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Tirosina, substrato em reações de acoplamento cruzado: síntese de dipeptídeos Tyr-Tyr, heterociclos e investigação da atividade biollógica contra células cancerígenas e parasitárias / Tyrosine, a building block in cross-coupling reactions: synthesis of dipeptides Tyr-Tyr, heterocycles and biological activity investigations against cancer cells and parasidic cellsVasconcelos, Stanley Nunes Siqueira 15 December 2017 (has links)
Tirosina, um aminoácido proteinogênico, de fundamental importância para nossa sobrevivência, foi objeto de estudo para a confecção da presente tese. Investigado frente às três reações de acoplamento cruzado mais exploradas nos últimos anos, Suzuki-Miyaura, Heck e Sonogashira, a 3-iodotirosina comportou-se como um excelente substrato na formação de unidades biarílicas, derivados estilbeno, formação de heterociclos do tipo 1,2,3-triazóis, quinolinas, benzofuranos e flavonas, bem como a formação de dipeptídeos Tyr-Tyr. A reação entre a 3-iodotirosina com diferentes nucleófilos de boro via reação de Suzuki- Miyaura, além de dar origem às unidades biarílicas, forneceu derivados do estilbeno, usados como substratos na construção de quinolinas, alcançadas por meio da reação multicomponente de Povarov, com catálise de prata em apenas 40 minutos sob irradiação de micro-ondas. Alguns desses derivados estilbeno, apresentaram ainda uma acentuada fluorescência, a qual foi medida em diferentes polaridades. Ao explorarmos a reação entre a 3-iodotirosina e acetilenos, derivados alquinílicos puderam ser convenientemente preparados, permitindo seu uso como materiais de partida na reação de cicloadição de Huisgen, no preparo de anéis triazólicos. Produtos provenientes da adição estereosseletiva de oxa-Michael, entre o anel fenólico da tirosina e aldeídos propargílicos, forneceram compostos carbonílicos α,β-insaturados capazes de reagirem via acoplamento intramolecular de Heck, levando a derivados 2-aril-3- formil-5-alanilbenzofuranos ou ainda, apenas alterando a atmosfera inerte de nitrogênio por monóxido de carbono, a formação de 2-aril-6-alanilflavonas via acilação intramolecular redutiva. Além da metodologia de síntese explorada na tese, alguns dos compostos obtidos apresentaram atividade biológica seletiva contra células de melanoma e leucemia, bem como atividade antiparasitária frente ao Plasmodium falciparum, não afetando a proliferação de células sadias. Dessa forma, os resultados apresentados, agregam ainda mais valor sintético e biológico ao aminoácido tirosina, explorados de forma inédita. / Tyrosine, a proteinogenic amino acid of fundamental importance for life, was the object of study for the research that is presented in this thesis. When 3-iodotyrosine was used in the three different types of cross-coupling reactions that have been exploited the most in recent years, namely the Suzuki-Miyaura, Heck and Sonogashira coupling reactions, 3-iodotyrosine as an excellent substrate for the formation of biaryl units, stilbene derivatives, 1,2,3-triazoletype heterocycles, quinolines, benzofurans and flavones, and Tyr-Tyr dipeptides. This work is organized into sections in order to facilitate ease of reading. The reaction between 3-iodotyrosine and different boron nucleophiles via the Suzuki- Miyaura coupling reaction, in addition to giving the biaryl units, also provided stilbene derivatives, which were used as substrates for the construction of quinolines via multicomponent Povarov reactions. The Povarov was performed with silver catalysis under 40 minutes of microwave irradiation. Some of these stilbene derivatives showed a marked fluorescence, which was measured in solvents with different polarities. By exploring the Sonogashira coupling reaction between 3-iodotyrosine and acetylenes, alkynyl derivatives could be conveniently prepared, which in turn could be used as starting materials in Huisgen cycloaddition reactions to synthesize1,2,3-triazole rings. Products from the stereoselective addition of oxa-Michael, between the phenolic ring of tyrosine and propargyl aldehydes, provided 945;,946;-unsaturated carbonyl compounds capable of reacting via Heck intramolecular coupling, leading to 2-aryl-3-formyl-5-alanylbenzofurans or by simply changing the inert atmosphere of nitrogen by carbon monoxide, the formation of 2- aryl-6-alanylflavones via reductive intramolecular acylation. In addition to the synthesis methodology explored in the thesis, some of the compounds showed selective biological activity against melanoma and leukemia cells, as well as antiparasitic activity against Plasmodium falciparum, without affecting the proliferation of healthy cells. In this way, the presented results add even more synthetic and biological value to the amino acid tyrosine, explored in an unprecedented way.
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Synthesis of Enantioenriched 1,5-Dienes and 1,5-Enynes by a Palladium-Catalyzed 3,3'-Reductive Elimination: Methodology Development and Mechanistic StudiesArdolino, Michael Joseph January 2014 (has links)
Thesis advisor: James P. Morken / This dissertation details the development, application and study of new palladium-catalyzed carbon-carbon bond forming strategies that generate synthetically useful enantioenriched small molecules. Controlled by a bidentate phosphine ligand, these transformations are thought to operate through a unique 3,3'-reductive elimination that leads to high regio- and stereoselectivity. Specifically, Chapter 1 introduces background on prior work that led to the first allyl-allyl coupling to deliver branched 1,5-dienes, and presents new computational studies on the origins of regioselectivity with mono- and bidentate ligands. Building on these studies, Chapter 2 describes the development of a diastereoselective allyl-allyl coupling of substituted allylboron reagents with allylic chloride electrophiles. To extend the scope of allyl-allyl coupling, Chapter 3 details further reaction optimization and mechanistic studies that have allowed for increasingly congested bond formations. In Chapter 4, a related allyl-propargyl coupling to give enantioenriched 1,5-enynes through stereospecific reactions and kinetic resolution is presented. These developments are accompanied by laboratory and computational data that provide a deeper understanding of reaction mechanisms and the origins of regio- and stereoselectivity. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
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Catalytic Conjunctive Cross-Coupling and Catalytic Diboration ReactionsZhang, Liang January 2017 (has links)
Thesis advisor: James P. Morken / This dissertation will present four main projects focused on stereoselective construction of borylated compounds as well as their applications in asymmetric syntheses. The first two projects describe the development of a catalytic conjunctive cross-coupling reaction. By merging three simple starting materials, an organolithium reagent, an organoboronate, and an organic electrophile, a synthetically valuable secondary boronate is furnished by the conjunctive cross-coupling in an efficient and enantioselective fashion. Next, this strategy is expanded to synthesize severely hindered tertiary boronates, a synthetic challenging but powerful building block to access a variety of quaternary stereocenters. The third project presents a platinum-catalyzed enantioselective diboration of alkenyl boronates to furnish a broad range of 1,1,2-tris(boronates) products. A deborylative alkylation of the 1,1,2-tris(boronates) leads to a variety of internal vicinal bis(boronates) with high diastereoselectivity. In the final chapter, a general and practical synthesis of alkenyl boronates via the boron-Wittig reaction is disclosed. Utilizing readily accessible geminal bis(boronates) and aldehydes, a broad range of disubstituted and trisubstituted alkenyl boronates are afforded with good yield and stereoselectivity. / Thesis (PhD) — Boston College, 2017. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
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Tirosina, substrato em reações de acoplamento cruzado: síntese de dipeptídeos Tyr-Tyr, heterociclos e investigação da atividade biollógica contra células cancerígenas e parasitárias / Tyrosine, a building block in cross-coupling reactions: synthesis of dipeptides Tyr-Tyr, heterocycles and biological activity investigations against cancer cells and parasidic cellsStanley Nunes Siqueira Vasconcelos 15 December 2017 (has links)
Tirosina, um aminoácido proteinogênico, de fundamental importância para nossa sobrevivência, foi objeto de estudo para a confecção da presente tese. Investigado frente às três reações de acoplamento cruzado mais exploradas nos últimos anos, Suzuki-Miyaura, Heck e Sonogashira, a 3-iodotirosina comportou-se como um excelente substrato na formação de unidades biarílicas, derivados estilbeno, formação de heterociclos do tipo 1,2,3-triazóis, quinolinas, benzofuranos e flavonas, bem como a formação de dipeptídeos Tyr-Tyr. A reação entre a 3-iodotirosina com diferentes nucleófilos de boro via reação de Suzuki- Miyaura, além de dar origem às unidades biarílicas, forneceu derivados do estilbeno, usados como substratos na construção de quinolinas, alcançadas por meio da reação multicomponente de Povarov, com catálise de prata em apenas 40 minutos sob irradiação de micro-ondas. Alguns desses derivados estilbeno, apresentaram ainda uma acentuada fluorescência, a qual foi medida em diferentes polaridades. Ao explorarmos a reação entre a 3-iodotirosina e acetilenos, derivados alquinílicos puderam ser convenientemente preparados, permitindo seu uso como materiais de partida na reação de cicloadição de Huisgen, no preparo de anéis triazólicos. Produtos provenientes da adição estereosseletiva de oxa-Michael, entre o anel fenólico da tirosina e aldeídos propargílicos, forneceram compostos carbonílicos α,β-insaturados capazes de reagirem via acoplamento intramolecular de Heck, levando a derivados 2-aril-3- formil-5-alanilbenzofuranos ou ainda, apenas alterando a atmosfera inerte de nitrogênio por monóxido de carbono, a formação de 2-aril-6-alanilflavonas via acilação intramolecular redutiva. Além da metodologia de síntese explorada na tese, alguns dos compostos obtidos apresentaram atividade biológica seletiva contra células de melanoma e leucemia, bem como atividade antiparasitária frente ao Plasmodium falciparum, não afetando a proliferação de células sadias. Dessa forma, os resultados apresentados, agregam ainda mais valor sintético e biológico ao aminoácido tirosina, explorados de forma inédita. / Tyrosine, a proteinogenic amino acid of fundamental importance for life, was the object of study for the research that is presented in this thesis. When 3-iodotyrosine was used in the three different types of cross-coupling reactions that have been exploited the most in recent years, namely the Suzuki-Miyaura, Heck and Sonogashira coupling reactions, 3-iodotyrosine as an excellent substrate for the formation of biaryl units, stilbene derivatives, 1,2,3-triazoletype heterocycles, quinolines, benzofurans and flavones, and Tyr-Tyr dipeptides. This work is organized into sections in order to facilitate ease of reading. The reaction between 3-iodotyrosine and different boron nucleophiles via the Suzuki- Miyaura coupling reaction, in addition to giving the biaryl units, also provided stilbene derivatives, which were used as substrates for the construction of quinolines via multicomponent Povarov reactions. The Povarov was performed with silver catalysis under 40 minutes of microwave irradiation. Some of these stilbene derivatives showed a marked fluorescence, which was measured in solvents with different polarities. By exploring the Sonogashira coupling reaction between 3-iodotyrosine and acetylenes, alkynyl derivatives could be conveniently prepared, which in turn could be used as starting materials in Huisgen cycloaddition reactions to synthesize1,2,3-triazole rings. Products from the stereoselective addition of oxa-Michael, between the phenolic ring of tyrosine and propargyl aldehydes, provided 945;,946;-unsaturated carbonyl compounds capable of reacting via Heck intramolecular coupling, leading to 2-aryl-3-formyl-5-alanylbenzofurans or by simply changing the inert atmosphere of nitrogen by carbon monoxide, the formation of 2- aryl-6-alanylflavones via reductive intramolecular acylation. In addition to the synthesis methodology explored in the thesis, some of the compounds showed selective biological activity against melanoma and leukemia cells, as well as antiparasitic activity against Plasmodium falciparum, without affecting the proliferation of healthy cells. In this way, the presented results add even more synthetic and biological value to the amino acid tyrosine, explored in an unprecedented way.
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Low cost, more efficient, and less toxic synthetic routes to conjugated polymersAyuso Carrillo, Josue January 2016 (has links)
As key components of flexible organic electronics, the synthesis of polythiophenes via less toxic and more cost-effective routes is demanded. An efficient synthetic route for the production of thienyl-containing homopolymers and copolymers has been developed. The synthetic approach consists of: i) the synthesis in high yield and high purity of thienyl borane monomers protected with N-methyliminodiacetic acid (MIDA) via C-H electrophilic borylation. This reaction uses a combination of inexpensive reagents BCl3, AlCl3, and 2,6-dichloropyridine (Cl2Py) for the regioselective electrophilic aromatic substitution of thiophenes, followed by addition of a second aprotic amine pre-esterification to reduce the Brønsted acidity of the reaction mixture. In situ esterification provided the desired thienyl MIDA boronateester monomers in one-pot at room temperature. ii) Subsequent Suzuki-Miyaura polymerisation of the synthesised monomers to produce well defined thienyl containing pie-conjugated polymers in high molecular weight and high yields. Key reaction parameters for successful Suzuki-Miyaura polymerisation of thienyl-derived MIDA boronate esters under mild temperatures (i.e., 55 °C in THF) were found: a) an optimal monomer:H2O:base ratio, which enables controlled hydrolysis of the BMIDA moiety into its corresponding boronic acid at appropriate rates for high fidelity polymerisation. b) Nature of the base, where K3PO4 provided the best results for production of homopolymers (e.g., rr-P3HT), or KOH which gave excellent results for the formation of copolymers across a range of electronically different comonomers (e.g., pCPDT-BT). Thus, it is demonstrated that the approach is a general strategy for the highly efficient production of thienyl containing pie-conjugated regioregular, regiosymmetric and Donor-Acceptor polymers.
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Contribuição ao estudo de reações mediadas por calcogenetos Zn e Cu: hidrocalcogenação de ácidos e ésteres e síntese de sulfetos arílicos / New contributions for the synthesis of unsymmetrical diaryl thioethers and vinyl chalcogenides compunds promoted by copper Senelenophene-2-carboxylate and zinc chalcogenolatesNunes, Vanessa Loren 04 May 2012 (has links)
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Previous issue date: 2012-05-04 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / This work describes some studies on the preparation of unsymmetrical
diaryl thioethers catalyzed by Copper(I)-Senelenophene-2-carboxylate. The
results concern to the catalyzed cross-coupling reaction between aryl halides
and aryl or alkylthiols using Copper(I)-Senelenophene-2-carboxylate (CuSC) a
new Cu-catalyzed one-pot protocol. The products were obtained in good to
excellent yields under relatively mild reaction conditions presenting
chemoselectivity and functional group tolerance. Additionally, we have developed a chemio-, regio and stereoselective
synthesis of vinyl chalcogenides compounds promoted by zinc chalcogenolates.
In this protocol the reductive cleavage of chalcogen bond by the Zn/NH4OH
system led to zinc chalcogenolates. The reaction was carried out with acids and
esters propiolics afford β-chalcogenacrillic acids and esters under mild and
basic conditions. The stereochemistry corresponding to anti-Markovnikov
addition of the chalcogenolate constituents across the triple bond were obtained
in good yields. / Este trabalho descreve o estudo das reações de acoplamento cruzado
entre iodetos arílicos e tióis arílicos ou alquílicos catalisada por 2-carboxilato
selenofeno de cobre (I) (CuSC). Apresentamos uma nova metodologia “ one
pote” para a síntese de tioésteres arílicos obtidos em condições reacionais
relativamente brandas, apresentando quimiosseletividade, tolerância a diversos
grupos funcionais e rendimentos que variam entre bons a ótimos (70-100%).
R1I + R2SH
K3PO4, DMSO
S
R1 R2
Adicionalmente, desenvolvemos uma síntese quimio, régio, e
estereosseletiva de compostos vinil calcogenetos promovida por calcogenolato
de zinco. Neste protocolo a clivagem redutiva da ligação calcogênio feita pelo
sistema Zn/NH4OH obteve os calcogenolatos de zinco. A reação foi realizada
com ácidos e ésteres propiólicos formando ácidos acrílicos β-calcogênio e
ésteres sob condições básicas e brandas. A estereoquímica corresponde a
adição anti-Markovnikov dos constituintes calcogenolatos através da ligação
tripla. Os calcogenetos vinílicos foram obtidos em bons rendimentos (40-96).
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Transition metal catalysis : a new paradigm in bioorthogonal drug activationClavadetscher, Jessica Veronica January 2017 (has links)
Powerful tools have emerged in the past few years to allow the sensing, imaging and modulation of biological processes in living systems. Bioorthogonal organometallic reactions are transformations catalysed by transition metals, which are compatible within a biological environment. Palladium-mediated cross-coupling and decaging reactions, for example, have been successfully applied to catalyse non-natural chemical transformations within a biological milieu. Up until now, copper-catalysed cycloaddition reactions have been used extensively for the conjugation, immobilisation, and purification of biomolecules, but their further application in vivo has been limited by the inherent toxicity of copper. Herein, different transition metal catalysts were designed and applied in cellular and in vivo manipulations. Polymeric solid supports were functionalised with palladium nanoparticles and used as biocompatible, heterogeneous catalysts in selective decaging and cross-coupling reactions to activate fluorescent probes and synthesise cytotoxic anticancer drugs in situ. In order to gain tumour selectively, targeting functionalities were incorporated into the particles to allow the spatial control of the selective activation of labelling probes. The simultaneous synthesis of two different anticancer agents intracellularly, by two totally different mechanisms (in situ synthesis and decaging), is reported. The cellular toxicity of copper was addressed by entrapping copper nanoparticles on a polymeric solid support, allowing the activation of labelling probes, as well as the synthesis of an anticancer agent from two benign components through the well-known copper catalysed azide-alkyne cycloaddition. The biocompatibility of the copper catalysts in vivo was shown by implantation in zebrafish embryos.
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Synthesis and Applications of Chiral Phosphoramidites Copper(II) and Silver(I) Complexes as Catalysts in Asymmetric SynthesisCastelló Moncayo, Luis Miguel 05 June 2015 (has links)
No description available.
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Development and Investigation of Electrocyclization Reactions Leading Towards Indene and Thiatriazole Formation and their FunctionalizationRosocha, Yaroslav Gregory S. 19 January 2012 (has links)
No description available.
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Applications of B-Lactones: Utility of Spiroepoxy-B-Lactones and Development of a Double Diastereoselective Nucleophile Catalyzed, Aldol-Lactonization Process Leading to !-Lactone Fused Carbocycles and TetrahydrofuransMorris, Kay A. 2010 August 1900 (has links)
Natural products continue to inspire synthetic chemists to develop novel
methodologies to provide efficient and expedient syntheses of the target molecules.
Haterumalide NA aroused our interest and prompted development of four differing
methodologies. Three of the strategies pursued involved use of B-lactone scaffolds as
intermediates. Extensions of the nucleophile catalyzed, aldol-lactonization (NCAL)
reaction were also pursued and targeted toward alternative natural product targets.
The reactivity of the unexpectedly stable strained spirocycle, spiroepoxy-B-
lactone, was explored. Spiroepoxy-B-lactones exhibited a wide range of reactivity, but
largely rearranged to tetronic acids. The desired reaction manifold remained inaccessible
and led to application of the NCAL process to tetrahydrofuran-fused B-lactones. Several
tetrahydrofuran-fused B-lactones were prepared, which displayed low
diastereoselectivity. The diastereoselectivity could be somewhat improved in a double
diastereoselective NCAL process with varied solvent systems, yet the carbocyclic
analogues gave much more promising results. The use of carbocycle-fused !-lactones
ultimately culminated in a double diastereoselective NCAL process, and overall led to improvements in diastereoselectivities from 1:1-2 up to >19:1. Further expansion of the
substrate scope for the NCAL process was studied for application to bridged tricyclic B-
lactones, access to carbocycle-fused y-lactones, and towards development of a dynamic
kinetic resolution NCAL process.
With our interest aimed at haterumalide NA, a modified Negishi cross coupling
between zincates and dichloroolefins was also revisited. The stringent anhydrous
reaction conditions led to reexamination of initial leads, which provided user-friendly
anhydrous conditions by utilizing commercially available anhydrous solvent. However,
application was implemented solely to a simplified model system.
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