Amines are ubiquitous in nature and serve a variety of functions in living organisms. Because of this fact amines are of great biological and pharmaceutical interest. The iridium catalyst (pentamethylcyclopentadienyl) iridium dichloride dimer ([Cp*IrCl2]2) has been used in a number of ways to synthesize new carbon-nitrogen bonds. These studies were directed toward the development of a method for the iridium catalyzed N-alkylation of alpha-amino acid esters as well as the development of a strategy for synthesis of the natural product 275A. We have optimized a method for the N-alkylation for alpha-amino acid esters. Using this method, we have N-alkylated a series of alpha-amino acid esters with a variety of alcohols. We have shown that the N-alkylation of the alpha-amino acid esters works consistently and gives the desired products in moderate to high yields. We have examined the effect of this method on the chiral center of the obtained products by analyzing their optical rotation. Evaluation of these specific rotations indicated racemization was occurring but it is believed that any loss of the chiral center is due to the reaction conditions. Amphibian alkaloids are of great interest to the pharmaceutical and academic communities due to their biological activities. Unfortunately, they are not naturally available in large quantities which makes total synthesis the most common method of generating these compounds for evaluation. One amphibian alkaloid class of interest to us are the Lehmizidines. These are bicyclic ring structures consisting of a 7-member and 5-member ring with a nitrogen bridgehead. The alkaloid, 275A, was selected as a target for a general synthetic approach. This synthetic approach required the synthesis of novel diols. The construction of these diols along with a method for the synthesis of the azepane ring is presented here.

Orientador: Roberto Rittner Neto / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-16T12:43:04Z (GMT). No. of bitstreams: 1 Martins_CarinaRabelo_D.pdf: 1755898 bytes, checksum: c7a1d0009ba787233a8957afb35ccedb (MD5) Previous issue date: 2009 / Resumo: Este trabalho apresenta estudos teóricos e experimentais sobre estabilidade conformacional de ésteres metílicos de alguns aminoácidos (glicina, alanina, prolina e ácido aspártico) por meio de espectroscopia vibracional e cálculos teóricos da estrutura eletrônica. Os cálculos teóricos foram efetuados com o método ab initio em nível MP2 e com o da Teoria do Funcional de Densidade (¿DFT¿) com diferentes conjuntos de bases e com correção de energia do ponto zero ¿ZPE¿, disponíveis no pacote Gaussian03. Determinaram-se as energias e geometrias dos confôrmeros mais estáveis na fase vapor e com a inclusão dos efeitos do solvente. Os espectros no infravermelho na região do estiramento fundamental do grupo carbonila e no seu primeiro ¿overtone¿, em solventes de diferentes constantes dielétricas, assim como o comportamento dos acoplamentos JHH e JCH em solução foram utilizados para determinar o número e as populações dos rotâmeros presentes. A análise conjunta dos dados permitiu avaliar quais são os fatores responsáveis pela estabilidade conformacional nos ésteres de aminoácidos estudados. No caso do éster do ácido aspártico realizou-se um estudo detalhado RMN de H e C a fim de verificar se os acoplamentos JHH e JCH, dos grupos CH e CH2 apresentavam variação com a mudança da população dos confôrmeros, uma vez que os hidrogênios do grupo CH2 são diastereotópicos, portanto apresentam deslocamentos químicos diferentes e acoplam entre si. Estes dados foram tratados pelo programa Models juntamente com as geometrias previamente otimizadas, o que forneceu informações detalhadas sobre o comportamento conformacional da molécula em solução e também no vapor / Abstract: The present work reports a theoretical and experimental study on the conformational analysis of some amino acid methyl esters (glycine, alanine, proline and acid aspartic) through IR and NMR spectroscopy, and theoretical calculations. The results from ab initio calculations of energy and structure for the main conformers were performed with the Gaussia03 program using MP2 and DFT theory including ZPE corrections and salvation effects. The infra-red spectrum in solvents with wide range of dielectric constants as well the behavior of couplings constants JHH and JCH in solution were used to determine the number and the populations of the rotamers in solution. The analysis of the data allowed the evaluation of the factors responsible for conformacional stability in the studied compounds. For the acid aspartic ester, a detailed investigation was performed using the through Models program, with the optimized geometries from Gaussian combined with experimental couplings constant values, which yielded detailed information on the conformacional behavior of the molecule in solution and also in the vapor / Doutorado / Quimica Organica / Doutor em Ciências