Síntese De 2-(2-Piridil)quinolinas Promovida Por Micro-Ondas E Suas Atividades Antifúngicas

Abstract

publicado na web em 12/09/2017 SYNTHESIS OF 2-(2-PYRIDYL)QUINOLINES PROMOTED BY MICROWAVES AND THEIR ANTIFUNGAL ACTIVITIES.In this work a series of 2-(2-pyridyl)quinolines were prepared via a Povarov reaction between anilines, 2-pyridinocarbadehyde and ethyl vinyl ether under microwaves heating conditions. The optimized conditions herein reported allowed the preparation of several pyridylquinolines in yields in the range of 30-83%, some of them not previously accessible by this multicomponent process. The reported methodology has advantage over previous report due to its larger scope and short reaction time (2 hours). All quinolines obtained were assayed against five species of clinically important yeasts Candida sp and against Cryptococcus neoformans. Some of them possessed a broad spectrum of action including 2-(2-pyridyl)quinoline (20) and 6,8-dimethoxy-2-(pyridin-2-yl)quinolone (22) that were highly effective in inhibiting Candida species (IC 50 < 1.95 µg/mL against C. tropicalis and C. krusei). Some compounds were more potent than commercial drugs Nistatin and Miconazole.Keywords: microwave; Povarov multicomponent reactions; pyridylquinoline; antifungal activity. Figura 1. Estruturas de quinolinas bioativas naturais 1-2 e sintéticas 3-8.

The Povarov Reaction: A Versatile Method to Synthesize Tetrahydroquinolines, Quinolines and Julolidines

“…1,8 When no oxidizing agent is added to the reaction medium, O 2 (air) is the final oxidant. 14,136 Similarly to the synthesis of THQs, these reactions can be catalyzed by Lewis and Brønsted acids such as BF 3 •OEt 2 , 36,40,137-142 BF 3 •O(CH 3 ) 2 , 143,144 FeCl 3 , 145,146 InCl 3 , 147 trifluoromethanesulfonic acid, 148 p-toluenesulfonic acid, 146 CX4SO 3 H, 14,149 TFA, 150,151 camphorsulfonic acid, 152 tris(4-bromophenyl)aminium (TBPA + ), 140,[153][154][155] CBr 4 , 156 iron, 157 copper iodide 158 and iodine. [159][160][161][162][163][164][165][166][167] Furthermore, different triflates have been widely used such as Sc(OTf) 3 , 154,168,169 Yb(OTf) 3 , [170][171][172][173] Cu(OTf) 2 , 174,175 Ce(OTf) 3 , 176,177 Zn(OTf) 2 , 178 AgOTf, 22 In(OTf) 3 179 and Ca(OTf) 2 .…”

Inibição Do Crescimento De Microrganismos Patogênicos Induzida Por Butenolídeos Análogos Aos Cadiolídeos

“…RMN de 1 H (300 MHz, CDCl 3 ) δ 3,84 (s, 3H, 7'), 3,88 (s, 3H, 7''), 6,92 (d, J 3',2' = J 5',6' = 8,4 Hz, 2H, 3' e 5'), 6,97 (d, J 3'',2'' = J 5'',6'' = 8,5 Hz, 2H, 3'' e 5''), 7,62 (d, J 2',3' = J 6',5' = 8,4 Hz, 2H, 2' e 6'), 8,18 (d, J 2'',3'' = J 6'',5'' = 8,5 Hz, 2H, 2'' e 6''). RMN de 13 C (75 MHz, CDCl 3 ) δ 55,5 (7'), 55,6 (7''), 86,8 (2), 93,5 (1), 112,1 (1'), 113,8 (3'' e 5''), 114,4 (3' e 5'), 130,4 (1''), 131,9 (2'' e 6''), 135,0 (2' e 6'), 161,5 (4'), 164,3 (4''), 176,8 (3) 14), 239 (12), 238 (71), 224 (16), 223 (100), 195 (28), 180 (12), 163 (7), 160 (7), 159 (71), 152 (29), 151 (10), 144 (18), 135 (20), 131 (6), 126 (7), 119 (35), 116 (23), 107 (7), 92 (24), 88 (21), 87 (8), 77 (43), 76 (11), 75 (13), 74 (11), 64 (24), 63 (36), 62 (23), 51 (15), 50 (14).…”

“…Os seguintes experimentos-controle foram realizados conforme descrito por Borel et al: 29 (i) controle de crescimento dos microrganismos, visando avaliar a viabilidade celular; (ii) branco, solução sem o inóculo do microrganismo, com finalidade de eliminar o efeito da coloração da solução das substâncias teste; (iii) controle positivo, no qual as substâncias teste foram substituídas pelo antifúngico Miconazol ou pelo antibiótico Ampicilina; (iv) controle do grau de esterilidade do meio de cultura, contendo 100 µL de meio de cultura e 100 µL de água destilada.…”