Total synthesis of natural products with diverse architecture and varying degree of complexity is an area that has not only inspired and attracted several generations of organic chemists but also continues to enrich and refresh the foundations of organic chemistry itself, by offering new ideas and directions. Synthetic organic chemistry is perhaps the most formative and expressive enterprise of science in terms of its creative power and unlimited scope. Its impact on present day life and prosperity gets manifested when we see this science as the bedrock behind the production of pharmaceuticals, pesticides, fertilizers, nutritional products, high tech materials, polymers, cosmetics, plastics and clothing. Science of synthesis is also going to play an important role in the evolution of future societies based on the principles of the sustainable development. Being a precise science and a fine art, the endeavor of total synthesis is in a constant state of effervescence. Most significantly, the discipline is being continually challenged by new structures unraveled from the Nature’s bosom. The practice of total synthesis is being enriched constantly by new tools such as new reagents and catalysts as well as by analytical techniques. In fact, there has been a dramatic advancement in the recent past in the development of new synthetic protocols with high regio-, streo-, and enantiocontrol, which makes it possible to target natural product of any complexity. The demand for enantiomerically pure drugs, agrochemicals and food additives is growing, since pure enantiomers are often more target-specific and have fewer side effects than the recemic mixtures. As a result, synthesis of natural products in an enantioselective manner has been receiving increasing attention from synthetic chemists in recent years. Nature synthesizes a vast array of novel molecular structures in enantioselective fashion through several well-established biosynthetic pathways utilizing a few key building blocks. Among them mevalonate pathway to terpenes, shikimate pathway to aromatics, alkaloids and the polyketide pathway to aromatics, macrolides and related compounds are the most noteworthy. Polyketides, constitutes a large family of natural products built from acyl coenzyme A monomers and exhibit remarkable diversity both in terms of their structure and function. These natural products display a wide range of medicinally important activities such as antibiotic, anticancer, antifungal, hypolipidemic and immunosuppressive properties. In recent years, polyketide derived natural products embodying an epoxyquinone core, have been surfacing with increasing frequency from diverse natural sources. Both on account of their structural diversity and promising biological activity, polyketide derived epoxyquinoid natural products have evoked considerable attention from the synthetic community during the past few years. We too got enticed towards these natural products as an offshoot of ongoing research activity in the group. The present thesis entitled “Enantioselective Total Synthesis of Bioactive Epoxyquinoid Natural Products” is described in four chapters. Chapter 1: Enantioselective total synthesis of (+)-eupenoxide, (+)-6-epi-eupenoxide and (+)-phomoxide; Chapter 2: Enantioselective total synthesis of (−)-EI-1941-2; Chapter 3: Enantioselective total synthesis of (+)-integrasone. Chapter 4: Enantioselective total synthesis of (+)-hexacyclinol. It’s quite tempting to highlight the fact that while Nature might have used entirely different biochemical machinery to build up all these diverse natural products; but in the chemical laboratory all the syntheses have emanated from a single starting material, symbolizing the intrinsic power and versatility of chemical synthesis.

Bicyclic dihydrothiazolo fused 2-pyridones have been studied as a new class of antibacterial agents, termed pilicides, that target the formation of adhesive bacterial surface organelles (pili) in pathogenic bacteria. Synthetic methods to further functionalize the bicyclic 2-pyridone scaffold have been developed in order to increase water-solubility and thereby facilitate biological evalua-tions. This was accomplished by introducing aminomethylenes at the open position C-6. Tertiary amines were introduced via a microwave–assisted Mannich reaction and a synthetic route based on a formyl intermediate gave access to primary, secondary and tertiary amines, but also to other interesting functionalities. Biological evaluation confirmed that several of the function-alized compounds inhibited pili formation in uropathogenic E. coli., as dem-onstrated by assays of hemagglutination, biofilm formation and adherence to bladder cells. Co-crystallizing one of the pilicides with the target protein gave information about the binding site and based on this a mechanism of action was proposed, which was supported experimentally by surface plas-mon resonance and single point mutations in the protein. Furthermore, the previously developed acylketene imine reaction used to prepare bicyclic thiazolo fused 2-pyridone pilicides has been developed to allow preparation of other ring-fused 2-pyridone systems. Benzo[a]quinolizine-4-ones and indolo[2,3-a]quinolizine-4-ones could be prepared in a fast and simple manner starting from dihydroisoquinolines and a β-carboline. Finally, this method could also be applied for the preparation of heteroatom analogs of the previously studied sulfur containing pilicides. Biological evaluations established that the sulfur atom can be replaced by oxygen and still maintain the ability to prevent pili assembly.

The thesis entitled “Enantioselective synthesis of didemniserinolipid, cladospolides, aspercyclide and muricatacin” is divided into three chapters. First chapter of the thesis deals with the formal total synthesis both enantiomers didemniserinolipid B from L-(+)-tartaric acid. Fused bicyclic acetals containing 6,8-dioxabicyclo[3.2.1]octane structural unit are wide spread in bio active natural products. Didemniserinolipids A-C possessing similar framework were isolated from a methanol extract of Didemnum sp., and some of the analogous compounds were found to be cytotoxic against P388, A549, and HT29 tumor cell lines. Pivotal reactions en route to the natural product include the elaboration of a γ-hydroxy amide derived from tartaric acid, olefin cross metathesis and Wittig olefination (Scheme 1). (+)-didemniserinolipid B Scheme 1: Retrosynthesis of both enantiomers of didemniserinolipid B. Second chapter of the thesis describes an enantiodivergent synthesis of macrolactones: In section A, enantiodivergent approach for the synthesis of cladospolides B, C and iso-cladospolide B is described. The cladospolides A-D are a class of 12-membered macrolactones, isolated from various cladosporium species of fungi and posseses a range of biological activities. Key reaction in the synthetic sequence involve formation of the required side chain by olefin cross metathesis. Selective Wittig olefination and lactonization afforded cladospolides (Scheme 2). Scheme 2: Enantiodivergent synthesis of cladospolide B, C and iso-cladospolide B. In section B, synthesis of bio-active biaryl ether lactone aspercyclide is described. Aspercyclides A-C are 11-membered biaryl ether lactones isolated from the extraction of the fermentation broth of an Apergillus. Sp.. Aspercyclides are reported to be moderately active (IC50 of 200 M for aspercyclide A) in the IgE receptor binding, which is key for the understanding of allergic disorders. A combination of Boord elimination and Mitsunobu reactions were employed to synthesize the key homoallylic alcohol from γ-hydroxy amide derived from tartaric acid. Elaboration of γ-hydroxy amide derived from L-(+)-tartaric acid is the key step for the synthesis of both enantiomers of the chiral homoallylic alcohol part, while Ullmann coupling reaction is employed to construct biaryl linkage. Ring closing metathesis (RCM) of the diene furnished required macrolactone (Scheme 3). Scheme 3: Enantiodivergent formal total synthesis of aspercyclide C. Last chapter of the thesis describes the enantioselective synthesis of muricatacin, a bio-active butanolide isolated as the major component of a scalemic mixture from the seeds of Annona muricata. Muricatacin was found to exhibit potent cytotoxicity toward several human tumor cell lines with SAR studies showing that activity is influenced significantly by the nature of the side chain. Stereoselective synthesis of ()-Muricatacin and structurally similar butanolide L-Factor has been accomplished from L-(+)-tartaric acid. Pivotal strategy in the synthesis is the elaboration of -hydroxy amide to the required allylic alcohol which on further reactions (including RCM) provided muricatacin (Scheme 4). Scheme 4: Stereoselective synthesis of Muricatacin and L-Factor. (For structural formula pl refer the thesis)

Made available in DSpace on 2015-07-22T20:50:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-02-27. Added 1 bitstream(s) on 2015-08-11T03:25:51Z : No. of bitstreams: 1 Publico-10940a.pdf: 1658831 bytes, checksum: ef7d2834f9c77439f22a6b2da7c722c7 (MD5). Added 1 bitstream(s) on 2015-08-11T03:25:52Z : No. of bitstreams: 2 Publico-10940a.pdf: 1658831 bytes, checksum: ef7d2834f9c77439f22a6b2da7c722c7 (MD5) Publico-10940b.pdf: 1216468 bytes, checksum: bd1ea49c2bfdfa8789e58924c9513820 (MD5) / Nesta dissertação, são descritos os estudos visando a síntese total da isodolastatina H, um éster peptídico natural da família das dolastatinas com grande atividade citotóxica. O diferencial nesta sintese sobre as outras, foi a construcao das unidades gama-aminoacidos Dil e Dap, que foram obtidas via reacao de adicao de sais de crotil e aliltrifluoroboratos a L -prolinal e L -valinal, respectivamente. Os fragmentos foram posteriormente unidos por reacoes de esterificacao e amidacao. / This dissertation, are described the study towards to total synthesis of isodolastatin H, a natural peptide ester of dolastatin family with great citotoxicity activity. The main focus in this synthesis, is the construction of gama-aminoacid units Dil and Dap, obtained via addition reaction of crotyl and allyltrifluoroborate salts with L -prolinal and L-valinal, respectively. The junction of fragments was subsequently made from esterification and amidation reaction. / TEDE / BV UNIFESP: Teses e dissertações

Orientador: Prof. Dr. Anderson Orzari Ribeiro / Dissertação (mestrado) - Universidade Federal do ABC. Programa de Pós-Graduação em Ciência e Tecnologia/Química, 2015. / Neste trabalho foram obtidos dez compostos derivados de fenóis, sendo eles o 2-hidroxi-5-nitro-benzaldeído, (AQ-1), 2-hidroxi-3-nitro-benzaldeído, (AQ-2), 1-(2,4-dihidroxi-3-nitro-fenil)-etanona (HMQ-1), 1-(2,4-dihidroxi-3,5-dinitro-fenil)-etanona (HMQ-2), 2-(3-metilbut-2-eniloxi)-benzaldeído, (MP-1), 1-(3-metilbut-2-eniloxi)-2-(2-nitrovinil)-benzeno, (MP-2), 2-[2-(3-metil-but-2-eniloxi)-benzilideno]-malononitrila, (MP-3), 2-(furan-2-carbonil)-3-[2-(3-metil-but-2-eniloxi)-fenil]-acrilonitrila, (AQ-12), 2-(3-metil-but-2-eniloxi)-5-nitro-benzaldeído, (AQ-3) e 1-(3-metil-but-2-eniloxi)-4-nitro-2-(2-nitro-vinil)-benzeno, (AQ-6). Para a obtenção dos compostos foram empregados diversos métodos sintéticos. Destaca-se a obtenção dos compostos AQ-1, AQ-2 e HMQ-1 pelo método de nitração direta sem a utilização de catalisadores, do composto HMQ-2 que possui dois substituintes nitro no anel aromático, dos compostos MP-1 e MP-2 obtidos por micro-ondas o que diminui drasticamente o tempo de obtenção destas moléculas e do composto AQ-6, análogo estrutural do MP-2 que possui um substituinte nitro no anel aromático, o que confere a molécula características eletrônicas diferentes ao do seu antecessor. Os produtos obtidos foram caracterizados mediantes diferentes métodos de caracterização, entre eles a espectroscopia de absorção infravermelho, massa, RMN-1H e 13C, DEPT e de duas dimensões 1H,1H COSY, 1H,1H NOESY e 1H,13C espectro combinatório (HSQC, HMBC). O composto MP-2, obtido a partir da síntese Knoevenagel do composto MP-1 com nitrometano, apresentou significativa atividade antitumoral seletiva, sendo 4,64 vezes mais ativo frente as células tumorais do que as células sadias e ação antimetastática, inibindo por completo o processo de migração das células tumorais nas diferentes concentrações testadas. / In this study were obtained ten phenol derivatives, 2-hydroxy-5-nitrobenzaldehyde, (AQ-1), 2-hydroxy-3-nitrobenzaldehyde (AQ-2), 1-(2,4-dihydroxy-3-nitro-phenyl)-ethanone (HMQ-1), 1- (2,4-dihydroxy-3,5-dinitro-phenyl)-ethanone (HMQ-2) 2-(3-methylbut-2-enyloxy)benzaldehyde, (MP-1), 1-(3-methylbut-2-enyloxy)-2-(2-nitrovinyl)benzene, (MP-2), 2-[2-(3-methyl-but-2-enyloxy)benzylidene]-malononitrila (MP-3), 2-(furan-2-carbonyl)-3-[2-(3-methyl-but-2-enyloxy)-phenyl]-acrilonitrila, (AQ-12), 2-(3-methyl-but-2-enyloxy)-5-nitrobenzaldehyde (AQ-3) and 1- (3-methyl-but-2-enyloxy)-4-nitro-2-(2-nitro-vinyl)benzene (AQ-6). Various synthetic methods were employed to obtain the compounds, as such, ultrasound bath, microwave reactor and agitation plate. Noteworthy is the achievement of AQ-1 compounds, AQ-2 and HMQ-1 by direct nitration method without the use of catalysts, the HMQ-2 compound having two nitro substituents on the aromatic ring, the MP-1 compounds and MP-2 using microwave-oven which dramatically reduces the reaction time for obtaining these molecules and AQ-6 compound structural analogue of the MP-2, but having a nitro substituent on the aromatic ring, which gives the molecule different electronic characteristics to that of its predecessor. The products obtained were characterized by the use of different spectroscopic methods in different centers, highlighting the characterization carried out in Germany Rostock. The employer spectroscopic methods were: infrared absorption spectroscopy, mass spectrometry, 1H-NMR and 13C-NMR spectroscopy, DEPT and two-dimensional 1H, 1H COSY, 1H, 1H NOESY and 1H, 13C combinatorial spectra (HSQC, HMBC). The MP-2 compound obtained from the Knoevenagel synthesis of MP-1 compound and nitromethane, showed significant selective antitumor activity and antimetastatic action of tumor cells.

Bacteria are known to release a large variety of small molecules known as autoinducers (AI) which effect quorum sensing (QS) initiation. The interruption of QS effects bacterial communication, growth and virulence. Three novel classes of S-ribosylhomocysteine (SRH) analogues as potential inhibitors of S-ribosylhomocysteinase (LuxS enzyme) and AI-2 modulators of QS were developed. The synthesis of 2-deoxy-2-bromo-SRH analogues was attempted by coupling of the corresponding 2-bromo-2-deoxypentafuranosyl precursors with the homocysteinate anion. The displacement of the bromide from C2 rather than the expected substitution of the mesylate from C5 was observed. The synthesis of 4-C-alkyl/aryl-S-ribosylhomocysteine analogues involved the following steps: (i) conversion of the D-ribose to the ribitol-4-ulose; (ii) diastereoselective addition of various alkyl or aryl or vinyl Grignard reagents to 4-ketone intermediate; (iii) oxidation of the primary hydroxyl group at C1 followed by the intramolecular ring closure to the corresponding 4-C-alkyl/aryl-substituted ribono-1,4-lactones; (iv) displacement of the activated 5-hydroxyl group with the protected homocysteinate. Treatment of the 4-C-alkyl/aryl-substituted SRH analogues with lithium triethylborohydride effected reduction of the ribonolactone to the ribose (hemiacetal) and subsequent global deprotection with trifluoroacetic acid provided 4-C-alkyl/aryl-SRHs. The 4-[thia]-SRH were prepared from the 1-deoxy-4-thioribose through the coupling of the α-fluoro thioethers (thioribosyl fluorides) with homocysteinate anion. The 4-[thia]-SRH analogues showed concentration dependent effect on the growth on las (50% inhibitory effect at 200 µg/mL). The most active was 1-deoxy-4-[thia]-SRH analogue with sufur atom in the ring oxidized to sulfoxide decreasing las gene activity to approximately 35% without affecting rhl gene. Neither of the tested compounds had effect on bioluminescence nor on total growth of V. harveyi, but had however slight inhibition of the QS.

Les substances naturelles ont toujours joué un rôle important dans la recherche de nouvelles molécules d’intérêt thérapeutique. Ces produits peuvent être aussi utilisés comme sondes dans l’étude de systèmes biologiques et améliorer notre compréhension de ces phénomènes. Toutefois, la grande majorité des librairies de molécules synthétisées en chimie médicinale dans l’industrie pharmaceutique ou dans la recherche académique sont composées de molécules possédant des squelettes hétérocycliques qui couvrent une faible partie de l’espace des molécules pouvant être potentiellement découvertes (estimation de 1060 molécules organiques sous les 500 Da). Dans ce mémoire, nous décrivons la synthèse de nouvelles librairies de molécules basées sur des squelettes de produits naturels. Ces entités possèdent un niveau de complexité et de diversité élevé. Différentes stratégies ont été développées durant cette thèse dans le but de synthétiser avec efficacité des librairies possédant ces caractéristiques: synthèse divergente de nouveaux squelettes polycycliques catalysée par des métaux de transition, synthèse de dérivés de produits naturels décorés de façon à moduler leur activité biologique et synthèse de librairies encodées avec des acides peptido-nucléiques. / Natural products have played a key role in the search for new drugs. These bioactive molecules can also be used as probes in biological studies and expand our knowledge of the mechanisms involved. Nevertheless, the large majority of chemical libraries currently synthesized in pharmaceutical companies or in academic research centers consist of heterocyclic scaffolds which cover a small part of the available chemical space (1060 molecules below 500 Da). In this dissertation, we describe the synthesis of new libraries based on natural product scaffolds. They present a high level of complexity and diversity. Creative strategies used to quickly generate these libraries have been developed during this PhD such as the divergent synthesis of new polycyclic scaffolds catalyzed by transition metals, the synthesis of terpene derivatives functionalized in order to modulate their biological activity, and the PNA encoded synthesis of small molecules libraries.

Orientadora: Profa. Dra. Mirela Inês de Sairre / Dissertação (mestrado) - Universidade Federal do ABC. Programa de Pós-Graduação em Ciência e Tecnologia/Química, 2017. / As licochalconas estão naturalmente presentes na raiz de Glycyrrhiza inflata (alcaçuz) e apresentam atividades biológicas, como antitumoral, antiparasitária, anti-oxidativa e bactericida. A licochalcona "A" apresentou atividade anti-leishmania, o que despertou o interesse em investigar e testar o uso para tratamento da leishmaniose visceral canina (LVC), uma zoonose grave que atinge os cães domésticos, os quais são sacrificados em virtude da falta de uma terapia eficiente. O objetivo deste trabalho é realizar a síntese total da Licochalcona "A" a partir de um reagente comercial de baixo custo, empregando uma rota sintética de quatro etapas. A síntese inclui uma reação de rearranjo sigmatrópico e a clássica condensação de Claisen-Schmidt, etapas que foram estudadas para encontrar condições reacionais catalíticas apropriadas e de grande viabilidade de execução. Além da licochalcona A, diferentes análogos poderiam ser obtidos. Este trabalho está vinculado à empresa Centagro - Centro Tecnológico Agropecuário Ltda e, portanto, se insere dentro de uma perspectiva de promoção do desenvolvimento científico-tecnológico com vínculos estreitos aos interesses da indústria farmacêutica, da medicina veterinária e do setor produtivo. Realizou-se um estudo detalhado das quatro etapas da rota, testando diferentes condições reacionais. A etapa de reação de prenilação foi realizada empregando diversos substratos para, em seguida, desenvolver um estudo sobre condições reacionais em rearranjos sigmatrópicos-[3,3]. Os produtos das reações de prenilação foram obtidos com sucesso e rendimentos moderados (47- 68%). Na etapa de condensação de Claisen-Schmidt, uma chalcona prenilada desejada foi obtida com sucesso, para a síntese de um análogo da Licochalcona A, mas a etapa final de rearranjo não foi conclusiva. / Licochalcones are naturally present in the root of Glycyrrhiza inflata (licorice) and have many biological activities, such as antitumor, antiparasitic, anti-oxidative and bactericidal. Licochalcone "A" showed anti-leishmania activity, which aroused interest in investigating and testing it for the treatment of canine visceral leishmaniasis (LVC), a serious zoonosis that affects domestic dogs, which are sacrificed due to the lack of an effective therapy. This work aimed to perform the total synthesis of Licochalcone "A" from a low cost commercial reagent using a four step synthetic route. The synthesis includes a sigmatropic rearrangement reaction and the classical Claisen-Schmidt condensation, steps that were studied to find suitable catalytic reaction conditions and viable execution. Besides licochalcone A, different analogues could be obtained. This work is linked to the Centagro - Centro Tecnológico Agropecuário Ltda company and, therefore, falls within a perspective of promoting scientific and technological development with close links to the interests of the pharmaceutical industry, veterinary medicine and the productive sector. A detailed study of the four stages of the route was carried out, testing different reaction conditions. The prenylation reaction step was performed employing several substrates to then develop a study on reaction conditions in sigmatropic rearrangements-[3,3]. The products of the prenylation reactions were obtained with success and moderate yields (47-68%). In the condensation step of Claisen-Schmidt, a desired prenylated chalcone was obtained for the synthesis of an analogue of Licochalcone A, but the final step of rearrangement was not conclusive.

The Systemic Arterial Hypertension (SAH) has a high prevalence and low rates of control and its major complication infarction. In the center of the genesis of these diseases are found the Advanced Glycation Endproducts (AGEs), whose first inhibitor described was the aminoguanidine. Amongst the therapeutic arsenal available for treating hypertension are the guanidines agonists of α2-adrenergic receptors of central action. Given the high prevalence of hypertension and high mortality rates associated with complications of the disease, this work proposes the synthesis of aminoguanidinehydrazones (AGH) with potential application for the treatment of hypertension and at another time, the creation of rigid molecular frameworks for these flexible AGHs that allow the obtention of prototypes that, retaining the anti-hypertensive activity, are useful for prevention of damage caused by ischemic heart disease. It was synthesized 20 AGHs with different aromatic substituents, which yields ranged from about 70 to 90%, using classical methods of condensation between aminoguanidine and different aromatic aldehydes, being described here for the first time the antihypertensive activity for one of them, the compound 234, also known as LQM01. Among the synthesized AGHs, four were selected to serve as the basis for the synthesis of rigid analogs, and 25 different substances were obtained with yields ranging around 40 to 90% using a variety of synthetic strategies. Of these 25 substances, 13 are new, there are no reports in the literature of its synthesis and / or pharmacological activities. In a second step, this paper also proposes a new methodology development study for the reaction of carbon-nitrogen bond formation in aqueous medium catalyzed by copper in order to contribute to the arsenal of currently available reactions for arylation of primary amines and amides, with a reaction that is easy to perform, inexpensive and environmentally friendly. Two new methods were developed, one allowing the arylation of primary amines and other the arylation of primary and secondary amides and certain heterocyclic amines, both supplemented with TPGS using water as solvent and glucose as a reducing agent. In the arylation of primary amines model we bring here 34 examples of reactions, including different aliphatic and aromatic amines and aromatic and heteroaromatic halides with yields ranging around 50 to 90%. We also bring 34 examples of reactions with the catalyst system to arylation of amides, including reactions with aromatic and aliphatic amides, a lactam, aryl and heteroaryl halides, and also some heterocyclic amines with yields ranging around 60 to 90%. This work allowed two important contributions, one in the field of Medicinal Chemistry, with the synthesis of novel derivatives rigid molecular frameworks of AGHs with potential application in cardiovascular disease and other contribution in the field of Synthetic Organic Chemistry, with the development of new methodologies for C-N bond formation in an aqueous medium and with the use of sustainable additives. / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A Hipertensão Arterial Sistêmica (HAS) é uma doença com alta prevalência e baixas taxas de controle, que traz como uma das principais complicações o infarto. No centro da gênese destas doenças encontramos os chamados Produtos Finais de Glicação Avançada (AGEs), cujo primeiro inibidor descrito foi a aminoguanidina. Dentre o arsenal terapêutico disponível para o tratamento da hipertensão estão as guanidinas agonistas de receptores α2‐adrenérgicos de ação central. Tendo em vista a alta prevalência de HAS e taxas de mortalidade associadas às complicações decorrentes da doença, este trabalho propõe a síntese de aminoguanidinoidrazonas (AGHs) com aplicação potencial para o tratamento da HAS e em outro momento, a criação de arcabouços moleculares rígidos para estas AGHs flexíveis que permitam a obtenção de protótipos que, retendo a atividade anti‐hipertensiva, sejam úteis para prevenção dos danos provocados pelas doenças isquêmicas do coração. Foram sintetizadas 20 AGHs carregando diferentes substituintes aromáticos, cujos rendimentos variaram da ordem de 70 a 90%, utilizando metodologia clássica de condensação entre a aminoguanidina e diferentes aldeídos aromáticos, sendo aqui descrita pela primeira vez a atividade anti‐hipertensiva para uma delas, o composto 234, também conhecido por LQM01. Dentre as AGHs sintetizadas, quatro foram selecionadas para servirem como base para a síntese de análogos rígidos, sendo obtidas 25 substâncias diferentes, das classes dos diidroimidazois, tetraidropirimidinas, aminotriazinas, aminopirimidinas e benzotriazepinaminas, com rendimentos variando da ordem de 40 a 90%. Destas 25 substâncias, 13 são inéditas, não havendo relatos na literatura de sua obtenção e/ou atividades farmacológicas Em um segundo momento, o presente trabalho propõe também um estudo de desenvolvimento de metodologia inédita de formação de ligação carbononitrogênio em meio aquoso, catalisada por cobre com o intuito de contribuir para o arsenal de reações disponível atualmente para a arilação de aminas primárias e amidas com uma reação que seja de fácil execução, barata e ambientalmente correta. Foram desenvolvidas duas metodologias inéditas, uma permitindo a arilação de aminas primárias e outra, a arilação de amidas primárias, secundárias e algumas aminas heterocíclicas, ambas utilizando água suplementada com TPGS como solvente e glicose como agente redutor. No modelo de arilação de aminas primárias trazemos aqui 34 exemplos de reações, incluindo diferentes aminas alifáticas e aromáticas e haletos aromáticos e heteroaromáticos, cujos rendimentos variaram da ordem de 50 a 90%. Trazemos também 34 exemplos de reações com o sistema catalítico de arilação de amidas, incluindo reações com amidas aromáticas, alifáticas, uma lactama, haletos de arila e heteroarila e também algumas aminas heterocíclicas, cujos rendimentos variaram da ordem de 60 a 90%. O presente trabalho permitiu duas contribuições importantes, uma no campo da Química Medicinal, com a síntese de inovadores arcabouços moleculares rígidos derivados das AGHs com potencial aplicação em doenças cardiovasculares e outra contribuição no campo da Química Orgânica Sintética, com o desenvolvimento de novas metodologias de formação de ligação C‐N em meio aquoso e com a utilização de aditivos sustentáveis.

O objetivo sintético do presente trabalho é a síntese, caracterização e aplicação do polímero conjugado inédito de baixa Egap, poli(9,9-n-dioctil-2,7-fluorenilenovinilenoalt- 4,7-dibenzotiadiazol-2,5-tiofeno) (PF-BTB). A rota sintética proposta envolve 10 passos, dentre os quais destacam-se reações como a de Wittig e acoplamentos de paládio (Stille e Heck). A caracterização da molécula envolveu as técnicas de RMN de 1H, espectroscopias de infravermelho, UV-VIS e fluorescência, voltametria cíclica, análises térmicas (TGA e DSC) e cromatografia por permeação em gel. A primeira aplicação do polímero se deu na construção de um nariz eletrônico capaz de identificar com ótima precisão três variedades de tabaco (Burley, Flue Cured e Oriental), além de oito diferentes marcas comerciais de cigarro. Esses estudos, além da aplicação prática, serviram para mostrar a eficiência de um tipo novo de sensor para narizes eletrônicos, composto por um mesmo polímero condutor dopado com diferentes porfirinas, denominado sensor híbrido. Por fim, filmes finos do polímero PF-BTB, depositados sobre eletrodos de ouro, tiveram suas propriedades magnetorresistivas testadas em diferentes condições, apresentando valores maiores que 40%, o que é considerado muito alto para esse tipo de fenômeno em filmes poliméricos. / The aim of this work is the synthesis, characterization and application of a novel low Egap conjugated polymer, poly(9,9-n-octyl-2,7-fluorenevinylene-alt-4,7- benzothiadiazole-2,5-thiophene) (PF-BTB). The synthetic pathway comprises 10 steps, involving reaction such as Wittig\'s and palladium cross-couplings (Heck\'s and Stille\'s). The molecule was characterized by the following techniques: 1H NMR, spectroscopic analyses (FTIR, UV-VIS and fluorescence spectroscopy), cyclic voltammetry, thermal analyses (TGA and DSC) and gel permeation chromatography. The polymer was first used to build an electronic nose, which successfully identified three tobacco types (Burley, Flue Cured and Oriental) with high accuracy. The same system could also identify eight different cigarette brands. Besides this practical application, the experiments were designed to show the power of a new sensor type, composed by a single conductive polymer doped with different porphyrins, a composite sensor. Finally, thin films of PF-BTB deposited onto gold electrodes had their magnetoresistive properties tested under different conditions. The material showed magnetoresistance values higher than 40%, which is considered outstanding for this kind of polymeric films.