1,720,995 research outputs found
Synthese funktionalisierter und amphiphiler Poly(aminoester) durch organokatalytische Ringöffnungspolymerisation N-acylierter 1,4-Oxazepan-7-one
Get PDFPoly(aminoester) (PAE) weisen sowohl Ester- als auch Aminogruppen innerhalb ihrer
Wiederholungseinheiten auf. Die spaltbaren Estergruppen machen sie zu einem interessanten abbaubaren Material. Darüber hinaus können über die Aminogruppen unterschiedliche Seitenketten eingebracht werden, um deren Materialeigenschaften und Funktionalität anzupassen. Dies macht sie relevant für biomedizinische Anwendungen wie etwa die Transfektion oder den Wirkstofftransport. Mit dem Anspruch, definierte und segmentierte Polymerstrukturen darzustellen, wurden bisher nur wenige zyklische Monomere genutzt, um funktionelle PAEs über Kettenpolymerisation darzustellen. Darunter fallen N-Acyl-1,4-oxazepan-7-one (OxPs), die im Rahmen dieser Arbeit durch organokatalytische Ringöffnungspolymerisation (ROP) zu amphiphilen und oxidationsresponsiven N-acylierten PAEs umgesetzt werden. Das Einleitungskapitel (Kapitel 1) beginnt mit einer Übersicht über die (Bio-)Abbaubarkeit von Polymermaterialien. Daraufhin wird die bisherige Forschung an PAEs und ihre Darstellung über unterschiedliche Polymerisationsmethoden erläutert. Im weiteren Verlauf wird die organokatalytische Ringöffnungspolymerisation vorgestellt, sowie das Verhalten amphiphiler Moleküle beschrieben. In Kapitel 3 steht die Synthese von N-Acyl-1,4-oxazepan-7-on-Derivaten über zwei unterschiedliche Synthesestrategien im Fokus. Neben Monomeren mit Aryl- und Alkylresten werden auch funktionalisierbare Reste zugänglich gemacht. Die dargestellten Monomere werden zu einer Reihe von N-acylierten Poly(aminoestern) umgesetzt und diese charakterisiert. Sowohl ein hydrophiles als auch ein hydrophobes Polymer mit Alkylseitenkette werden auf ihren Abbau in wässrigem und organischem Lösungsmittel bei unterschiedlichen pH-Werten sowie in der Anwesenheit von Enzymen getestet. Die beiden Monomere zur Darstellung des hydrophilen und hydrophoben Polymers mit Alkylseitenketten werden zu amphiphilen AB-Diblockcopolymeren und ABA-Triblockcopolymeren mit variierenden Molekulargewichtsanteilen der jeweiligen Segmente umgesetzt (Kapitel 4). Der Einfluss der hydrophilen Anteile auf die Wasserlöslichkeit sowie die Selbstassemblierung der Amphiphile zu Aggregaten wird untersucht. Abschließend wird eine Thioetherfunktion in die Polymerseitenkette eines amphiphilen AB-Diblockcopolymers integriert und die Oxidationsresponsivität des Materials analysiert (Kapitel 5). Die in wässriger Umgebung gebildeten Polymeraggregate, deren Löslichkeit sich durch die Oxidation der Seitenketten zu Sulfoxiden verändert, werden abschließend hinsichtlich der oxidationsresponsiven Freigabe von hydrophobem Cargo untersucht.179 Seiten ; Illustrationen, Diagramm
Nitrogen insertion as a strategy for the synthesis of γ-Lactams
No full textIn this thesis, four comprehensive methodologies have been conceived that combine ringexpansion, nitrogen insertion and desymmetrization for the access of achiral and chiral
γ-lactams, a pivotal core scaffold in numerous drug molecules.
In the first work, amino diphenylphosphinates have been identified as suitable amine source
for the ring-expansion of cyclobutanones towards γ-lactams. Through intensive mechanistic
studies, an aza-Baeyer-Villiger rearrangement has been unveiled, showing the tetrahedral
Criegee-type structure as important intermediate. The stereochemical course aligned
with the parent Baeyer-Villiger reaction, demonstrating a regioselective and siteselective
insertion process. Besides that, the synthesized drug molecule Rolipram and its N-substituted derivatives display the remarkable principle of late-stage skeletal editing.
The second work builds upon the achievements of my master’s thesis. Herein, the desymmetrization of prochiral cyclobutanones was described using a chiral amino alcohol, enabling the straightforward synthetic route to chiral N-protected γ-lactams. To conclude this project, an effective deprotection protocol showcased the access of synthetically useful pyrrolidines. In addition to that, the formal synthesis of the drug Pregabalin underscores the importance of this method within the realm of nitrogen insertion processes.
The third work of this research endeavor overcame some of the limitations encountered in
the previous works. A synthetic route for the construction of novel chiral amino phosphinates was developed. These chiral amine sources were successfully incorporated into the aza-Baeyer-Villiger methodology, enabling the direct access of γ-lactams in moderate enantioselectivities. Further investigation into the stability of these chiral aminating reagents unveiled slow racemization rates, partially explaining the observed insufficient stereoinduction. The final work describes a possible alternative for the low stereoinduction by using a catalytic approach. Here, organocatalysts and a chiral N,N’-dioxide-Sc-complex were employed, which showed a catalytic approach in the presence of Sc(OTf)3. However, neither the a chiral N,N’-dioxide-Sc-complex nor organocatalysts could induce the enantioselectivity.XXIV, 168 Seiten ; Illustrationen, Diagramm
Secondary structure mimetic polymer and peptide conjugates : synthesis and structural investigations
Get PDFEs wurde der Einfluss von β-Turn Mimetika auf die Strukturbildung von Polymeren und Peptiden untersucht. Dazu wurden Polymerkonjugate aus helikalen Polyisocyanaten hergestellt und mittels CD Spektroskopie untersucht. Es zeigte sich ein Chiralitätstransfer von der chiralen Turn Struktur auf die Polymerkette, der sowohl vom Abstand zwischen Turn und Polymerkette als auch vom Lösungsmittel abhängig ist. Peptidkonjugate des Peptids Amyloid Beta (Aβ40) wurden durch gezielten Einbau artifizieller β-Turn Mimetika in der Region von Valin-24 bis Lysin-28 synthetisiert. Die modifizierten Peptide zeigten eine deutliche Veränderung des Aggregationsverhaltens und der Fibrillenbildung. In Abhängigkeit von der Turn Struktur konnte die Aggregation beschleunigt, verzögert oder komplett inhibiert werden. Zusätzlich war es möglich die Aggregation von Aβ40 durch Zugabe der Peptidkonjugate zu inhibieren.The influence of β-turn mimetics on the structure formation upon linkage with a polymer or peptide chain was investigated. Polymer conjugates bearing helical polyisocyanates were synthesized and investigations via circular dichroism spectroscopy revealed an induction effect from the chiral turn mimetic onto the polymer chain. This effect showed a dependency on the distance and the solvent used. Peptide conjugates of the amyloid beta peptide (Aβ40) were obtained by introduction of artificial turns in the region of valine-24 to lysine-28. The modifications revealed a strong change of the aggregation behavior and fibril formation. Depending on the turn structure, aggregation was enhanced, delayed or completely inhibited. Furthermore, inhibition of the aggregation of Aβ40 was induced by addition of peptide conjugates
Preparation and exploitation of tailored polymer resins for use in dynamic combinatial library synthesis
No full textThe thermodynamically controlled synthesis, amplification and isolation of macrocydic receptors from dynamic combinatorial libraries (DCLs) has been achieved in a single step using polymer-supported templates. By combining synthesis and affinity chromatography into one single step tedious separations via chromatographic techniques can be avoided, which opens new preparative possibilities especially in more complex libraries comprising an increased number of building blocks.EThOS - Electronic Theses Online ServiceGBUnited Kingdo
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
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
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