Reações entre (e)-5-bromo-1,1,1-trialo-4-metoxipent-3-en-2-onas e aminoácidos para produção de heterociclos de 5, 6 e 7 membros

Abstract

This work present the versatility of 4-alkoxy-5-bromo-1,1,1-trialopent-3-en-2-ones in reactions with amino acids, exploring the four reactive centers of this building block and leading to the formation of heterocycles of 5, 6 and 7 members. Initially, a regioselective protocol was developed, using α-amino acids free of protecting groups, in one-pot reactions to obtain enantiomerically pure morpholin-2-ones. The reaction was selective for the formation of the Z regioisomer in all cases, however when a secondary amino group was used, only the E isomer was observed. The synthesized compounds were obtained in up to 92% yields. In the second step, the protocol previously developed was treated with β-amino acids derived from 4 and 5 substituted 2-aminobenzoic acids affording the corresponding of 7-membered heterocycles, benzoxazepinones, with up to 86% yields. These series of compounds showed solid state fluorescence and studies were carried out on their photophysical properties and their interaction with CT-DNA and BSA. In the third stage of the work, a series of 5-bromo enamino esters were synthesized, wich where used as intermediate for the synthesis of 3 differents heterocycles; in this regard, a séries of reaction parameters were evaluated incluiding, solvent, temperature and base. For instance using inorganic bases it was possible to synthesize furans with up to 85% yield. With primary amines, a selective reaction pathway was obtained for the formation of pyrroles with up to 93% yield, and piperazin-2-ones with 91% yield. The heterocycles developed in this work have structures similar to compounds with biological activity, making it interesting to study their properties. The structures of the compounds were elucidated by 1H, 13C NMR experiments, 2D NMR analyzes as well as X-ray experiments.