Dissertations / Theses on the topic 'Diversity-oriented synthesi'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 35 dissertations / theses for your research on the topic 'Diversity-oriented synthesi.'
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.
BONANDI, ELISA. "EXPLORATION OF THE CHEMICAL SPACE: DIVERSITY-ORIENTED AND CHEMOENZYMATIC APPROACHES." Doctoral thesis, Università degli Studi di Milano, 2020. http://hdl.handle.net/2434/704101.
Full textThis dissertation is an overview of a three-years project, aimed at the exploration of new regions of the chemical space, that could contain new unusual bioactive compounds. The already discovered small molecules cover only a small portion of the chemical universe, that becomes even narrower when bioactive compounds are considered. In this context, two different strategies for the investigation of the chemical space have been considered: the diversity oriented-synthesis (DOS), that constitute the major topic of the work, and a chemoenzymatic approach, developed during a period spent at the University of Warwick (UK), in the laboratory of Professor M. Tosin. Chapter 1 deals with the general principles of the DOS approach, focusing then the attention on a library of piperidine-based compounds previously synthesised in Professor Passarella’s research group, starting from a common precursor, 2-piperidine ethanol (1). An overview of the main results previously accessed in this field is reported. At the end of the chapter, the planning of a further expansion of this library is presented. The structure of the newly accessed piperidine-based products is appreciable in Figure 1 (see Figure 1 in the abstarct version reported in the thesis file); their obtainment was the main goal of this thesis. Chapter 2 is focused on the stereoselective synthesis of eight highly diversified polyheterocyclic compounds, characterized by three different scaffolds. In particular, the different scaffolds were originated by the same precursor, considering that its different syn- or anti- stereocenter configuration, influenced the reaction outcome. This project opens the possibility of accessing analogs of some natural products, such as lupin and lycopodium alkaloids. Chapter 3 concerned the obtainment of a library of potential Hedgehog (Hh) signalling pathway inhibitors, rationally designed exploiting docking simulations and taking inspiration from a class of natural products, the withanolides. The designed scaffold contains two key motif, a bicyclic carbamate and an α,β-unsaturated lactone, and presents three stereocenters. So far, two out of the four racemic isomers have been accessed and biological evaluation revealed two interesting intermediates, that have been synthesised also as separate enantiomers. Moreover, preliminary studies toward the obtainment of 2nd generation inhibitors have been performed in our laboratory. Biological evaluation of these compounds is currently in progress and will orient the future development of this work. Chapter 4 is aimed at the synthesis of (-)-anaferine as an unexpected further ramification of our DOS approach. Key intermediate 10, already exploited for the synthesis of the inhibitors of chapter 3, has been employed as starting material, converting its homoallylic alcohol into an α,β-unsaturated lactam. To this extent, the same approach used in chapter 1, to transform 9 into a similar lactam (left compound in the pink box of Figure 1) was applied. After that, the synthesis of (-)-anaferine was accomplished in few steps, reducing the lactam to piperidine and oxidizing the 2-hydoxypropane bridge to the corresponding ketone. Chapter 5 deals with the synthesis of thiocolchicine-based bivalent compounds, possibly acting as microtubules binders. A hybrid compound, bearing the key structural features of pironetin (one of the few known α-tubulin binder), previously synthesised on our laboratory from 2-piperidine ethanol, was exploited as key building block. In fact, it was connected through different linkers to N-10-deacteyl-thiocolchicine, a model of β-tubulin binder. Biological tests revealed that the lipophilic nature of the linkers rendered our conjugates better substrates for P-glycoprotein, leading to a drop in activity on resistant cancer cells. Therefore, new bivalent compounds will be soon produced in our laboratory, changing linkers chemo-physical properties. Structures of the new compounds resulting from the expansion of the DOS-approach from 2-piperidine ethanol 1. Finally, chapter 6 concerned a project aimed at the generation of unnatural, diversified derivatives of lasalocid A and salinomycin, through feeding experiments of malonate-mimicking chemical probes to the natural Streptomyces producers, in an approach resembling mutasynthesis. The efforts were focused on the devopment of different strategies for an easier recovery and analysis of the unnatural products from the complex mixtures of the fermentation broths. To this extent, four chemical probes have been synthesised and proof on concept experiments were performed to verify their applicability in this field.
Spandl, Richard Joseph. "Diversity oriented synthesis using enyne metathesis." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611971.
Full textNorth, Andrew James Peter. "Fragment synthesis : pharmacophore and diversity oriented approaches." Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/290076.
Full textMarineau, Jason Joseph. "New Applications of Cyclobutadiene Cycloadditions: Diversity and Target Oriented Synthesis." Thesis, Boston College, 2010. http://hdl.handle.net/2345/1741.
Full textCyclobutadiene cycloadditions provide rapid access to rigid polycyclic systems with high strain energy and unusual molecular geometries. Further functionalization of these systems allows entry into unexplored chemical space. A tricarbonylcyclobutadiene iron complex on solid support enables exploration of these cycloadditions in a parallel format amenable to diversity oriented synthesis. Modeling of the cycloaddition transition states with density functional calculations provides a theoretical basis for analysis of the regioselectivity observed in generation of these substituted bicyclo[2.2.0]hexene derivatives. The high strain energy accessible in cyclobutadiene cycloadducts and their derivatives renders them useful synthons for access to medium-ring natural products through ring expansion. Torilin, a guaiane sesquiterpene isolated from extracts of the fruits of Torilis japonica, exhibits a range of biological activities including testosterone 5α-reductase inhibition, hKv1.5 channel blocking, hepatoprotective, anti-inflammatory and anti-cancer effects. These activities are reviewed and analyzed from the perspective of a common biochemical target. Tandem oxidation and acid-catalyzed rearrangement of a highly strained tetracyclo[5.3.0.01,5.02,4]decane in the presence of tetrapropylammonium perruthenate provides the bicyclo[5.3.0]decane core of this natural product with complete control of relevant stereochemistry. The complex precursor required for this rearrangement is rapidly accessed by cyclopropanation of an intramolecular cyclobutadiene cycloadduct. Synthetic studies are reported which provide preliminary access to 8-deoxytorilolone
Thesis (PhD) — Boston College, 2010
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Chemistry
Torssell, Staffan. "Amino Aacohols : stereoselective synthesis and applications in diversity-oriented synthesis." Licentiate thesis, KTH, Chemistry, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-315.
Full textThis thesis is divided into three separate parts with amino alcohols as the common feature. The first part describes the development of a novel three-component approach to the synthesis of α-hydroxy-β-amino esters. Utilizing a highly diastereoselective Rh(II)-catalyzed 1,3-dipolar cycloaddition of carbonyl ylides to various aldimines, syn-α-hydroxy-β-amino esters formed in high yields and excellent diastereoselectivities. This methodology was also applied in a short enantioselective synthesis of the C-13 side-chain of Taxol.
The second part of the thesis describes a total synthesis of D-erythro- Sphingosine based on a cross-metathesis approach to assemble the polar head group and the aliphatic chain.
The last part deals with the application of amino alcohols as scaffolds in a diversity-oriented protocol for the development of libraries of small polycyclic molecules. The design of the libraries is based on the iterative use of two powerful ring-forming reactions; a ring-closing metathesis and an intramolecular Diels-Alder reaction, to simultaneously introduce structural complexity and diversity.
Leach, Stuart Grahame. "Diversity-Oriented Synthesis of Alkaloid-like Unnatural Products." Thesis, University of Leeds, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485593.
Full textMurrison, Sarah Louise. "Diversity-oriented synthesis of polycyclic alkaloid-like compounds." Thesis, University of Leeds, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.531520.
Full textCordier, Christopher James. "The Diversity-oriented Synthesis of Natural Product-like Libraries." Thesis, University of Leeds, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485204.
Full textQuevillon, Sophie. "Toward diversity-oriented synthesis of indoline-based polycyclic derivatives." Thesis, University of Ottawa (Canada), 2003. http://hdl.handle.net/10393/26425.
Full textThomas, Gemma Louise. "The search for novel antibacterials using diversity-oriented synthesis." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.612917.
Full textLepitre, Thomas. "Modulation des Processus Domino au départ des Accepteurs de Michael en série Chromone : Diversité par aza-Cyclisation, Arylation et Aryloxylation Métallocatalysées : Diversité par aza-Cyclisation, Arylation et Aryloxylation Métallocatalysées." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMLH31/document.
Full textIn the early 2000s a general consensus has emerged in which the molecular diversity within a given library of small molecules, rather than its size, has been recognized as a crucial requirement. Diversity-oriented synthesis (DOS) has emerged from this new paradigm. This novel approach aims to generate collections of small molecules with high degrees of structural diversity, in the most efficient way, starting from simple building-blocks. Since the generation of collections of structurally diverse small molecules in a DOS-driven approach constitutes a real challenge, diverse strategies have been set up for this purpose.In this line, this work has shed light on the great potential of a domino process as a valuable tool in a DOS-driven strategy, capable of generating both molecular diversity and architectural complexity. This study has been focused on the 3-formylchromone building block, a particular framework which has already proven being an exceptionally versatile precursor of molecular diversity. In this manuscript, we will highlight how it is possible to modulate the course of a domino process to achieve high degrees of molecular diversity, starting from the chromone based 1,6-Michael acceptors platform and primary amines as reaction partners. In particular we will show how it is feasible to control the course of particular steps involved in the domino process through: (I) the pertinent modulation of the Michael acceptors and the primary amines structures, (II) the modulation of the reaction parameters (solvent, temperature, additives), and (III) the tuning of the reactivity within a key reaction intermediate induced by the introduction of an external agent
O'Connell, Kieron Michael Geoffrey. "Strategy development for diversity-oriented synthesis : a two-directional macrocyclisation approach." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610161.
Full textMazraati, Tajabadi Fatemeh. "Identification of 3D Scaffolds Embedded in Natural Products and Synthesis of Focused Libraries." Thesis, Griffith University, 2017. http://hdl.handle.net/10072/365575.
Full textThesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Natural Sciences
Science, Environment, Engineering and Technology
Full Text
Cumaranatunga-Ilangasinghe, P. Kamani. "Stereocontrolled diversity oriented synthesis of 2H-benzopyran-based natural product-like polycyclics." Thesis, University of Ottawa (Canada), 2005. http://hdl.handle.net/10393/29208.
Full textSun, Li-Ping. "Syntheses of heterocyclic compounds via diversity-oriented approach and microwave-assisted solid-phase combinatorial chemistry /." View abstract or full-text, 2004. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202004%20SUN.
Full textMoulin, Emilie. "Diversity-oriented synthesis of pochonins : a privilege scaffold for ATPase and kinase inhibition." Université Louis Pasteur (Strasbourg) (1971-2008), 2006. https://publication-theses.unistra.fr/public/theses_doctorat/2006/MOULIN_Emilie_2006.pdf.
Full textPochonins A − F are six new members of the 14-membered resorcylic acid lactones (RALs) family which were identified in a Herpes Simplex Virus replication assay. Our interest in the pochonins stems from the observation that several other RALs are known to inhibit ATPases or kinases. Among them, radicicol was shown to be a potent inhibitor of HSP90 (Heat Shock Protein 90) whose activity is required for the functional maturation of a number of oncogenes, thus making this protein an attractive target for chemotherapy. A modular synthesis of pochonin C and its conversion to radicicol is presented. Both natural products are prepared in seven and eight steps, respectively, from three readily available fragments. Alternative syntheses of these compounds were also achieved using a combination of polymer-bound reagents and reactions on solid phase. Based on a molecular dynamics/minimization of radicicol and several known analogs, a correlation between the HSP90-inhibitory activity and the free energy of the bioactive conformer was established, leading to the identification of pochonin D as a potential inhibitor of HSP90. Its synthesis using polymer-bound reagents allowed us to confirm this finding and pochonin D was shown to be nearly as potent an HSP90 inhibitor as radicicol. Considering their closely-related structure, pochonin A was also synthesized and tested for HSP90 inhibition. The polymer-assisted chemistry developed for the pochonins syntheses enabled us to prepare a library based on the pochonin scaffold bearing five points of diversity, allowing us to extend beyond the modifications of the natural resorcylic acid lactones. Testing the library for its inhibition against a panel of 24 kinases at 10 µM and against HSP90 reveals several hits, thereby demonstrating the potential of the resorcylides towards the inhibition of therapeutically relevant kinases and ATPases. These syntheses of the pochonins were also the first reported in the literature allowing us to confirm structural assignments and to provide optical rotations as well as to define the stereochemistry of pochonin C’s carbon bearing the chlorine atom
Alcover, Charlotte. "Réseaux moléculaires et Chimie des Substances Naturelles : de l’isolement de composés inédits à de toutes nouvelles applications en synthèse biomimétique." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS569.
Full textThe discovery of new natural products is a very long and expensive process ; it is therefore important to detect previously known compounds in the studied matrices, to avoid an useless second isolation. This is the aim of annotation (partial but quick identification of compounds) and of dereplication (application of annotation to avoid reisolation).Thanks to its unequaled sensibility and to the "big data" era, the high performance liquid chromatography hyphenated to tandem mass spectrometry has become a reference technique in this field. Indeed, its use is generally implemented by informatic tools, as "molecular networking", because of the large amount of generated data.This thesis is divided into two parts : the first one deals with extraction of new compounds from a very well-known Apocynaceae plant, Picralima nitida. The second one is about the application of "molecular networking" to biomimetic chemistry in mixtures, especially about "3-alkylpiperidines" alkaloids
Krishna, Prasad Golla. "Synthesis of multicyclic 2-pyridones from a formyl and chlorometylene substituted precursor using a strategy of directed diversity-oriented synthesis." Thesis, Umeå universitet, Kemiska institutionen, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-56763.
Full textWang, Yikai. "Studies on Application of Silyl Groups in Ring-Closing Metathesis Reactions and Fragment-Based Probe Discovery." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10115.
Full textChemistry and Chemical Biology
Suzuki, Yamato. "Diversity-Oriented Syntheses of Fused Nitrogen Heterocycles and Their Application to the Structure-Activity Relationship Studies on CK2 Inhibitors." 京都大学 (Kyoto University), 2012. http://hdl.handle.net/2433/157893.
Full textSellstedt, Magnus. "Development of 2-Pyridone-based central fragments : Affecting the aggregation of amyloid proteins." Doctoral thesis, Umeå universitet, Kemiska institutionen, 2012. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-53705.
Full textGatbonton-Schwager, Tonibelle N. "Biological and Chemical Analysis of Small Molecule Activators of Anti-inflammatory and Antioxidant Nrf2-Keap1 Signaling." Case Western Reserve University School of Graduate Studies / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=case1390560628.
Full textNeves, dos Santos Ana Rita. "Exploration of [2+2+2] cyclotrimerisation reactions of alkynes : a new methodology for the synthesis of small molecules to probe biological systems." Thesis, University of Bradford, 2013. http://hdl.handle.net/10454/6311.
Full textGigant, Nicolas. "Synthèse et réactivité d'énamides, de la diversité moléculaire à la synthèse de molécules bioactives et/ou naturelles." Thesis, Orléans, 2012. http://www.theses.fr/2012ORLE2039.
Full textThe continuing demand to synthesize new and original collections of small molecules for the biological screening is an attractive subject for organic chemists and requires upstream the development of fast and easy synthetic methods. In this context, we decided to focus particularly on the functionalization of enamides which represent valuable building blocks in order to introduce nitrogen based functionality into various organic systems. Our objective was to synthesize new nitrogen containing compound libraries starting from common substrates by applying Diversity-Oriented Synthesis strategy and following these rules: atom economy, catalyzed reactions, fast synthesis in few steps and control of stereoselectivity. Firstly we mainly synthesized enamides. Thereafter, we developped efficient methodologies giving access to motifs frequently found in “privileged structures” or key scaffolds present in natural products or potential bioactive compounds thanks to various processes like aza-Michael, oxyamidation or cascade reactions, palladium chemistry with CH activation, dioxoazoborocanes or chiral auxiliary SAMP
Chou, Danny Hung-Chieh. "Small-Molecule Suppressors of Cytokine-Induced Beta-Cell Apoptosis." Thesis, Harvard University, 2011. http://dissertations.umi.com/gsas.harvard:10019.
Full textChemistry and Chemical Biology
Legault, Marc. "From Probes to Cell Surface Labelling: Towards the Development of New Chemical Biology Compounds and Methods." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20084.
Full textIgnatenko, Vasily A. "MOLECULAR LIBRARY SYNTHESIS USING NATURAL PRODUCTS: EXPANDING THE FRAMEWORK OF STEROIDS AND PENTACYCLIC TRITERPENOIDS." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1384382654.
Full textVoitovich, Iuliia. "Les inhibiteurs d'interaction protéine-protéine, une stratégie innovante en cancérologie." Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0701.
Full textBET-proteins, acting as epigenetic readers, play an essential role in cancer development. To date, numerous potent inhibitors disrupting BET functions have been discovered, including several of them that are undergoing clinical trials for the treatment of different types of cancer. The common drawback limiting their use in clinical practice is an inability to distinguish between BET-members that may cause side effects and resistances. The selective targeting of individual BET and the discrimination between BD1 and BD2 present an opportunity to achieve more selective transcriptional effect. A midthroughput screening of previously designed chemical library allowed identification of two molecules with unique profiles of selectivity that have never been observed. An undertaken structure-based program revealed a minimum scaffolds necessary for binding. Taking together with resolved X-Ray structures it allowed the development of more potent and selective BET inhibitors by DOTS (diversity oriented target focused synthesis) strategy, combining virtual screening and diversity oriented library design. This optimization led to a potent inhibitor with up to 100-fold improvement of affinity to the target and up to 300-fold selectivity toward BD1. Dose-response downregulation of c-Myc levels in low micromolar range in cell assays allowed the validation of the identified molecule as a chemical probe. Further comprehensive in vitro and in vivo evaluations of this compound will enable elucidating the biological role of each bromodomain and a validation of the interest toward the development of selective inhibitors in clinic
Elford, Timothy. "-exo-Alkylidene -lactones and -lactams via 2-alkoxycarbonyl allylboronates: mechanistic studies, diversity-oriented synthesis and target-oriented synthesis." Phd thesis, 2010. http://hdl.handle.net/10048/1021.
Full textSunderhaus, James Dennis. "The development of a four component reaction and its application to the synthesis of diverse heterocyclic scaffolds and the total synthesis of alkaloid natural products : the total synthesis of roelactamine and efforts towards the syntheses of rosicine and pseudotabersonine." Thesis, 2009. http://hdl.handle.net/2152/ETD-UT-2009-05-170.
Full texttext
Chen, Chan-Yu, and 陳湛于. "Design and Diversity-Oriented Synthesis of Benzimidazole Derivativesin Lead Drug Discovery." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/78603820159513812027.
Full textElford, Timothy Grant. "[Alpha]-exo-alkylidene [gamma]-lactones and [gamma]-lactams via 2-alkoxycarbonyl allylboronates mechanistic studies, diversity-oriented synthesis and target-oriented synthesis /." 2010. http://hdl.handle.net/10048/1021.
Full textTitle from pdf file main screen (viewed on June 25, 2010). In the title, the words alpha and gamma are represented by the Greek letters. A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy, Department of Chemistry, University of Alberta. Includes bibliographical references.
Pors, Klaus, F. W. Goldberg, C. P. Leamon, A. C. Rigby, S. A. Snyder, and Robert A. Falconer. "The changing landscape of cancer drug discovery: a challenge to the medicinal chemist of tomorrow." 2009. http://hdl.handle.net/10454/8821.
Full textSince the development of the first cytotoxic agents, synthetic organic chemistry has advanced enormously. The synthetic and medicinal chemists of today are at the centre of drug development and are involved in most, if not all, processes of drug discovery. Recent decreases in government funding and reformed educational policies could, however, seriously impact on drug discovery initiatives worldwide. Not only could these changes result in fewer scientific breakthroughs, but they could also negatively affect the training of our next generation of medicinal chemists.
Chen, Eric Kuan-Yu. "Verdazyl Radicals as Mediators in Living Radical Polymerizations and as Novel Substrates for Heterocyclic Syntheses." Thesis, 2010. http://hdl.handle.net/1807/24703.
Full textYao, Po-Hsin, and 姚伯昕. "1.Diversity-Oriented Synthesis of Coumarin-Linked Benzimidazoles via a One-Pot, Three-Step, Intramolecular Knoevenagal Cyclization 2.Multicomponent Reaction Synthesis of 2-aza-7-arylpyrrolizidine alkaloid Derivatives." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/5p73u6.
Full text國立交通大學
應用化學系碩博士班
105
First part:One-pot, three step synthesis of 3-(1-propyl-1H- benzo[d]imidazol-2-yl)-2H-chromen-2-one, using 2-cyano-N-(2-(propylamino)phenyl)acetamide compound 11 under p-toluene sulfonic acid catalyst to undergo intramolecular cyclization to form 2-(1-propyl-1H-benzo[d]imidazol-2-yl)acetonitrile compound 12, then add proper triethylamine to undergo Knoevenagel condensation reaction to get intermediate 14, and finally add 1N HCl to provide compound 15. Second part: Compounds 12 obtained in the first part of the study can further synthesize polycyclic structures to increase their biological activity and diversity, such as pyrazole. The compound 12, benzaldehyde 18 and piperidine are reacted in toluene to form the olefinic compound 23 and reacted with the phenylhydrazine compound 17 and cesium carbonate in an ethanol solution to give the product 1H-benzo [d] imidazole-1,3-diphenyl-1H-pyrazol-5-amine. Part 3: Synthesis of 2-aza-7-arylpyrrolidine alkaloid derivatives using a single non-mirror optical isomer. The intermediate 5-aryl thiohydantain 30 was first reacted with L-ester-based amino acid 32 and isothiocyanate 33 at room temperature for 30 minutes, followed by the addition of malononitrile , Benzaldehyde and piperidine at room temperature for 12 hours to give the product 2-aza-7-arylpyrrolididine 31.