Estudo das sínteses de orto-quinona-metídeos e orto-diazo-naftoquinonas

• Autor(a) principal: Silva, Milton Neto da
• Data de Publicação: 2003
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal Fluminense (RIUFF)
• Texto Completo: https://app.uff.br/riuff/handle/1/19699
• topic: Beta Lapachona; Ciclodestrinas; Polissacarídeos de Meningitis; Polissacarídeos de de pneumococcos; Ésters quirais; Ácido D-eritronico; Ácido Isoascórbico; Naftoquinonas; Derivados; Síntese orgânica; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA

Several synthetic routes for preparing o-quinone methides were studied. By using an aldolic condensation route with β-lapachone (4a), it was possible to obtain the following o-quinone methides having electron withdrawing group (e.g. carbonyls): 2,2-dimethyl-6-(1-methyl-2-oxo-propylidene)-2,3,4,6-tetrahydro-benzo[H]chromen-5-one (67); 2,2-dimethyl-6-(2-oxo-butylidene)-2,3,4,6-tetrahydro-benzo[H]chromen-5-one (68); 2,2-Dimetil-6-(1-carboxi etil-3-oxo-2-butirideno) 2,3,4,6-tetraidro-benzo [H]cromen-5-ona (69a) e 2,2-Dimetil-6-(1-carboxi etil-3-oxo-4-butirideno) 2,3,4,6-tetraidro-benzo [H]cromen-5-ona (69b).In continuation of these studies, a new regiospecific one-step synthesis of 1-diazo-1H,2H-naphthalen-2-ones, from 1,2-naphthoquinones and p-toluenesulfonylhydrazine in methanol solution at room temperature, was developed. By using this procedures several new substances were prepared: 6-diazo-2,2-dimethyl-2,3,4,6-tetrahydro-benzo[h]chromen-5-one (70); 5-diazo-3-dihydro-2,2-dimethyl-4-oxa-2H,3H-naphthto[1,2-b]furan (71); 1-diazo-2-oxa-1H,2H-naphthalen (73); 1,2-dichloro-3-oxo-4-diazo-3,4-dihydro-naphthalen (75); 1-methoxi-4-diazo-3-oxa-1H,2H-naphthalen (76); 6-diazo-2,2-dimethyl-oxa-2,3,4,6-5-tetrahydro-2H-benzo[h]chromen-3-sulfonic acid (78); 2,2-dimethyl-3-hydroxi-6-diazo-5-oxa-2,3,4,6-tetrahydro-2H-benzo[h]chromen-5-one (80); sodium 4-diazo-3-oxa-1-sulfonate-1H,2H-naphtholate (82). The diazo β-lapachone (70) was tested against Trypanossoma cruzi yielding a value of ED50/24 h = 4961,1 ± 864,3 µm, which compared with crystal violet (ED50, crystal violet/ ED50, de 70 = 0,1) indicated that 70 is inactive. The diazo β-lapachones 70 and 71 were also tested against several type of phatogenic bacteria, but as before they were inactive.The preliminary biological tests with 70 and 71 indicated that the substitution of one of the carbonyl of the o-naphthoquinone moieties by a diazo group reduced the ability of the o-quinones to generate radical oxygen species (ROS) in side the microorganisms tested.