avenues for further investigation into their biological potential.
Research carried out during the six months at the University of Hamburg contributed to a deeper understanding of nucleoside chemistry, focusing on synthesizing a membrane-permeable derivative of nicotinic acid adenine dinucleotide phosphate (NAADP), a key molecule involved in calcium-mediated signaling. The work involved the development of a new method for the independent access, through different strategies, to modified adenosine and stabilized nicotinic acid derivatives. These advances enhance the understanding of nucleotide modifications and their applications in medicinal chemistry, particularly in signal transduction.
Collaboration with OLON S.p.A. was dedicated to the optimization of the large-scale synthesis of an API focusing on three main objectives. To improve efficiency and sustainability, an enantiopure piperidine derivative was used as substrate instead of the racemic mixture, increasing reaction specificity and bypassing the resolution step. Refinements in the challenging nucleophilic aromatic substitution step simplified the processes, reducing waste while enhancing scalability. A combined deprotection and acylation method was developed, achieving the same high yields and purity while minimizing complexity. These innovations align with green chemistry principles, reducing environmental impact and supporting industrial-scale pharmaceutical production.This thesis investigates novel synthetic methods to access antiviral compounds, focusing on three key areas: the development of modified nucleosides, the exploration nucleotide chemistry to access a novel NAADP derivative and the optimization of the industrial scale process for producing an active pharmaceutical ingredient (API). Nucleosides, as essential building blocks of DNA and RNA, are involved in many cellular processes. Their modified counterparts, known as nucleoside analogs, mimic natural nucleosides and are able to interfere with cellular processes, becoming critical in treating various disease including viral infections and cancer. Due to its favourable properties, morpholine was used as a ribose surrogate for the synthesis of a class of modified nucleosides which are called “morpholino nucleosides”. The first objective of this thesis consisted in developing an alternative synthetic route for morpholino nucleosides, a promising class of nucleoside analogs. Using enantiopure glycidol as starting material, a novel pathway was devised to produce optically pure morpholino nucleosides. Central to our strategy is a functionalization step of the key intermediate, morpholine hemiacetal, with natural or modified nucleobases under Lewis acid-promoted glycosylation conditions. Optimization studies led to the identification of TMSOTf as the most effective Lewis acids, which predominantly yielded β-anomers. This study presented an adaptable strategy for morpholino nucleoside synthesis, opening avenues for further investigation into their biological potential.
Research carried out during the six months at the University of Hamburg contributed to a deeper understanding of nucleoside chemistry, focusing on synthesizing a membrane-permeable derivative of nicotinic acid adenine dinucleotide phosphate (NAADP), a key molecule involved in calcium-mediated signaling. The work involved the development of a new method for the independent access, through different strategies, to modified adenosine and stabilized nicotinic acid derivatives. These advances enhance the understanding of nucleotide modifications and their applications in medicinal chemistry, particularly in signal transduction.
Collaboration with OLON S.p.A. was dedicated to the optimization of the large-scale synthesis of an API focusing on three main objectives. To improve efficiency and sustainability, an enantiopure piperidine derivative was used as substrate instead of the racemic mixture, increasing reaction specificity and bypassing the resolution step. Refinements in the challenging nucleophilic aromatic substitution step simplified the processes, reducing waste while enhancing scalability. A combined deprotection and acylation method was developed, achieving the same high yields and purity while minimizing complexity. These innovations align with green chemistry principles, reducing environmental impact and supporting industrial-scale pharmaceutical production
Morpholine Scaffolds’ Preparation for Foldamers’ Design and Construction
Get PDFThis review highlights the advances in the synthesis of morpholine building blocks useful for artificial oligomers synthesis and peptide foldamers or biopolymers. Both morpholino nucleosides and morpholine derived from amino acids have been considered focusing on the preparation of antisense strands, peptides and bio-based materials.This review highlights the advances in the synthesis of morpholine building blocks useful for artificial foldamers synthesis. Both morpholino nucleosides and morpholine derived from amino acids have been considered focusing on the preparation of antisense strands, peptides and bio-based materials
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Cu(OTf)2-catalyzed multicomponent reactions
Get PDFThis review reports the achievements in copper(II) triflate-catalyzed processes concerning the multicomponent reactions, applied to the synthesis of acyclic and cyclic compounds. In particular, for the heteropolycyclic systems mechanistic insights were outlined as well as cycloaddition and aza-Diels–Alder reactions were included. These strategies have gained attention due to their highly atom- and step-economy, one-step multi-bond forming, mild reaction conditions, low cost and easy handling
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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