Síntese de análogos conformacionalmente livres do 11-tosil-6,6a,11,11a-tetraidro-5H-benzo[a]carbazol

• Autor(a) principal: Faria, Luiz Antonio Moreira de
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UERJ
• Texto Completo: http://www.bdtd.uerj.br/handle/1/15848
• topic: Sulfonamides; carbaisoflavanones; reductive amination; Sulfonamidas; carbaisoflavanonas; aminação redutiva; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA

In this work it is proposed the preparation of six analogues of 11-tosyl-6,6a,11,11a-tetrahy-5H-benzo[a]carbazole (LQB223), an aza-pterocarpan with antiproliferative action on tumor cells (leukemia and colon) and antiparasitic (Tripanossoma cruzi and Plasmodium falciparum). The target molecules were divided in three groups, prepared from the sulfonamidation reaction of key intermediates 1-amino-1-aryl-tetralin, N-aryl-1-amino-tetralin and 1-amino-tetralin (Groups 1,2 and 3, respectively), all of them derived from tetralones commercially available (α-tetralone and 6-metoxi-α-tetralone). It is worth to mention only two among the six proposed targets are known and none of them were pharmacologicaly evaluated. The products of reductive amination of tetralones and α-arylated tetralone have already been obtained in good yields (~85%). These products were obtained by reacting tetralones with ammonium acetate and sodium cyanoborohydride, under heating in sealed tube during 16 hours. The reductive amination of tetralone with aniline in the presence of sodium borohydride and activated with boric acid failed. A new strategy for the synthesis of phenylimine from tetralone and aniline has been adopted by using p-toluenesulphonic acid as the catalyst in a Dean Stark trap and further reduction. The use of sodium borohydride showed to be not effective for the reduction of the imine. It was also tested an alternative with copper II catalyzed Buchwald´s amination between 1-amino-tetralin and phenylboronic acid. The product was observed but in a mixture with other compounds. The sulfonamidation of amino-tetralins was achieved under two conditions CuO catalysis with tosyl chloride, at room temperature or through ball milling of amino-tetralin and tosyl chloride in the presence of K2CO3. The sulfonamides were obtained in moderate yields, without optimization