Design, synthesis and biological evaluation of new nitrogen compounds

Author(s)

Marilia Simão dos Santos

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2017-03-14

Examining board members

Fernando Antonio Santos Coelho; Ivone Carvalho; Kleber Thiago de Oliveira; Luciana Gonzaga de Oliveira; Airton Gonçalves Salles Junior

• Advisor: Fernando Antonio Santos Coelho

Abstract

Nitrogenated organic compounds play a very relevant role in both chemistry and biology, being employed as catalysts, bases and ligands, as well as medicines, constituents and products of biological systems. The interest in such structures was explored in the designing and synthesis of molecules with antifungal activity, N-substituted imidazolic derivatives and highly substituted aza-?-lactams. The incidence of fungal infections has drastically increased through the years due to the growth of immunocompromised individuals associated to the limited supply and efficacy of the available drugs. Based on the structure of azole drugs, and in models of structure-activity relationship present in the literature, two novel hybrids were designed and synthesized. The hybrids synthesized presented an antifungal activity, allowing the validation of the developed proposal. Substituted N-imidazolic derivatives were synthesized directly from Morita-Baylis-Hillman (MBH) adducts. The in situ activation of the MBH adduct was performed employing 1,1¿-carbonyldiimidazole (CDI) in the presence of imidazole in acetonitrile. The compounds were obtained with yields ranging from good to excellent (68-95%) and high stereoselectivity in favour of the E-isomer. The synthesis of the aza-?-lactams was based on the intramolecular N-H insertion of a diazo intermediate in the presence of rhodium acetate dimer. The four-membered heterocycles with a varied substitution pattern were obtained in a sequence of 5 to 9 steps allowing the generation of library of new compounds for biological screening (AU)

• FAPESP's process: 12/08048-0 - Morita-Baylis-Hillman in medicinal chemistry: design, synthesis and biological evaluation of potential antifungal agents
• Grantee: Marília Simão dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate