To see the other types of publications on this topic, follow the link: Chemoselective Synthesis.
Dissertations / Theses on the topic 'Chemoselective Synthesis'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 43 dissertations / theses for your research on the topic 'Chemoselective Synthesis.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Kasper, Marc-André. "Chemoselective synthesis of functional drug conjugates." Doctoral thesis, Humboldt-Universität zu Berlin, 2020. http://dx.doi.org/10.18452/20870.
Full textAbstract:
In der vorliegenden Arbeit wird eine modulare Reaktionssequenz von zwei aufeinanderfolgenden chemoselektiven Umwandlungen vorgestellt: Es wird gezeigt, dass Vinyl- und Ethynylphosphonamidate chemoselektiv mit Cysteinen von Proteinen und Antikörpern reagieren. Weiterhin wird gezeigt, dass elektrophile Phosphonamidate durch eine vorhergehende chemoselektive Staudinger-Phosphonit Reaktion zwischen Aziden und ungesättigten Phosphoniten in das gewünschte Molekül eingebaut werden können. Hierbei wird ein elektronenreiches Phosphonit in ein elektronenarmes Phosphonamidat umgewandelt, welches somit für die nachfolgende Thiol-Addition aktiviert wird. Die beschriebene Methode erweitert das bestehende Repertoire von Biokonjugationen durch die Einführung eines neuen Konzepts: Eine chemoleselektive Reaktion, die Reaktivität für eine nachfolgende Biokonjugation induziert. Da Phosphonamidat-Konjugationen an Cysteine herausragende Eigenschaften, wie hohe Selektivität für Cysteine, saubere Reaktionsprodukte und eine hervorragende Stabilität mitbringen, wird im zweiten Teil beschrieben wie Phosphonamidate für die Anbindung von zytotoxischen Wirkstoffen an tumor-bindende Antikörper genutzt werden können um Antikörper-Wirkstoff-Konjugate (ADCs) herzustellen. Ein einfaches Syntheseprotokoll für die Herstellung, ausgehend von einem nicht gentechnisch veränderten Antikörper mit nur geringen Überschüssen des Wirkstoffs wird vorgestellt. Phosphonamidat-verbundene ADCs zeigen im direkten Vergleichen zum zugelassenen, Maleimid-verbundenen Adcetris überlegende Eigenschaften, wie eine erhöhte Stabilität in Serum und eine erhöhte in vivo Wirksamkeit in einem Tumor Mausmodel. Zusammenfassend verbindet die hier vorgestellte Methode einen einfachen synthetischen Zugang mit hoher Selektivität, überragender Konjugat-Stabilität und der Möglichkeit hochwirksame Wirkstoffkonjugate herzustellen und wird daher aller Voraussicht nach einen großen Beitrag zum Gebiet der zielgerichteten Therapie leisten.The present work introduces a modular reaction sequence of two chemoselective manipulations in a row. It is shown that vinyl- and ethynylphosphonamidates react selectively with cysteine residues on proteins and antibodies. Most importantly, those electrophilic phosphonamidates can be incorporated into a given molecule in another preceding chemoselective Staudinger-phosphonite reaction (SPhR) from unsaturated phosphonites and azides. During this reaction, an electron-rich phosphonite is transformed into an electron-deficient phosphonamidate that is thereby activated for the subsequent thiol addition. The described technique thereby extends the existing repertoire of bioconjugations by introducing a new concept in protein synthesis: A chemoselective reaction that induces reactivity for a subsequent bioconjugation. Since phosphonamidate conjugations to cysteine hold outstanding features such as high selectivity for cysteine, clean reaction products and excellent stability of the protein adducts in biological environments, it is described in the second part of the present work how ethynylphosphonamidates can be employed for the conjunction of tumor-sensing antibodies and cytotoxic drugs to generate Antibody-Drug-Conjugates (ADCs). A simple synthetic protocol starting from unengineered antibodies, using only a slight excess of the desired drug in a one-pot synthesis protocol is introduced. In a direct comparison to the maleimide containing FDA-approved Adcetris, phosphonamidate linked ADCs show a superior behaviour in terms of linkage stability in serum, combined with an increased in vivo efficacy in a tumor xenograft mouse model. Taken together, the method described herein combines simple synthetic access with high selectivity, superior conjugate stability and the possibility to synthesize highly efficacious drug conjugates and is therefore likely to have a great contribution to the field of targeted therapeutics.
2
Li, Ronald Chuan-Teh. "Synthesis of polymer scaffolds for bioconjugation via chemoselective reactions." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1781842041&sid=3&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full text
3
李安怡 and On-yi Lee. "Synthesis of heterocycles via phenylseleno group transfer radical cyclization and chemoselective reductive amination promoted by InCl3." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B3955756X.
Full text
4
Steffensen, Mackay Bagley. "Methods for the syntheses of compositionally diverse dendrimers." Texas A&M University, 2004. http://hdl.handle.net/1969.1/2724.
Full textAbstract:
Dendrimers are a unique class of macromolecules that present perfect branching on a molecular scale. The pattern of branching at the atomic scale is compared to the branching of trees, from whence dendrimers get their name. Dendrimers have been attractive synthetic targets for the past twenty years. The methods and building blocks used in the synthesis of dendrimers vary, but molecules of this class of polymeric materials all possess symmetrical branching emanating from the core. At each branch point the number of groups increases exponentially. Efforts directed toward the synthesis of dendrimers presenting multiple functional groups at the surface and within the dendrimer structure are described.
Methods are described which provide access to dendrimers in a one-pot per generation fashion, with triazines as the common moiety. Chemoselective routes utilize the temperature dependant substitution of cyanuric chloride to construct dendrimers, obviating the use of protected monomers or the need to manipulate functional groups during the synthesis. These methods are atom economical, as the only by-products are HCl and a base to scavenge it. The methods are efficient, with typical isolated yields of product in the middle to high ninety percent range, often on a multi-gram scale. Methods are described for conducting three separate reactions in a single pot. Specific emphasis is placed on structural control of the interior and surface groups of the dendrimers.
The synthesis of a G3 dendrimer of layered composition is described. The use of a different difunctional linkage group for each generation of dendrimer growth produced a G3 dendrimer with layered composition without the use of protecting groups or functional group interconversions.
A G3 dendrimer was synthesized presenting five different functionalities at the periphery on a 10 gram scale, resulting in approximately 70% overall yield. The peripheral groups are composed of orthogonal functionality, which can be independently and selectively unmasked or manipulated in the presence of the other functionality.
The syntheses of dendrimers incorporating the short linker hydrazine produce materials with interesting physical properties as well as a low ratio of carbon to nitrogen. The use of dendrimers in the construction of novel macromolecular constructs is also described.
5
Nischan, Nicole [Verfasser]. "Chemoselective Synthesis of Functional Peptide- and Protein-Conjugates for Intracellular Applications / Nicole Nischan." Berlin : Freie Universität Berlin, 2015. http://d-nb.info/1070820040/34.
Full text
6
Imayoshi, Ayumi. "Discrimination of Mobile Supramolecular Chirality: Acylative Molecular Transformation by Organocatalysis." 京都大学 (Kyoto University), 2016. http://hdl.handle.net/2433/215486.
Full text
7
He, Lu-Ying [Verfasser]. "Chemoselective Cross-Coupling Reactions as Tools in Synthesis and Applications for Polymer Chemistry / Lu-Ying He." Kiel : Universitätsbibliothek Kiel, 2015. http://d-nb.info/1070819247/34.
Full text
8
Lee, On-yi. "Synthesis of heterocycles via phenylseleno group transfer radical cyclization and chemoselective reductive amination promoted by InCl3." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/HKUTO/record/B3955756X.
Full text
9
Hahn, Gabriela [Verfasser], and Rhett [Akademischer Betreuer] Kempe. "Reusable Ni-Catalysts for the Highly Chemoselective Synthesis of Primary Amines / Gabriela Hahn ; Betreuer: Rhett Kempe." Bayreuth : Universität Bayreuth, 2019. http://d-nb.info/1189207222/34.
Full text
10
Kasper, Marc-André [Verfasser], Christian [Gutachter] Hackenberger, Dorothea [Gutachter] Fiedler, and Jeffrey W. [Gutachter] Bode. "Chemoselective synthesis of functional drug conjugates / Marc-André Kasper ; Gutachter: Christian Hackenberger, Dorothea Fiedler, Jeffrey W. Bode." Berlin : Humboldt-Universität zu Berlin, 2020. http://d-nb.info/1203126840/34.
Full text
11
Siebertz, Kristina D. "Application of chemoselective tools for the protein semi-synthesis of tau and the development of a novel photo-cleavable tag." Doctoral thesis, Humboldt-Universität zu Berlin, 2019. http://dx.doi.org/10.18452/19827.
Full textAbstract:
Posttranslationale Modifikationen sind chemische Veränderungen, die ein Protein nach der Translation durchläuft. Sie sind wichtig für die Regulierung der Funktion, Struktur und Interaktion von Proteinen. Die Einführung von Modifikationen in Biomoleküle ist zudem ein Hilfsmittel in der Chemischen Biologie, um neue Informationen über ihr Verhalten zu erlangen und ihre Aktivität zu verändern.
Die Fehlregulierung von posttranslationalen Modifikationen steht häufig in direkter Verbindung zum Ausbruch von Krankheiten. Ein Beispiel ist das Tau Protein welches eine Schlüsselrolle in der Alzheimer Erkrankung hat. Im Laufe der Krankheit wird Tau hyperphosphoryliert, was zu einem Funktionsverlust des Proteins und zur Bildung von nicht-löslichen Aggregaten führt. Die Mechanismen hinter dieser Fehlregulierung zu eluieren gehört zu einer der großen Herausforderungen der Alzheimerforschung. Diese Doktorarbeit hat sich mit der Entwicklung einer neuen semi-synthetischen Ligationsstrategie beschäftigt, die es ermöglichen soll die Rolle einzelner Phosphorylierungen in der Prolin-reichen Region des Tau Proteins zu untersuchen. Hierfür wurden geeignete Ligationsstellen identifiziert, Ligationsmöglichkeiten geprüft und die Synthese der einzelnen Fragmente optimiert.
Desweiteren wurde in dieser Dissertation eine neuartige Anwendung der Staudinger-Phosphonit Ligation entwickelt, die es ermöglicht mit Boran-geschützten P(III) Verbindungen azidhaltige Moleküle zu lichtspaltbaren Phosphonamidaten zu modifizieren. Die P(III) Bausteine beinhalteten dabei nicht nur zwei lichtspaltbare 2-Nitrobenzyl-Substituenten, sondern erlauben zudem über eine Alkingruppe eine vielfältige Funktionalisierung. Die Bestrahlung durch UV Licht induziert die Spaltung der P-N Bindung der Phosphonamidate und setzte das Ursprungsmolekül mit einer zusätzlichen Aminfunktion frei. Dahingehend wurden erste Schritte unternommen, damit die Lichtspaltung keine Modifikation mehr am Ursprungsmolekül hinterlässt.Post-translational modifications are essential in the regulation of the function, folding and interaction of proteins. Similarly, the modification of biomolecules is a main tool in chemical biology to gain new insights into their molecular mechanisms and to alter and fine-tune their activity. The dysregulation of post-translational modifications is often associated with disease. An example are the abnormally hyperphosphorylated tau proteins that are the main component of neurofibrillary tangles, one of the pathological hallmarks of the neurodegenerative disease Alzheimer‘s disease. The origin of these hyperphosphorylations, which render a soluble and mostly unstructured protein into insoluble aggregates, is a key question in Alzheimer research. First steps towards a tau semi-synthesis that allow for the site-specific introduction of phosphorylations in the proline-rich domain were taken by identifying suitable ligation sites, finding the ideal sequential ligation strategy, providing reliable protein expression protocols and optimizing the synthesis of the synthetic peptides equipped with phosphorylated residues. Furthermore, this thesis explored the use of the Staudinger-phosphonite reaction in the synthesis of photo-cleavable phosphonamidates to modify biomolecules in a reversible manner. This conjugation method allowed for the chemoselective modification of an azido-containing target molecule with a borane-protected P(III) reagent that was equipped with photo-cleavable 2-nitrobenzyl substituents and one alkyne for functionalization. UV irradiation induced the phosphonamidate P-N bond cleavage and resulted in the release of the target molecule with an additional amine functionality. In this regard, first steps were undertaken to develop a traceless variant of this cleavage. The application of the photo-cleavable phosphonamidates was demonstrated in streptavidin-mediated immobilization assays, which is just one example for the use of this valuable methodology.
12
Mohammed, Azzam. "Diastereo- and chemoselective oxidative monocyclisations of trienes : application of permanganate mediated oxidative cyclisation to the synthesis of eurylene." Thesis, University of Southampton, 2015. https://eprints.soton.ac.uk/384993/.
Full textAbstract:
A formal synthesis of eurylene (1.1) has been achieved where both trans- and cis-THF fragments were synthesised using diastereo- and chemoselective oxidative monocyclisations of triene systems. Synthesis of the trans-THF aldehyde fragment 1.50 of eurylene was accomplished starting from nerol, using (+)-trans tritylcyclohexanol (TTC) as a chiral auxiliary to direct the stereosfacial selectivity during the oxidative cyclisation of 1,5,9-triene 1.185 by sodium permanganate. The oxidative cyclisation used the new chiral auxiliary (TTC) as a highly effective chiral controller for the formation of the 2,5-substituted THF diol product with high diastereoselectivity (dr ∼13:1). Synthesis of cis-THF right hand fragment 1.189 was also achieved using permanganate mediated oxidative cyclisation of a 1,5,9-triene 1.60. The diastereoselectivity of the oxidation was controlled by using (2S)-10,2 camphorsultam as a chiral auxiliary. Consequently, seven, out of eight, stereogenic centres of eurylene were established by stereoselective permanganate oxidative cyclisations of 1,5,9-trienes. Towards the completion of the total synthesis of eurylene a chiral sulfoxide strategy was investigated to establish the eighth stereogenic centre and couple the two fragments. In addition a hydroxylsulfone dianion coupling strategy was also investigated. The stereochemical correlation for oxidative cyclisation products from trans-cumylcyclohexanol (TCC) and trans-tritylcyclohexanol (TTC) diene and triene esters was achieved. The oxidative cyclisation products were converted to a common intermediate and analysed by chiral HPLC to confirm absolute configuration. NOESY and NOE NMR studies were applied to some of 2 substituted cyclohexyl dienoates and an oxidative cyclisation product to study their conformation in solution.
13
Mosrin, Marc [Verfasser], and Paul [Akademischer Betreuer] Knochel. "Regio- and chemoselective metalations of N-heterocycles : applications to the synthesis of biologically active compounds / Marc Mosrin ; Betreuer: Paul Knochel." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2019. http://d-nb.info/118479412X/34.
Full text
14
Claron, Michaël. "Synthèse de vecteurs peptidiques non-viraux : vectorisation et ciblage tumoral." Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENV036/document.
Full textAbstract:
Dans l’optique de développer de nouveaux agents bio-inspirés pour la détection et/ou le traitement des cellules cancéreuses, nos travaux se sont tournés vers la synthèse de macromolécules peptidiques complexes ayant la capacité de reconnaître les cellules tumorales. Ces travaux visent à développer des molécules permettant de cibler des particularités cellulaires présentes sur les cellules tumorales dans le but d’obtenir un traitement personnalisé via une vectorisation active permettant une augmentation de l'efficacité thérapeutique et une réduction intrinsèque de la toxicité du traitement. Pour cela, ces biomolécules doivent posséder à la fois un site de reconnaissance pour la liaison avec des protéines présentes à la surface de la cellule cible et un ou plusieurs éléments utilisés pour détecter et/ou détruire la cible. Ces systèmes ont été élaborés à partir d'un châssis moléculaire cyclodécapeptidique présentant des propriétés conformationnelles particulières. Plusieurs approches ont été envisagées. La première a consisté à rechercher de nouveaux ligands de récepteurs tumoraux en s'inspirant du domaine de reconnaissance d'un anticorps monoclonal thérapeutique. Dans ce contexte, nous avons proposé la conception de mimes du Rituximab ciblant l'antigène CD20 utilisé dans le traitement des lymphomes Non-Hodgkinien. Dans la seconde approche, nous avons développé des vecteurs destinés à des applications d'imagerie tumorale. Pour cela, des châssis multivalents présentant des ligands peptidiques RGD ciblant l'intégrine alpha-v-beta-3 ont été conjugués avec différents agents de détection puis évalués par des techniques d'imagerie telles que la TEP, la TEMP et l’imagerie optique. Toujours dans un but de diagnostic des cellules tumorales, nous nous sommes par la suite tournés vers l’application à la capture cellulaire. Pour cela, une surface d’or à été modifiée via la formation d’une monocouche organisée SAM (« Self-assembled monolayer ») présentant des cyclodextrines. Un gabarit peptidique adéquat a ainsi permis la capture et le relargage sélectif de cellules tumorales mesurées par la technique de microbalance à quartz. Ces mêmes vecteurs, validés pour le diagnostic ont par la suite été couplés à des peptides cytotoxiques issus d’une protéine pro-apoptotique « Bax ». Enfin, une dernière partie a été consacrée à la recherche de nouveaux composés comportant plusieurs éléments de ciblage tumoraux. Ces molécules présentent deux ligands de ciblage des récepteurs surexprimés sur la membrane et peuvent ainsi permettre une meilleure sélectivité vis-à-vis des tissus tumorauxIn order to develop new agents for cancer diagnosis and treatment, our work aims to synthesize complex peptide macromolecules that are able to specifically recognize cancer cells. Our goal is to increase the therapeutic efficiency and reduce the toxicity of currently available drugs using "targeted strategies". In this context, we designed sophisticated macromolecules encompassing a cell recognition domain and one or several components used to detect and/or destroy the target. This system was prepared starting from a cyclodecapeptidic scaffold presenting particular conformational properties. Different approaches were considered. First of all our work was to investigate new tumor receptor ligands based on the recognition domain of a therapeutics monoclonal antibody. We proposed the design of Rituximab mimics which targets the CD20 antigen used for the treatment of Non-Hodgkin lymphoma. In a second approach, we prepared new vectors for tumor imaging. For this purpose, multivalent scaffolds containing RGD peptide that targets alpha-v-beta-3 integrin were combined with several detection elements and evaluated by using PET, SPECT and optical imaging techniques. We also used this peptide vector for the selective cell capture and release from flowing suspensions, using a gold surface modified with a cyclodextrin-containing self-assembled monolayer (SAM). A scaffold containing ferrocenyl and -RGD- ligands permitted the selective capture and release of tumor cells. This experiment was monitored by QCM-D. This vector has been next grafted to a cytotoxic peptide that was discovered from a pro-apoptotic protein named “Bax”. Finally, we designed new molecules which include an additional ligand for the cell’s surface to increase the selectivity and the affinity of tumor tissue
15
Delost, Michael D. "Synthesis of Amine Derivatives from a “One-Pot” Synthesis of Biphenyl-4-methylazide." Youngstown State University / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1442407733.
Full text
16
Xiao, Ye. "Synthesis and self-assembly of polysaccharide-b-elastin-like polypeptide bioconjugates." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0172.
Full textAbstract:
L’association de polysaccharides naturels et de polypeptides recombinants de type élastine (ELP) dans des structures de copolymères à blocs doit permettre d’accéder à des matériaux possédant des propriétés d’auto-assemblage sous l’action de stimuli et potentiellement bioactifs. Nous avons réalisé et présentons ici la synthèse d'une série de bioconjugués polysaccharide-b-ELP, dans lesquels 4 polysaccharides hydrophiles différents ont été couplés à l'extrémité N-terminale de l’ELP par "chimie click".Ces bioconjugués ont été caractérisés par RMN 1D et 2D, SEC et FTIR. Leur thermo-sensibilité et leur auto-assemblage induit par la température ont été étudiés par spectroscopie UV-Visible, DLS, SLS, SANS et AFM liquide à température contrôlée. Cette étude a démontré que les bioconjugués polysaccharide-b-ELP peuvent s'auto-assembler en milieu aqueux en nanoparticules bien définies au-dessus d'une température de transition spécifique et modulable (Tt) et se désassembler de façon réversible sous la Tt, ce qui les rend particulièrement prometteurs pour la conception de vecteurs de principes actifs à libération contrôlée. La fonctionnalisation chimiosélective des résidus méthionine du segment ELP par chimie de l'oxaziridine a également été exploitée pour moduler les propriétés des bioconjuguésThe combination of natural polysaccharides and recombinant elastin-like polypeptides (ELPs) into block copolymers is expected to lead to materials with precise stimuli-responsive self-assembly properties and bioactivities. Herein, we report the synthesis of a series of polysaccharide-b-ELP bioconjugates, in which 4 different hydrophilic polysaccharides were coupled to the N-terminal end of an ELP via “click chemistry”. The resulting bioconjugates were characterized by 1D and 2D NMR, SEC and FTIR. Their thermal sensitivity and temperature-triggered self-assembly in aqueous solution were investigated by UV-Vis spectrometry, DLS, SLS, SANS and temperature-controlled liquid AFM. This study demonstrated that polysaccharide-b-ELP bioconjugates can self-assemble into well-defined nanoparticles in aqueous condition above a specific and tunable transition temperature (Tt) and reversibly disassemble below the Tt, which make them particularly promising candidates for the design of controlled drug delivery nanocarriers. Chemoselective functionalizations of the ELP segment at methionine residues using oxaziridine chemistry were additionally applied for further tuning of bioconjugates’ properties
17
Ren, Hongjun. "Preparation of Condensed N-Heterocycles via Chemoselective Benzylic C-H Activations and Preparation of Alkenylmagnesium Reagents, Allylic Zinc Reagents and their Applications in Organic Synthesis." Diss., lmu, 2006. http://nbn-resolving.de/urn:nbn:de:bvb:19-62454.
Full text
18
Council, Claire E. "Evaluation of sequential chemoselective peptide ligation and molecular dynamics simulations as tools for the total synthesis of proteins: an example using bovine pancreatic ribonuclease A." Thesis, University of Surrey, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.583341.
Full textAbstract:
Chemoselective ligation between two peptides can be used to produce synthetic peptides and proteins that cannot easily be synthesised as single peptides by solid phase peptide synthesis. Chemoselective reaction between an aldehyde and hydrazine or hydroxylamine, masking the aldehyde as a 1, 2-amino alcohol, has been investigated as a method of sequential ligation that will allow synthesis of individual peptides in high yield and purity, enabling more than two peptides to be ligated. Protected amino acids were used as precursors for the synthesis of 1, 2-amino alcohol derivatives that could be used in solid phase peptide synthesis for the production of peptides bearing a C-terminal 1, 2-amino alcohol, as a masked aldehyde for use in ligation reactions. Limitations of this method led to alternative investigations, using peptides bearing an N-terminal serine as a masked aldehyde, and a C-terminal hydrazide. Bovine pancreatic ribonuclease A was chosen as an example protein for sequential ligation and using this method, peptides were synthesised in high yield and purity for use in ligation reactions. Trial ligation reactions with short test peptides were performed successfully, however problems were experienced during ligations using peptide fragments of ribunuclease due to involvement of the cysteine side chains. Methods to overcome these unwanted reactions resulted in insoluble peptide fragments. Computer modelling using molecular dynamics simulations has been used to investigate the effect of replacing native peptide bonds in ribonuclease on the structure of the protein. The method of molecular dynamics simulation was validated through comparison of the structure of a mutant of ribonuclease from experimental NMR data to the structure produced after a molecular dynamics simulation. Results of the modelling simulations suggest that replacement of native peptide bonds with the chemoselective bond formed through reaction of an aldehyde and hydrazine will have only minor implications for the structure of ribonuclease, and therefore should only have a small impact on enzyme activity .
19
Jiang, Jintao. "Studies Toward Yaku'amide A and Synthesis and Applications of Bulky α,β-Dehydroamino Acids." BYU ScholarsArchive, 2016. https://scholarsarchive.byu.edu/etd/6460.
Full textAbstract:
Yaku'amide A shows a unique inhibitory profile against a series of 39 human cancer cell lines (JFCR39). In our efforts to synthesize yaku'amide A, we have optimized our regioselective base-free aminohydroxylation method with a series of nitrogen sources, developed a chiral reagent-mediated aminohydroxylation strategy and chemoselective deprotections of the resulting aminohydroxylation product, and explored a stereospecific E2 dehydration and O-N acyl transfer sequence. In addition, we have prepared the right-hand tetrapeptide and the NTA subunit. For our bulky α,β-dehydroamino acids project, we have developed strategies to incorporate α,β-dehydroamino acids such as ΔVal and ΔEnv into small synthetic peptides via Solid Phase Peptide Synthesis (SPPS). We have also prepared two analogues of a monomeric helical peptide with 13 residues.
20
Siebertz, Kristina D. [Verfasser], Christian P. R. [Gutachter] Hackenberger, Hans [Gutachter] Börner, and Dirk [Gutachter] Schwarzer. "Application of chemoselective tools for the protein semi-synthesis of tau and the development of a novel photo-cleavable tag / Kristina D. Siebertz ; Gutachter: Christian P. R. Hackenberger, Hans Börner, Dirk Schwarzer." Berlin : Humboldt-Universität zu Berlin, 2019. http://d-nb.info/1189071436/34.
Full text
21
Siebertz, Kristina [Verfasser], Christian P. R. [Gutachter] Hackenberger, Hans [Gutachter] Börner, and Dirk [Gutachter] Schwarzer. "Application of chemoselective tools for the protein semi-synthesis of tau and the development of a novel photo-cleavable tag / Kristina D. Siebertz ; Gutachter: Christian P. R. Hackenberger, Hans Börner, Dirk Schwarzer." Berlin : Humboldt-Universität zu Berlin, 2019. http://d-nb.info/1189071436/34.
Full text
22
Gavel, Marine. "Nouveaux développements chimiques pour la conception d'inhibiteurs de glycosyltransférases Carbene-mediated quaternarization of the anomeric position of carbohydrates: synthesis of allylic ketopyranosides, access to the missing α-gluco and β-manno stereoisomers, and preparation of quaternary 2-deoxy 2-acetamido sugars Regio- and chemoselective deprotection of primary acetates by zirconium hydrides." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMIR09.
Full textAbstract:
Ces travaux de thèse ont été consacrés au développement de voies de synthèses permettant l'obtention de structures cétopyranosidiques modulables en vue du développement d'outils chimiques dédiés à la glycobiologie. Nous avons tout d'abord travaillé au déploiement de séquences réactionnelles ouvrant l'accès à des glycophosphomimétiques possédant une unité triméthylène phosphonate. Par ailleurs, nous avons mis au point une nouvelle méthode de déprotection régiosélective de la position primaire de sucres peracétylés utilisant un mélange bimétallique de zirconium et d'aluminium permettant de faciliter l'accès à des (oligo)saccharides ayant des liens glycosidiques α-1,6. Enfin, en combinant ces développements chimiques, nous avons souhaité préparer des inhibiteurs potentiels de glycosyltransférases bi-substrats possédant à la fois un mime du groupe partant du donneur de glycosyle et de l'accepteur connectés à la position anomère quaternaire des cétopyranosidesThe goal of this project is to challenge the hypothesis that a non-natural sugar with a quaternary anomeric position might be the central core of a powerful and selective inhibitor of glycosyltransferase. Our design is relying on a key quaternary anomeric centre that provide the unique opportunity to incorporate in a single innovative structure the acceptor, the donor and the leaving group released during the formation of the glycosidic linkage. The functionnalization of the ketopyranosides that will be at the centre of this new class of potent glycosyltransferases inhibitors rely on original synthetic methods allowing introduction of a trimethylene phosphonate and regioselective deprotection of primary position of acetylated sugars for building alpha-1,6 glycosidic linkages
23
Jiménez-Castells, Carmen 1982. "Capture and identification of carbohydrate-binding proteins by SPR and CREDEX-MS." Doctoral thesis, Universitat Pompeu Fabra, 2010. http://hdl.handle.net/10803/7237.
Full textAbstract:
Carbohydrate-binding proteins of non-immunological origin -lectins- have been recognized over the last decades as decisive players in numerous biological processes, ranging from cellcell communication, fertilization, pathogen-cell adhesion to metastasis. Consequently, there is an increasing interest in finding powerful and nanosized tools to screen for these molecules and to study their carbohydrate interactions in detail. Here, two complementary approaches are described to characterize lectin-carbohydrate interactions with high sensitivity, low sample consumption, and without the need for sample labelling: SPR and CREDEX-MS. In SPR, we have developed an approach where the sugar is immobilized onto a sensor surface through a tailor-made peptide module that allows (1) to capture the lectin, (2) to characterize the interaction through kinetic and thermodynamic parameters, and (3) to identify the interacted protein by mass spectrometry. In CREDEX-MS, based on proteolytic excision of proteincarbohydrate complexes and mass spectrometric analysis, the peptides comforming the carbohydrate binding domain are identified.Las lectinas (proteínas de origen no inmune capaces de reconocer azúcares) se han revelado en las últimas décadas como participantes cruciales en multitud de procesos biológicos, tales como la comunicación célula-célula, la fertilización, la adhesión del patógeno a la célula y la metástasis, entre muchos otros. Por lo tanto, existe un gran interés en el desarrollo de técnicas analíticas potentes para el estudio de las interacciones lectina-carbohidrato. En este trabajo, se describen dos aproximaciones complementarias mediante las cuales se pueden caracterizar las interacciones lectinas-azúcar con gran sensibilidad, poca utilización de muestra y sin la necesitad de ningún marcaje. En la técnica basada en resonancia de plasmón superficial (SPR), el azúcar es inmovilizado sobre una superficie a través de un módulo peptídico, lo cual permite (1) capturar la lectina, (2) caracterizar su interacción mediante parámetros cinéticos y termodinámicos y (3) identificar posteriormente la proteína mediante espectrometría de masas. Complementariamente, la técnica CREDEX-MS, basada en la excisión proteolítica del complejo proteína-azúcar y posterior análisis por espectrometría de masas, nos permite identificar los péptidos que forman parte del dominio de unión al azúcar.
24
Tan, X., H. Zhao, Y. Pan, Na (Anna) Wu, H. Wang, and Z. Chen. "Atom-economical chemoselective synthesis of furocoumarins via cascade palladium catalyzed oxidative aloxylation of 4-oxohydrocoumarins and alkenes." 2014. http://hdl.handle.net/10454/17849.
Full textAbstract:
NoA novel and efficient procedure for the synthesis of furo[3,2-c] coumarins from readily available 4-oxohydrocoumarins and alkenes in the presence of a catalytic amount of Pd(CF3COO)2 has been developed. Atom-economical characteristics and mild conditions of this method are in accord with the concept of modern green chemistry.
25
Tardiff, Bennett Joseph. "PALLADIUM-CATALYZED AMINE SYNTHESIS: CHEMOSELECTIVITY AND REACTIVITY UNDER AQUEOUS CONDITIONS." 2012. http://hdl.handle.net/10222/14784.
Full textAbstract:
The palladium-mediated cross-coupling of aryl electrophiles and amines
(Buchwald-Hartwig amination) has become a widely used method of constructing
arylamine frameworks. A crucial aspect of the advancement of this chemistry has been
the design of ancillary ligands that are able to promote enhanced reactivity in challenging
amination reactions. Despite significant ligand development within the field, challenges
in this chemistry remain.
Chemoselective aminations, wherein one amine substrate undergoes preferential
arylation in the presence of multiple reactive amines has remained an underexplored area
of Buchwald-Hartwig amination chemistry. This thesis describes the use of
[Pd(cinnamyl)Cl]2 and N-[2-di(1-adamantylphosphino)phenyl]morpholine (Mor-
DalPhos) in an extensive study of chemoselective Buchwald-Hartwig aminations, with 62
examples of structurally diverse di-, tri-, and tetraamines obtained in synthetically useful
yields at reasonable catalyst loadings (1-5 mol % Pd). The coordination chemistry of
[(Mor-DalPhos)Pd] species was also explored, as were complementary chemoselective
aminations with the isomeric p-Mor-DalPhos ligand, leading to divergent product formation in some instances. The same [Pd(cinnamyl)Cl]2/Mor-DalPhos catalyst system
used in the chemoselectivity study was also employed in a series of Buchwald-Hartwig
aminations conducted under aqueous and solvent-free conditions, another underexplored
area of this chemistry. A total of 52 amine products were isolated using these
methodologies, moderate catalyst loadings (3 mol % Pd), and without the use of any additional additives, co-solvents, or rigorous exclusion of air.
The synthesis of low-coordinate palladium complexes featuring both NHC and
dialkylchlorophosphine ligands is also discussed herein. These complexes are prepared via a previously unreported and straightforward methodology involving an unusual net PCl bond reductive elimination, and represent a potential new class of pre-catalysts forpalladium-mediated reactions.
26
Guo, Jhe-Ruei, and 郭哲睿. "Studies on the Total Synthesis of Neuritogenic Active Ganglioside SJG-1 by Chemoselective Glycosylation Strategy." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/12445700780636565829.
Full textAbstract:
碩士中原大學
化學研究所
100
The nature product SJG-1 showed the nerve-growth activity, which wad isolatedfrom the sea cucumber S. japonicus. Owing to the biological activity, prompted us to study the total synthesis of these compound. The purpose of this thesis is its chemoselective glycosylation reaction to the rapid synthesis of the target and to shorten the synthetic steps. Up the rapid synthesis of the purpose of this thesis, reference Demchenko strategy for the synthesis of sialic acid glycosides of Neu-4, the introduction of PhS-leaving group; the building unit Glc-6 in the glucose-STaz leaving group. Sugar donor sialic acid Neu-4 with the sugar receptor glucose Glc-6 by glycosylation reaction yield of 62% mixture of disaccharide NG-1, it’s a : b of 3.0: 1.0. disaccharide NG-1 and ceramide amine derivatives Lyx-8 works the glycosylation reaction, get the NGL-1, yield 40%. NGL-1 through a few steps of the reaction, can be successfully synthesized the target SJG-1.
27
周書綺. "Investigation of Chemoselective Intramolecular Wittig Reaction and Its Application in the Synthesis of Benzofurans and Furans." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/89062398914613147560.
Full textAbstract:
碩士國立臺灣師範大學
化學系
100
The investigation of chemoselectivity of reactions always attracts chemists attention because of their importance in the synthesis of complex structures of molecules like natural products. The Wittig reaction is one of the most efficient reactions for carbon-carbon double formation and is widely used in organic synthesis. However,literature survey reveals that for the study of chemoselectivity for known reactions or reagents, few of them are mentioned about intramolecular Wittig reactions. For our interest in chemoselective intramolecular Wittig reactions, we therefore proposed the intermediates 72’ with two possibly reacting ester functions and a phosphorus ylide moiety, which can be prepared from the corresponding Michael acceptors, Et3N, Bu3P, and acid chlorides. The phosphorus ylides 75’ with two possibly reactive functionalties such as an ester and an amide will also be investigated. Our study showed that the preparation of highly functional benzofurans 73, furans 73’ and 76’, indoles 76, and tetrahydrobenzofurans 78 via chemoselective intramolecular Wittig reactions from the corresponding phosphorus ylides 72’ and 75’ can be realized.
28
Wen, Kuo-Shan, and 温國山. "Chemoselective synthesis, antiproliferative activities andSAR study of 1H-pyrazol-5-yl-N,N-dimethylformamidines and pyrazolyl-2-azadienes." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/80295522664933598378.
Full textAbstract:
碩士中國醫藥大學
藥物化學研究所碩士班
100
Chemoselective microwave-assisted amidination was successfully developed to alternatively synthesize 1H-pyrazol-5-yl-N,N-dimethyl-formamidine and pyrazolyl-2-azadiene two classes compounds. All of the starting materials and resulting products were tested against NCI-H226, NPC-TW01, and Jurkat cancer cell lines to evaluate their difference in antiproliferative activities for realizing the structure activity relationship study. Following the SAR result, 1H-pyrazol-5-yl-N,N-dimethylformamidine compounds 2b, 2c and 2d possessed the best potent with IC50 values in low micromolar range. On the other hand, we found that the formyl group at C-4 position and the grafted amidinyl group in the main core of pyrazolic molecule were necessary for the inhibitory activity
29
Mosrin, Marc [Verfasser]. "Regio- and chemoselective metalations of N-heterocycles : applications to the synthesis of biologically active compounds / von Marc Mosrin." 2009. http://d-nb.info/995523398/34.
Full text
30
Wang and 王建益. "Chemoselective synthesis of substituted benzofurans and furo[3,2-c]coumarins from functional phosphorus zwitterions via intramolecular Wittig reactions." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/5q3v84.
Full textAbstract:
碩士國立臺灣師範大學
化學系
103
The thesis is divided into two parts： In the first part, chemoselective synthesis of substituted benzofurans and furo[3,2-c]coumarins from functional phosphorus zwitterions via intramolecular Wittig reactions is described. Based on our previous studies, a phosphine-triggered intramolecular Wittig reaction with high efficiency via phosphorus zwitterions as key intermediates has been developed. The studies included chemoselectivities of acylations and intramolecular Wittig reactions. By employing different addition sequence of the acyl chloride and phosphine reagent, the corresponding furo[3,2-c]coumarin derivative can be synthesized chemoselectively, which has not be reported, to the best of our knowledge. In the second part, enantioselective synthesis of pyran[4,3-b]chromene derivatives via organocatalyzed [3+2] cycloaddition has been investigated. Cinchona alkaloid derived organocatalysts as bases have been exclusively examined for asymmetric [3+2] cycloaddition of o-hydroxy aromatic aldimine and coumarins. In addition, the desired products can be further transformed into complex tricyclic products.
31
Hsiao, Ming-Yu, and 蕭明玉. "Synthesis of 1,3-Benzoxazines via π-insertion reactions of Arynes and N-Acyl imines and Chemoselective Intramolecular Wittig Reactions for the Synthesis of Oxazoles and Benzofurans." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/ubfus5.
Full text
32
"Part I, chemoselective and oxo-controlled s-oxidation of sulfides containing pyridine rings and olefinic double bonds: Part II, directed synthesis of all-Homocalix(n)arenes with various cavity sizes." 1999. http://library.cuhk.edu.hk/record=b5889991.
Full textAbstract:
Ho-Fai Lee.Thesis (M.Phil.)--Chinese University of Hong Kong, 1999.
Includes bibliographical references (leaves 90-91).
Abstracts in English and Chinese.
Acknowledgements --- p.i
Abbreviations --- p.ii
Abstract --- p.iii
Chapter Part I. --- Chemoselective and Oxo-Controlled S-Oxidation of Sulfides Containing Pyridine Rings and Olefinic Double Bonds
Chapter 1.1. --- Introduction --- p.2
Chapter 1.2. --- Results and Discussion --- p.5
Chapter 1.3. --- Conclusion --- p.14
Chapter 1.4. --- Experimental --- p.15
Chapter 1.5. --- References --- p.32
Chapter Part II. --- Directed Synthesis of all-Homocalix[n]arenes with Various Cavity Sizes
Chapter II. 1. --- Introduction --- p.35
Chapter II.2. --- Previous Synthetic Routes for all-Homocalixarenes --- p.37
Chapter II.3. --- Synthetic Plan --- p.39
Chapter II.4. --- Results and Discussion --- p.41
Chapter II.5. --- Conclusion --- p.55
Chapter II.6. --- Experimental --- p.56
Chapter II.7. --- References --- p.90
Chapter Appendix --- 1H and 13C NMR Spectra
List of and 13C NMR Spectra of Part I --- p.92
1Hand 13C NMR Spectra of Part I --- p.93
List of 1H and 13C NMR Spectra of Part II --- p.100
1H and 13C NMR Spectra of Part II --- p.102
33
Lai, Kuan-Yu, and 賴冠妤. "(1) Palladium-catalyzed synthesis of indenobenzofuran from 2-(2-bromobenzoyl)benzofurans(2) Pd-catalyzed the chemoselective synthesis of 4-aryl-4H-chromenes from 2H-chromenes and aryl iodide." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/13883605516297789187.
Full textAbstract:
碩士高雄醫學大學
醫藥暨應用化學研究所
100
Chapter I The key intermediate 2-(2-bromobenzoyl)benzofurans, prepared from salicylaldehydes and 2-bromo-1-(2-bromophenyl)ethanone, were subjected to an intramolecular cyclization catalyzed by Pd(II) to undergo the Heck reaction to yield 6H-indeno[2,1-b]benzofuran-6-ones in moderate to good yields. Meanwhile their congener indenoneaphthofuran also was prepared. Chapter II A new and chemoslective preparation of 4-aryl-4H-chromenes from 3-cyano-2H-chromenes and aryl iodide catalyzed by Pd was described. The key intermidiates, 3-cyano-2H-chromenes prepared from salicylaldehydes with acrylonitrile via the Baylis-Hillman reaction, were respectively reacted with aryl iodide and catalyzed by Pd(II) to undergo the Heck reaction to yield a series of new substituted 4-aryl-4H-chromens.
34
Chang, Tzu-Hsiu, and 張慈修. "Recyclable triethylamine and phosphine: Synthesis of highly functionalized furans via chemoselective reduction/Wittig reactionand Synthesis of 1,3-Benzoxazines via π-insertion reactions of Arynes and N-Acyl imines." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/88477626902562504742.
Full textAbstract:
碩士國立臺灣師範大學
化學系
104
An efficient protocol for the synthesis of highly functionalized furans via intramolecular Wittig reaction has been developed using catalytic amounts of phosphine and triethylamine in the presence of silyl chloride, which served as the promoter to activate the phosphine oxide. Reduction of the activated phosphine oxide by hydrosilane resulted in the generation of phosphine, while the decomposition of conjugate acid of Et3N resulted in the regeneration of base, both of which mediated the formation of phosphorus ylide. Key word : trimethylamine, phosphine, Wittig reaction, functionalized furans. Because arynes are highly reactive species and can undergo a variety of transformations, their chemistry attract chemist a lot of attention. We have successfully utilized the eletron-deficient N-acyl imines to trap the in-situ generated intermediates, benzyne, to obtain the corresponding benzoxazine derivatives in moderate yield. These unprecedented reactions are assumed to be via an unexpected [2+2] cycloaddition of N-acyl imine and benzyne as the key step. Key word : Arynes, N-Acyl imines.
35
Gheorghe, Alexandru [Verfasser]. "Development of new methods for the synthesis of pharmacologically active compounds : synthesis of new immobilized homo- and heterogeneous catalysts for the chemoselective oxidation of alcohols / vorgelegt von Alexandru Gheorghe." 2008. http://d-nb.info/987515152/34.
Full text
36
Moulins, Jonathan. "Synthesis of Heterocycles via Chemoselective Geminal Acylation of 2-Methoxyoxazolidines, E/Z Isomerization in the Metathesis of Allyl Alcohol Derivatives with a First-Generation Ruthenium Catalyst, and Interception of Nazarov Reaction Intermediates of Allenyl Vinyl Ketones with Arenes." 2013. http://hdl.handle.net/10222/37454.
Full textAbstract:
Heterocycles were prepared through the geminal acylation of 2-methoxyoxazolidines with 1,2-bis(trimethylsilyloxy)cyclobutene. It was found that when water was excluded from the standard reaction conditions, regioselectivity of the ring expansion step was reversed, resulting in preferential rupturing of the endocyclic C-O bond instead of the C-N bond. Further cyclization resulted in the generation of 6,5-fused ring systems. The aqueous procedure was found to be applicable to 1,2-bis(trimethylsilyloxy)cyclopentene, resulting in the analogous 6,6-fused ring systems, while the anhydrous procedure failed to promote ring expansion. Tricyclic 6,5,6-fused ring systems were obtained with meso-7,8-bis(trimethylsilyloxy)bicyclo[4.2.0]oct-7-ene using the anhydrous procedure, while the intermediate generated under aqueous conditions failed to undergo ring closing. Allylic alcohol derivatives were subjected to homodimerization in the presence of a first-generation ruthenium catalyst. Previous work suggested that thermodynamic equilibration to the E-isomer was not a significant process for first-generation catalysts. However, product E/Z ratios were, in general, observed to increase significantly over time. In addition, an atmosphere of ethylene promoted reversion to the terminal olefins, leading to rapid E/Z equilibration, albeit at the expense of yield. Brief exposure to ethylene over the course of reaction resulted in a high E/Z ratio in a moderate yield. A 6,6,5-fused ring system was synthesized via the tandem Nazarov cyclization-intramolecular Friedel-Crafts alkylation of the corresponding allenyl vinyl ketone. The presence of electron donating substituents on the arene, as well as a two-carbon tether linking the arene to the allenyl vinyl ketone, were crucial to the success of the reaction. The intermolecular trapping of an allenyl vinyl ketone with substituted arenes was also investigated. Trapping occurred primarily at the electronically preferred position a, while sterically encumbered substrates tended to trap preferentially at the less hindered position c. Surprisingly, 1,3,5-trisubstituted arenes trapped almost exclusively at position a, having overcome significant steric crowding, demonstrated by hindered rotation about the newly formed carbon-carbon bond.
37
Piller, Fabian Michel [Verfasser]. "LiCl-mediated direct insertion of magnesium into aryl, heteroaryl and benzylic halides : regio- and chemoselective synthesis of 5-membered ring heterocycles / Fabian Michel Piller." 2010. http://d-nb.info/1002176751/34.
Full text
38
Ren, Hongjun [Verfasser]. "Preparation of condensed N-heterocycles via chemoselective benzylic C-H activations and preparation of alkenylmagnesium reagents, allylic zinc reagents and their applications in organic synthesis / von Hongjun Ren." 2006. http://d-nb.info/982560370/34.
Full text
39
Barbe, Guillaume. "Synthèse totale de la lépadine B : plate-forme pour la découverte de nouvelles tranformations chimiques." Thèse, 2009. http://hdl.handle.net/1866/3239.
Full textAbstract:
Dans ce document, serons détaillées les résultats de mes travaux de recherche d’études doctorales. Tout d’abord, nous discuterons de la synthèse totale de la lépadine B, la plus courte à paraître dans la littérature à ce jour. Cette synthèse, en plus de valoriser la synthèse asymétrique de pipéridines poly-substituées développée par l’équipe du professeur Charette, mettra à profit une utilisation originale d’une séquence de fermeture-ouverture de cycle par la réaction de métathèse d’alcènes. De plus, nous détaillerons une brève étude mécanistique de cette dernière nous ayant permis la proposition d’un mécanisme peu commun de ce type de séquence réactionnel et dont les conséquences expérimentales sont impressionnantes.
Au cours de cette synthèse, nous avons identifié un synthon d’une grande valeur synthétique. En effet, ne comportant pas moins que quatre centres chiraux, ce synthon pouvait être obtenu énantiopure en seulement trois étapes à partir de la pyridine. Ainsi, nous avons effectué une analyse structurale de ce synthon et avons envisagé une valorisation supplémentaire par une utilisation originale de la fragmentation de Grob. Dans ce contexte, nous avons développé une toute nouvelle synthèse de pipéridines 2,3,6-trisubstituées hautement régio- et diastéréosélective.
Afin de pouvoir réaliser la précédente méthodologie, nous avons dû étudier la réduction d’une amide en présence de groupements fonctionnels sensibles dans les conditions usuelles. Heureusement, l’année précédente nous avions développée une réaction hautement chimiosélective d’amides tertaires. Cette nouvelle réaction, qui a été fondamentalement inspiré par une méthodologie du professeur Charette sur l’activation d’amides, a permis la réduction d’amides tertiaires en présence de fonctions telles les cétone, ester, nitrile, époxyde, insaturations, etc.
Enfin, l’ensemble des connaissances acquises au cours de ces projets a permis l’élaboration d’une toute nouvelle stratégie de synthèse pour la préparation d’indolizidines et quinolizidines. Plus spécifiquement, nous avons développé la première séquence d’activation intramoléculaire et déaromatization asymétrique de la pyridine. Ceci permet d’avoir un accès aux squelettes indolizidine et quinolizidine avec des stéréosélectivités élevées, la nature insaturée de ces derniers laissant également place à une grande flexibilité synthétique. Dans ce contexte, nous allons détailler une très courte synthèse de trans-indolizidines.In this document, the results of Ph.D. thesis will be detailed. First, we will discuss the synthesis of alkaloid lepadin B, the shortest to appear in the literature to date. This synthesis, in addition to validating the asymmetric synthesis of polysubstituted piperidines developed earlier by the group of Professor Charette, will highlight an original use of a ring-closing ring-opening alkene metathesis sequence. Also, a brief mechanistic study of the latter reaction will be detailed, a study which led us to propose an unusual mechanism for this reaction sequence and for which the experimental concequences are impressive. During the total synthesis of lepadin B, we identified a synthon of great synthetic value. Indeed, containing not less than four chiral centres, that synthon could be obtained enantiopure through a short three-step synthesis from pyridine. We performed a structural analysis of this synthon and we envisaged an additional validating through an original use of the Grob fragmentation. Consequently, we developed a new highly regio- and diastereoselective synthesis of 2,3,6-trisubstituted piperidines. To succesfully realize the latter methodology, it was required to perform an amide reduction in the presence of sensitive functionnalities under usual reduction conditions. Fortunatly, we had recently developed a set of conditions for the highly chemoselective reduction of tertiary amides. This new reaction, fundamentaly inspired by an amide activation methodology from Charette’s group, allowed the reduction of amides in the presence of functionalities such as ketone, ester, nitrile, epoxide, unsaturations, etc. Finaly, the knowledge acquired by conducting this research allowed for the elaboration of a new methodology for the synthesis of indolizidines and quinolizidines. Specifically, we developed the first intramolecular pyridine activation-asymmetric dearomatization reaction of the pyridine. This led us to the highly stereoselective access to indolizidine and quinolizidine backbone, the unsaturated nature of which permitting a good degree of synthetic flexibility. In that context, we will detail a short synthesis of trans-indolizidines.
40
Hsu, Wei-Shan, and 許維珊. "(1)Conversion of 3-(chloromethyl)coumarins into alkyl 2H-chromene-3-carboxylates by alkoxides(2)Pd-catalyzed the chemoselective synthesis of alkyl 4-aryl-4H-chromene-3-carboxylates from alkyl 2H-chromene-3-carboxylates and aryl iodides." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/89965633658370624971.
Full textAbstract:
碩士高雄醫學大學
醫藥暨應用化學研究所
101
Chapter 1 A new preparation of alkyl 2H-chromene-3-carboxylates derivatives from the conversion of 3-(chloroalkyl) coumarins with sodium alkoxides was described. 3-(Chloroalkyl) coumarins were prepared from salicylaldehyde and tert-butyl acrylate via the Baylis Hillman reaction , and followed by treated with hydrogen chloride and acetic acid . Chapter 2 A new and chemoslective preparation of 4-aryl-3-carboxylate-4H- chromenes from alkyl 2H-chromene-3-carboxylates and aryl iodide catalyzed by Pd to undergo the Heck reaction was described.
41
Yuan, Tsu-Chun, and 袁子鈞. "（1）Improved and Scalable Synthesis of Bicyclic 1,2,3-Triazolium Ionic Liquids [R-4C-tr][NTf2]（2）Crowned Ionic Liquids and Their Applications to Affinity Extraction of Peptides/Proteins（3）Affinity Ionic Liquids Tailored for Chemoselective Extraction of Copper (II) Ions." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/43119097508886490725.
Full textAbstract:
碩士國立中正大學
化學暨生物化學研究所
104
The first research project—” Improved and Scalable Synthesis of Bicyclic 1,2,3-Triazolium Ionic Liquids [R-4C-tr][NTf2]”—developed novel synthetic routes to bicyclic triazolium ionic liquids. These synthetic routes successfully constructed bicyclic triazoles by taking advantage of an iodosobenzene diacetate-mediated oxidative cyclization as well as the Pd/C catalytic hydrogenation. Our preparation of bicyclic triazoles can be conveniently scalable and proceeds under mild experimental conditions. The second research project—”Crowned Ionic Liquids and Their Applications to Affinity Extraction of Peptides/Proteins”—designed and synthesized a series of crowned ionic liquids containing different sizes of crown ethers. Based on specific recognition of crown ethers to organoammonium ions, these crowned ionic liquids chemoselectively extract lysine or arginine containing peptides and lysine-rich proteins. The third research project—”Affinity Ionic Liquids Tailored for Chemoselective Extraction of Copper(II) Ions”—designed and synthesized affinity ionic liquids and used for chemoselective extraction of copper(II) ions from aqueous solution. The mode of binding interaction of affinity ionic liquid with the copper(II) ion was proposed by comparing with interactions with analogous ionic liquids. Chemoselectivity of copper(II) extraction by affinity ionic liquid was achieved relative to that of other divalent transition-metal cations such as cobalt(II) and nickel(II).
42
Rokade, Balaji Vasantrao. "Copper-Catalyzed Novel Oxidative Transformations : Construction of Carbon-Hetero Bonds." Thesis, 2014. http://etd.iisc.ernet.in/2005/3479.
Full textAbstract:
The thesis entitled “Copper-Catalyzed Novel Oxidative Transformations: Construction of Carbon-Hetero Bonds” is divided into two main sections. Section A deals with the utility of azide as a nitrogen source for C-N bond formation, which is further divided into 4 chapters, and section B presents decarboxylative radical coupling reaction for C-heteroatom bond formation which is further divided in to two chapters.
Section A
Chapter 1 describes an approach for the direct synthesis of nitrile from the corresponding alcohols using azide as a nitrogen source. Nitrile functionality is a versatile and ubiquitous which occurs in a variety of natural products. Nitrile functionality can be easily transformed into a variety of functional groups and products such as aldehydes, ketones, acids, amines, amides and nitrogen-containing heterocycles, such as tetrazoles and oxazoles. In this chapter a successful attempt for developing a novel methodology to oxidize benzylic and cinnamyl alcohols to their corresponding nitriles in excellent yields has been described. This strategy uses DDQ as an oxidant and TMSN3 as a source of nitrogen in the presence of a catalytic amount of Cu(ClO4)2·6H2O. A few representative examples are highlighted in Scheme 1.1
Scheme 1. Oxidative conversion of alcohols to nitriles
Second chapter represents a protocol for the synthesis of 1,5-disubstituted tetrazoles from the corresponding secondary alcohols. Among heterocyles, tetrazole and its derivatives are important class of nitrogen containing molecules. Due to their well-known biological activities as well as vast applications in pharmaceuticals and material science, they are potential targets for synthetic organic chemists. Therefore, a simple and user-friendly method for the synthesis of tetrazole is desirable. In this chapter, a mild and convenient method to synthesize 1,5-disubstituted tetrazoles using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 2).2
Scheme 2. Oxidative conversion of secondary alcohols to tetrazoles
Third chapter presents a method for synthesizing amides from their corresponding secondary alcohols. Amide functionality is a crucial backbone in peptide chemistry, it also serve as an important precursor or intermediate for variety of organic transformations. In this contention, a mild and convenient method to synthesize amides using easily accessible secondary alcohols by employing TMSN3 as a nitrogen source is developed. This reaction is performed in the presence of a catalytic amount of Cu(ClO4)2·6H2O using DDQ as an oxidant under ambient conditions (Scheme 3).3
Scheme 3. Oxidative conversion of secondary alcohols to amides
Additionally, the application of this methodology has also been revealed for the synthesis azides directly from their alcohols. Some of the representative examples are shown in the Scheme 4.3
Scheme 4. Direct conversion of alcohols to their azides.
Fourth chapter describes highly chemoselective Schmidt reaction. The classical Schmidt reaction involves the formation of new carbon-nitrogen bonds in a reaction of a carbon-centred electrophile with hydrazoic acid followed by loss of nitrogen, which usually occurs via a rearrangement. It is well known that under the Schmidt reaction conditions, ketones and carboxylic acids are converted into their corresponding amides and amines respectively, whereas aldehydes furnish a mixture of formanilides and nitriles. In this chapter, Schmidt reaction of aldehydes to obtain their nitriles without formation of the corresponding formanilide is presented (Scheme 5).4 It was also observed that aromatic ketones and acids functionalities were intact under the reaction condition, unlike the conventional Schmidt reaction.
Scheme 5. Highly chemoselective Schmidt reaction
Section B
It is divided into two chapters, describes a copper catalyzed decarboxylative radical coupling for the synthesis of vinyl sulfones and nitroolefins (Scheme 6).
Scheme 6. General strategy for the second part
First chapter narrates a strategy for synthesizing nitroolefins from the α,β-unsaturated carboxylic acids. Nitroolefins represent a unique class of nitro compounds, which have multifaceted utility in organic synthesis. They possess antibacterial, rodent-repelling, and antitumor activities. They serve as important intermediates in organic synthesis. Nitroolefins also react with a variety of nucleophiles, and their electron-deficient character renders them as a powerful dienophiles in Diels-Alder reactions. In our attempt to use the decarboxylative strategy, this chapter describes a method for the nitrodecarboxylation of substituted cinnamic acid derivatives to their corresponding nitroolefins. This nitrodecarboxylation reaction is performed using catalytic amount of CuCl in the presence of air using TBN as a nitrating source (Scheme 7).5 Besides, the reaction provides a useful method for the synthesis of β,β-disubstituted nitroolefin derivatives which are generally difficult to access from other conventional methods. Scheme 7. Decarboxylative nitration
Second chapter presents a new protocol for the synthesis of vinyl sulfones from the α,β-unsaturated carboxylic acid. Vinyl sulfones are versatile building blocks, which find their utility as Michael acceptors and used in cycloaddition reactions. This functional group has also been shown to potently inhibit a variety of enzymatic processes, and thus provides unique properties for drug design and medicinal chemistry. Vinyl sulfones are prominent in medicinal chemistry owing to their wide presence in pharmaceutically active molecules, such as enzyme inhibitors and biological activity. In this chapter, we report a method for the construction of C-S bonds via ligand promoted decarboxylative radical sulfonylation of ,-unsaturated carboxylic acids to synthesize vinyl sulfones using Cu catalysis (Scheme 8).6 This is the first report for this particular conversion.
Scheme 8. Decarboxylative sulfonation
43
McFarlin, Rae. "Chemoselective Functionalization of Carboxylic Acid and Phenol Containing Natural Products and the Development and Use of a Nucleophile Catalyzed Michael Aldol Lactonization Process." Thesis, 2013. http://hdl.handle.net/1969.1/149474.
Full textAbstract:
The development of methods for site-selective derivatization of natural products to enable simultaneous arming and structure activity relationship (SAR) studies has shown great potential for the synthesis of pharmaceutical drug leads and cellular probes for mechanism of action studies. Herein, we describe a strategy to functionalize carboxylic acid and phenol containing natural products. This methodology relies on the in situ generation of diazoalkanes to form the corresponding carbonyl esters and phenolic ethers derived from natural products. We applied this process to several natural products, to begin demonstrating the utility of this methodology for the simultaneous arming and SAR studies of natural products.
To expand our group’s nucleophile catalyzed aldol lactonization (NCAL) reaction for synthesizing highly substituted cyclopentane fused beta-lactones, we developed a nucleophile catalyzed, tandem Michael aldol lactonization (NCMAL) reaction. Herein, we show the synthetic utility of this reaction in varying the Michael donors and acceptors, developing a catalytic, enantioselective NCMAL, and synthesizing tricyclic-!-lactones. Furthermore, we initiated studies toward applying this new methodology to the synthesis of a lipase inhibitor, vibralactone.