Reações de Biginelli: uso de ácidos p-sulfônico-calix[n]arenos como catalisadores na síntese de 3,4-diidropirimidinonas de interesse biológico: uso de ácidos p-sulfônico-calix[n]arenos como catalisadores na síntese de 3; 4-diidropirimidinonas de interesse biológico

• Ano de defesa: 2011
• Autor(a) principal: Daniel Leite da Silva
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Reação de Biginelli; Organocatálise; Calixareno; Ressonância magnética nuclear; Síntese orgânica; Química orgânica; Aldeídos; Agentes antineoplásicos; Catalisadores
• Link de acesso: http://hdl.handle.net/1843/SFSA-8FPP9Z

Calix[n]arenes, macrocyclic compounds of phenolic units linked by methylene groups at 2,6-positions, are widely used as ligands for obtaining organometalic catalysts. Their use as organocatalysts is, however, poorly explored. This study focused on the synthesis of six calix[n]arenes and their possible use as organocatalysts in Biginelli reactions. The p-sulfonic acid calix[4]arene (0.5 mol% in ethanol) exhibited the highest catalytic efficiency in 8 h-reaction performed with various aromatic or nonaromatic aldehydes, urea (or thiourea) and ethyl acetoacetate. In Biginelli reaction aromatic aldehydes provided better yields (49-92%) than did non-aromatic ones (31-38%). This approach allowed obtaining 28 dihydropyrimidinones that were further investigated for the antiproliferative activity against human cancer cells and also theability to scavenger 2,2-diphenyl-1-picryhylidrazyl (DPPH) radicals. Adducts AB17 e AB26 presented a broad spectrum of action when used at 10 mg/mL. Compounds AB10 (CI50 = 0.99 g/mL), AB13 (IC50 = 0.25 g/mL), AB26 (IC50 = 0.42 g/mL) were as potent as the reference drug doxorubicin against ovarian (OVCAR-03), drug-resistant ovarian (NCI-ADR/RES) and prostate (PC-3) cancer cells, respectively. For the DPPH- scavenging activity, the adducts AB7, AB8, AB15 and AB16 were the most promising, presenting CS50 values lower than that of the positive control resveratrol (34.4 M). The oxo-adducts (AB7 and AB15) were faster in scavenging DPPH when compared with the corresponding thio-adducts (AB8 and AB16, respectively). Indeed, AB15 was thefastest adduct (527.3 ± 25.7 pmol of DPPH /min) while AB16 was the slowest one (369.8 ± 6.4 pmol of DPPH/min). Overall, an efficient method for obtaining Biginelli adducts was developed based on the use of p-sulfonic acid calix[4]arene as a catalyst. Some of the synthesized adducts were found to be promising for the development of new antitumor and antioxidant agents.