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Orientador: Luiz Carlos Dias / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-10T02:46:17Z (GMT). No. of bitstreams: 1 Fattori_Juliana_M.pdf: 2240885 bytes, checksum: 9db38d985e4bc4fb6668aeb311352757 (MD5) Previous issue date: 2007 / Resumo: A unidade aminodiol está presente em esfingolipídeos que são uma importante classe de biomoléculas. Os esfingolipídeos são componentes das membranas celulares e estão relacionados a processos de crescimento, diferenciação celular e apoptose. Alguns esfingolipídeos como a esfingosina e compostos análogos apresentam atividade antitumoral, por isso metodologias para a obtenção de compostos deste tipo têm despertado a atenção dos químicos orgânicos sintéticos. Assim, neste trabalho foi desenvolvida uma metodologia curta e eficiente para a preparacao de derivados de 2-amino-3,5-diois, com o intuito de fornecer material para testes biologicos. A sintese aqui apresentada envolveu o acoplamento de uma aliltricloroestanana aquiral com a-aminoaldeidos fornecendo alcoois homoalilicos em bons rendimentos e com alta diastereosseletividade. Em seguida a clivagem oxidativa da dupla ligação presente nos álcoois homoalilicos levou a formacao de b-hidroxicetonas inéditas na literatura. E, por fim, a reducao das b-hidroxicetonas sob diferentes condições conduziu aos 2-amino-3,5-diois 1,3-syn e 1,3-anti em bons rendimentos e excelente diastereosseletividade / Abstract: The aminodiol moiety is present in sphingolipids which are an important class of biologically active compounds. These compounds play an important role in the chemistry of cellular membranes, cell growth differentiation and apoptosis. Some of them, like sphingosine and analogues have showed anticancer activity. Therefore procedures to prepare this kind of compounds have been developed by the organic chemists. In this work we have developed a short and efficient route for the synthesis of 2- amino-3,5-diol derivatives, in order to provide material for further biological studies. Our approach to the 2-amino-3,5-diols involved the coupling of an achiral alilthriclorostannane with a-aminoaldehydes to give the corresponding homoallylic alcohols in good yields and with high levels of diastereoslectivity. Double bond oxidation gave the corresponding b-hydroxyketones in excellent yields. Finally, reduction of the b-hydroxyketones under different conditions gave the desired 2- amino-3,5-diols 1,3-syn and 1,3-anti in good yields and high diastereoselectivities / Mestrado / Quimica Organica / Mestre em Química

Orientador: Rogerio Custodio / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-07T11:18:37Z (GMT). No. of bitstreams: 1 Ducati_LucasColucci_M.pdf: 981547 bytes, checksum: 6a6ada0ba07b735cb06198b6cfecf255 (MD5) Previous issue date: 2006 / Resumo: Estudou-se do equilíbrio conformacional da aminoacetona, N,N-dimetilaminoacetona, aminocicloexanona e N,N-dimetilaminocicloexanona por cálculos teóricos e RMN. O equilíbrio conformacional das aminas acíclicas apresentou dois confôrmeros mais estáveis em fase vapor: o sin-periplanar e anticlinal sendo o primeiro mais estável na aminoacetona; ocorrendo a inversão de estabilidade quando troca-se o grupo amino por dimetilamino. A análise populacional de NBO indicou que os confôrmeros são estabilizados por interações de pares de elétrons não-ligantes do oxigênio e/ou nitrogênio com orbitais sigmas antiligantes C-C e C-H, onde sempre as interações se mostraram superiores para o confôrmero com maior grau de simetria. O equilíbrio conformacional das acetonas cíclicas é composto por dois rotâmeros nas orientações sinclinal-axial e sin-periplanar-equatorial, sendo o confôrmero na orientação equatorial mais estável para aminocicloexanona, não ocorrendo inversão da estabilidade com a troca do grupo amino por dimetilamino, resultado reforçado pelas evidências experimentais. A análise populacional de NBO também indicou que as mesmas interações de orbitais presentes nas acetonas acíclicas estabilizam o sistema, sendo também maiores para o confôrmero com maior grau de simetria. Acoplamentos experimentais spin-spin mostraram boa correlação com os acoplamentos calculados, e análises populacionais de infravermelho obtidas de trabalhos anteriores confirmaram a presença dos confôrmeros em solução. / Abstract: The conformational equilibrium of aminoacetone, N,N-dimethylaminoacetone, aminocyclohexanone and N,N-dimethylaminohexanone was studied by theoretical calculations and NMR. The conformational equilibrium of acyclic acetones presents two most stable conformers in the vapor phase: anticlinal and synperiplanar. The second conformer is the most stable for aminoacetone, and the substitution of the amino group by dimethylamino causes the inversion of stability. The NBO populational analysis indicated that the conformers are stabilized by interactions of oxygen and/or nitrogen non-bonding electron pairs with C-C and C-H antibonding sigma orbitals, and these interactions where superior with the conformer of the highest degree of symmetry. The conformational equilibrium of cyclic acetones is made up of two rotamers: synclinal-axial and synperiplanar-equatorial. The equatorial form is the most stable conformer for aminocyclohexanone, and experimental evidences show no stability inversion when the amino group is exchanged with a dimethylamino group. The NBO populational analysis also indicated that the same orbital interactions observed for the acyclic acetones stabilize the system, and are also greater for the conformer with the highest degree of symmetry. Experimental spin-spin couplings showed good correlation with the calculated couplings, and infrared populational analysis obtained from previous works confirmed the presence of conformers in solution. / Mestrado / Quimica Organica / Mestre em Ciências

Screening small molecule libraries is a powerful method for identifying biologically active substances. Current compound libraries are typically comprised of a large number of structurally similar compounds designed around bioactive core structures of known molecules. While the number of tested compounds are increasing, there has been a decline in drug-discovery success due to only a small region of chemical space being represented in these compound libraries. In addition, newly discovered biological targets tend not to be modulated by currently known natural products and molecular scaffolds. Diversity-oriented synthesis (DOS) aims to construct structurally novel and diverse products in a highly efficient manner to generate small-molecule libraries with a high degree of structural diversity and function. There is a need for new organic methodologies to access these atypical molecular scaffolds. The work presented here utilizes photochemical and titanium-mediated methodologies to access novel molecular scaffolds in two distinct directions: 1) by utilizing [2+2] photocycloaddition of pyridone-enynes to access functionalized cyclobutanoids capable of further modification and 2) by developing a novel Bredt’s rule-arrest Kulinkovich-de Meijere reaction to produce alkaloid building blocks with useful functionality. 2-Pyridones are known to undergo photo-initiated [2+2] and [4+4] cycloadditions with themselves and other conjugated -systems. These transformations provide rapid access to highly functionalized cyclobutanoid and cyclooctanoid derivatives capable of further manipulation to access both known and novel chemical space. Utilizing [2+2] photocycloaddition of pyridones conjugated with enyne partners we prepared polycyclic cyclobutanoids with excellent regio- and stereoselectivity. Further, these products were functionalized to give complex tetracyclic molecular scaffolds. The described approach to the 5-8-5 framework of the fusicoccane family features a key intramolecular [4+4] photocycloaddition of tethered pyridones. Intelligent design of the tether and proper choice of solvent affords rapid assembly of the polycyclic framework and sets the relative stereochemistry of five stereogenic centers. The strategy for construction of cyclooctanoid natural products is part of a long standing program to utilize the powerful photochemical properties of 2 pyridone. A novel approach for rapid access to a structurally diverse array of amino-ketone scaffolds employing a Kulinkovich-de Meijere reaction of inexpensive lactam-olefin building blocks has been developed. The formation of cyclopropylamines from alkenes and amides, the Kulinkovich-de Meijere reaction, involves two carbon-carbon bond-forming steps. Strategic use of a tricyclic intermediate can arrest the process if the second step requires formation of a bridgehead double bond. This intramolecular transformation results in formation of carbocyclic amino ketone building blocks. Further manipulation provides access to novel three-dimensional chemical space from these building blocks to produce a spectrum of fused bicyclic scaffolds in a divergent yet predictable manner. These products allow access to complex molecular space that can serve as a platform for medicinal and biochemical investigations. / Chemistry