£^-Substituted £\,£]-unsaturated £_-lactams was synthesized from £\-sulfinyl acetamides in three steps. Formal synthesis of (¡Ó)-Protoemetinol was also reported.

A formal [3+3] cycloaddition strategy to substituted glutarimides was studied. N-Alkyl-sulfonylacetamides and various a,b-unsaturated esters were used as starting materials. Regioselective reduction of N-alkyl-3-sulfonyl glutarimides and the applications in pharmaceuticals and natural product synthesis

We report the development of a general route to the synthesis of [4.3.1], [3.3.1], an especially [3.2.1] bicyclic compounds structurally related to vitisinol D, a natural product. This allows for diastereoselective synthesis of bicyclic compounds with five adjacent chiral centers. This route was employed in a preliminary SAR investigation into the neuroprotectant effect of small molecules in an in vivo experiment measuring the degree of restorative effect of synaptic transmission in the neuromuscular junction of Drosophila melanogaster larvae under acute oxidative stress. One of the compounds exhibited intriguing potential as a neuroprotectant and outperformed resveratrol in restoring synaptic function under oxidative stress. The hypothesis that bridged bicyclic compounds may hold promise as drug scaffolds due to their conformational rigidity and ability to orient functional appendages in unique orientations is developed. The second focus is a mechanistic investigation into a tetrabutylammoniumcatalyzed cycloaddition as evidence of a novel ammonium-alkyne interaction. A carbamate nitrogen adds to a non-conjugated carbon–carbon triple bond under the action of an ammonium catalyst leading to a cyclic product. Studies in homogeneous systems suggest that the ammonium agent facilitates cyclitive nitrogen–carbon bond formation through a cation–π interaction with the alkyne unit. Using Raman spectroscopy, this cation–π interaction is directly observed for the first time. DFT modeling elucidated the mechanistic factors in this cycloaddition. A teaching experiment was developed based on this mechanistic investigation. Control experiments were employed to demonstrate the testing of two alternative mechanistic hypotheses. Cyclization reactions were performed with a soluble base (sodium phenoxide) with and without tetrabutylammonium bromide under homogeneous conditions. Students observed that ammonium salt accelerates the reaction. They were encouraged to develop a testable hypothesis for the role of the ammonium salt in the cyclization mechanism: typical phase transfer or other. IR spectroscopy was used to directly observe a dose dependent shift of the alkyne stretching mode due to a cation−π interaction. Undergraduates were able to employ the scientific method on a contemporary system and see how data are generated and interpreted to adjudicate between rival hypotheses in a way that emulates authentic and current research in a lab setting. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

京都大学 / 0048 / 新制・課程博士 / 博士(工学) / 甲第18950号 / 工博第3992号 / 新制||工||1615(附属図書館) / 31901 / 京都大学大学院工学研究科材料化学専攻 / (主査)教授 松原 誠二郎, 教授 辻 康之, 教授 中尾 佳亮 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

The present thesis will be largely focused on identifying and understanding the scope and mechanistic details associated with the tetrabutylammonium fluoride (TBAF) mediated cyclization of alkynyl hydrazines and (O)-hydroxylamines. Also, the synthesis of 2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid (CMPF) and its analogs will be discussed along with an analysis of their effects on insulin secretion. Chapter 1 will present the importance of developing isoxazoline and pyrazoline type heterocycles given that they are continually demonstrated to possess a variety of biological activities. Further, the scope of the reaction in terms of functional group tolerability, scalability and mild conditions will be shown. To expand the importance of this work, a route to access non-racemic heterocycles is also noted. With the heterocycles in hand, new methods were developed to generate more complex frameworks in the form of a novel one pot deprotection/functionalization reaction. Chapter 2 will focus on mechanistic investigations of the cyclization. From the initial discovery of the reaction, its actual mechanism was unknown and a main point of interest. What appeared unusual is that a nucleophilic attack occurs on an unactivated triple bond. Given the identity of the products, a reasonable proposal was a 5-endo-dig type cyclization. However, such a pathway would result in the generation of a vinyl anion intermediate which is well known to be of very high energy and it would seem unlikely to occur under mild conditions. Various trapping experiments were used to demonstrate that the vinyl anion forms and a 5-endo-dig-cyclization is the operative mechanism. Chapter 3 analyzes the importance of the tetrabutylammonium fluoride reagent. During optimization studies, it became clear that this base is the ideal reagent to facilitate the cyclization although other bases can also enable the transformation at much slower rates. Addition of non-basic ammonium salt additives to bases such as KF and CsF had a dramatic effect on the rate of the reaction. To determine whether the observed rate differences were merely a phase transfer effect or something more, both empirical and Raman spectroscopy data were collected. Based on this, the first evidence for an ammonium-alkyne cation-pi type interaction was shown. Chapter 4 will summarize the work on the synthesis of 2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid (CMPF) and its analogs in order to be used in various biological assays. The main goals were to determine a possible structure activity relationship between the substrates and insulin secretion in beta cells and also determine the fate of CMPF in vivo. Several 13C labeled analogs of CMPF were synthesized and successfully used to show for the first time that CMPF in metabolized in vivo in mice. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2017. / FAU Electronic Theses and Dissertations Collection

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-15T15:40:19Z No. of bitstreams: 1 Wilson Silva do Nascimento.pdf: 1102619 bytes, checksum: f3fd4580e9425c165601806a91092eda (MD5) / Made available in DSpace on 2017-02-15T15:40:19Z (GMT). No. of bitstreams: 1 Wilson Silva do Nascimento.pdf: 1102619 bytes, checksum: f3fd4580e9425c165601806a91092eda (MD5) Previous issue date: 2011-02-15 / In the present study was performed the synthesis of a new series of 1,2,3- triazole derivative 1,4-disubstituted naphthoquinone group containing the position of a heterocyclic ring from the reaction of 1,3-dipolar cycloaddition between the two precursor azido-1,4-naphthoquinone and 10 terminal alkynes, using a method that employs the use of CuI as the catalytic species for the regioselective formation of the triazole and acetonitrile as solvent. Other methods were also tested, including the one described by using Sharpless reducing environment, however, these methods were less effective or not promoted the formation of the triazole ring. Two of these triazoles had obtained the hydroxyl groups present in its structure acetylated methodology developed in our laboratory using acetic anhydride and montmorillonite K-10 by ultrasound, a total number of 12 new structures of [1,2,3]-triazole 1,4- disubstituted. A second route to obtain 1,4-disubstituted triazoles connected to 1,4- naphthoquinone was proposed from the reaction between 2-ethynyl-1,4- naphthoquinone and azido compound, for it was synthesized the 2-(3-hydroxy-3- metilbutinil)-1,4-naphthoquinone. However, the subsequent reaction of deprotection of this compound, as well as the synthesis of the precursor 2-trimethylsilyl-1,4- naphthoquinone did not work. All the products of unknown structures were characterized by 1H NMR and 13C NMR, elemental analysis, LC-MS and infrared. / No presente trabalho foi realizada a síntese de uma nova série de derivados 1,2,3-triazólicos 1,4-dissubstituídos contendo o grupo naftoquinona na posição 1 deste anel heterocíclico a partir da reação de cicloadição 1,3-dipolar entre o precursor 2-azido-1,4-naftoquinona e 10 alcinos terminais, utilizando um método que emprega o uso de CuI como espécie catalítica para a formação regiosseletiva do anel triazólico e acetonitrila como solvente. Outros métodos também foram testados, entre eles o descrito por Sharpless que utiliza meio redutor, no entanto, estes métodos mostraram-se menos eficiente ou não promoveram a formação do anel triazólico. Dois destes triazóis obtidos tiveram os grupos hidroxilas presente em sua estrutura acetilados por metodologia desenvolvida em nosso laboratório utilizando anidrido acético e montmorillonite K-10 em ultra som, totalizando uma série de 12 novas estruturas de [1,2,3]-triazóis 1,4-dissubstituídos. Uma segunda rota para a obtenção dos derivados triazólicos 1,4-dissubstituídos ligados à 1,4- naftoquinona foi proposta a partir da reação entre o 2-etinil-1,4-naftoquinona e azido composto, para isso, foi sintetizado o 2-(3-hidroxi-3metilbutinil)-1,4-naftoquinona. No entanto, a subseqüente reação de desproteção deste composto, assim como, a síntese do precursor 2-trimetilsilil-1,4-naftoquinona não funcionou. Todos os produtos obtidos de estruturas inéditas foram caracterizados por espectroscopia de RMN 1H e RMN 13C, análise elementar, LC-MS e infravermelho.

Acyl phosphonates are interesting precursors for the synthesis of biologically active compounds. In the first part, the acyl phosphonates are synthesized starting from the corresponding acyl chloride. The acyl chlorides are converted into acyl phosphonates by using trialkylphosphites. The reaction of acyl phosphonates with aldehydes in the presence of proline furnished not the suggested aldol products via proline catalyzed aldol reaction but bicyclic products via one pot tricomponent 1,3-dipolar cycloaddition reaction. The formation of the bicyclic compound was suggested as followed / The formation of iminium salt of proline with aldehyde followed by decarboxylation furnished azomethine. The 1,3-dipolar cycloaddition of the formed azomethine with carbonyl group of acyl phosphonate afforded substituted hexahydro pyrrolo oxazole structures. 1,3-Dipolar cycloaddition forms the basis of the most preparatively useful procedures for the synthesis of five-membered heterocycles. One example is the 1,3-dipolar cycloaddition of azomethine ylides (from imines) and alkenes, which allows the stereoselective synthesis of pyrrolidines or proline derivatives.

Submitted by Irene Nascimento (irene.kessia@ufpe.br) on 2017-07-14T19:24:36Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação lucas pereira 20.01.16 14h.pdf: 3030489 bytes, checksum: d08690f65be6ab72afc4f01820c878d4 (MD5) / Made available in DSpace on 2017-07-14T19:24:36Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação lucas pereira 20.01.16 14h.pdf: 3030489 bytes, checksum: d08690f65be6ab72afc4f01820c878d4 (MD5) Previous issue date: 2014-08-03 / Capes / Em estudos prévios, realizados por Almeida, foram obtidas substâncias 2-isoxazolinas aza-biciclicas, que deram origem a núcleos como o 2-isoxazolina[5,4-b]piperidina e 2- isoxazolina[5,4-b]pirrolidina. Amidas N benzoiladas derivadas dessas substâncias apresentaram-se farmacologicamente ativas, principalmente em testes anti-inflamatório e antimicrobianos realizados com esses compostos. Além disso, várias substâncias contendo a função oxima, em sua forma livre e como éteres de oxima, são descritas na literatura, apresentando atividades biológicas antimicrobianas. Diante disso, foi obtido através da hibridização molecular, derivados 2-isoxazolínicos aza-biciclico contendo a função oxima em sua estrutura. Os ésteres isoxazolínicos 34 e 36 foram obtidos através de reações de cicloadição 1,3-dipolar por duas diferentes rotas sintéticas, pela reação do óxido de nitrila 41 (CEFNO) tanto com o enecarbamato cbz, quanto com as enamidas endocíclicas para-substituídas. Os cicloadutos oriundos do enecarbamato endocíclico, sofreram reações de hidrogenólise e posterior N-benzoilação. A porção éster, presente nos compostos N-benzoilados para-substituídos, foi reduzida a álcool e em seguida submetida a uma oxidação de Swern, resultando nos aldeídos isoxazolínicos. A partir desses aldeídos 38, através de uma reação com hidroxilamina, chegou-se nas oximas isoxazolínicas 39. Os novos derivados foram submetidos a testes biológicos com o intuito de avaliar sua atividade antimicrobiana. O teste foi realizado pelo método de difusão em disco, contendo bactérias Gram negativas e Gram positivas, onde os derivados isoxzolínicos apresentaram halos variados frente aos microrganismos em estudo. O composto 39b caracterizou-se como uma substância promissora no desenvolvimento de novos agentes antimicrobianos, com halos de 10 mm para o Staphylococcus aureus, 11 mm para o Micrococcus luteus, 13 mm Bacillus subtilis e 13 mm para o microrganismo Micobacterium smegmatis. / In previous studies conducted by Almeida substances were obtained isoxazolines 2-azabicyclic, giving rise to nuclei as 2-isoxazoline [5,4-b] piperidine and 2-isoxazoline [5,4-b] pyrrolidine. N benzoiladas amides derived from these substances had become pharmacologically active, especially in anti-inflammatory and antimicrobial tests conducted with these compounds. Furthermore, substances containing various oxime function, in free form and as oxime ethers are described in literature, showing microbial biological activities. Thus, was obtained by molecular hybridization, derivatives aza-bicyclic 2-isoxazolínicos containing the oxime function in its structure. Esters isoxazolínicos 34 and 36 were obtained by cycloaddition 1,3-dipolar cycloaddition reactions of two different synthetic routes, by reaction of the nitrile oxide 41 (CEFNO) with both the cbz enecarbamate, as with the endocyclic enamides para-substituted. Cicloadutos coming from the endocyclic enecarbamate suffered reactions of hydrogenolysis and subsequent N-benzoylation. The ester moiety present in the N-substituted compounds for benzoilados was reduced to alcohol, and then subjected to a Swern oxidation, resulting in isoxazolínicos aldehydes. From these aldehydes 38 by means of a reaction with hydroxylamine, was reached in isoxazolínicas oximes 39. The novel derivatives were subjected to biological tests in order to evaluate its antimicrobial activity. The test was performed using the disk diffusion method, comprising Gram negative and Gram positive where isoxzolínicos halo derivatives showed varied across the microorganisms under study. Compound 39b was characterized as a promising substance in the development of new antimicrobial agents with halos of 10 mm for Staphylococcus aureus, 11 to Micrococcus luteus mm, 13 mm and 13 mm Bacillus subtilis microorganism Mycobacterium smegmatis for.

β-lactam antibiotics have been the most widely used drug of choice to combat infectious disease caused by bacteria. Unfortunately, their effectiveness is drastically threatened by bacterial β-lactamases. β-lactamases is responsible for the resistance to most antibiotic drugs. For decades, β-lactam β-lactamases inhibitors have been used to reduce bacterial resistance; however, in this study 1,2,4-oxadiazolidinone derivatives as a non-β-lactam β-lactamases inhibitor against TEM-1 and P99 β-lactamases. The significance of oxadiazolidinone is the prominent five-membered ring scaffold in its structure, which is configurationally stable and present in other biologically active compounds such as linezolid and avibactam. Oxadiazolidinones were synthesized by treating nitrones with isocyanates. The synthesized compounds were characterized using 1H and 13C NMR, GC-MS, and FTIR. Afterward, they were tested using Nitrocefin as substrate to determine their effectiveness against TEM-1 and P99 serine β-lactamase. Compound 2a-2c, and 3 showed inhibition ranging from 12-38%.

Orientador: Carlos Roque Duarte Correia / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-05T22:30:16Z (GMT). No. of bitstreams: 1 Burtoloso_AntonioCarlosBender_D.pdf: 10110814 bytes, checksum: 1e36973f12232933308e658cdad952fe (MD5) Previous issue date: 2006 / Doutorado / Quimica Organica / Doutor em Ciências