Síntese e estudo conformacional de algumas arilamidas derivadas de ésteres de l-cisteína, potenciais inibidores de HIV-1 protease

• Ano de defesa: 2016
• Autor(a) principal: Espirito Santo, Stephanie Amarillis do [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: AIDS; Arylamides; S-nitrosothiols; Coupling reagents; Conformational analysis; Arilamidas; S-nitrosotióis; Reagentes de acoplamento; Análise conformacional
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3755328; http://repositorio.unifesp.br/handle/11600/46191

AIDS is a disease that challenges public health on a global scale and which results in major problems due to its side effects, once patients submitted to antiretroviral therapies are bound to develop hypertension. In this context, this project aimed to synthesize new arylamides with structural similarity to the commercial antiretroviral Nelfinavir, which in further S-nitrosylation reaction studies, has potential to provide dual inhibition to HIV-1-PR and renin, vital compounds to the evolution of AIDS andhypertensionrespectively. The arylamides of interest were prepared by the coupling of substituted benzoic acids and L-cysteine derivatives via the coupling reagents DCC and COMU underclassical methods and assisted by microwaves, aiming the analysis of the reaction energy efficiency, in two different solvents (dichloromethane and dimethylcarbonate), in order to evaluate the replacement of a polluting solvent by a green one. The results of the coupling reactions showed that the solvent dichloromethane and the classical method proved to be efficient in termsof yield, although the solvent dimethylcarbonate and the methodology assisted by microwaves showed to have competitive performance and in fact might be used as a potential alternative route due to its environmentally friendly approach (green solvent and energy efficiency).Finally, it can be concluded that both coupling reagents COMU and DCC had similar average yield sand the arylamides of interest could be prepared efficiently by both reagents, either in dichloromethane or in dimethylcarbonate, usingirradiation and even classical methodologies. The theoretical calculations performed for the arylamides under study showed two stableand low-energy conformations, regardless ofthesubstituent, being the gauche conformation the most stable and with a contribution of population of approximately 60%, and the cis coformation with a populationof 40 %. The forces responsible for the stability of the gauche conformation are the electronic interactions which provides stability through intramolecular hydrogenbonds, and the Repulsive Field Effect which contributes to the hyperconjugative interactions between the p anti bonding orbital of the C = O Bond and the s bonding orbital of the C-Y bond.