Síntese de lapachonas 1,2,3-triazólicas em um único vaso de reação

Este trabalho descreve a síntese de 11 análogos inéditos da lapachona com modificação no anel furânico pela inserção de um núcleo 1,2,3-triazólico. Utilizou-se a 2-(azido-metil)-2,3-dihidronafto[1,2-b]furan-4,5-diona (46) com diferentes tipos de alcinos comerciais para formação dos produtos finais, nor-β-lapachonas 1-H-1,2,3-triazolicas (40a-k). Inicialmente apresentou-se uma metodologia de 4 etapas para síntese do 2-((4-propil-1-H-1,2,3-triazol-1-il)metil)-2,3-dihidronafto[1,2-b]furan-4,5-diona (40a), porém mostrou-se possível uma síntese em único vaso de reação, que possibilitou a economia de 3 das 4 etapas reacionais. O mesmo composto foi sintetizado pela segunda metodologia observando-se rendimentos próximos, mas a one-pot mostra-se muito mais eficiente por ser considerada uma química verde, devido a economia de solventes e reagentes, já que não possui 2 etapas de extração e purificação. Sendo assim, esta metodologia foi a empregada na síntese dos outros 10 compostos, sendo todos os 11 inéditos. A maioria das moléculas foram caracterizadas por ressonância magnética nuclear de 1H, 13C/APT e infravermelho e foram enviadas para testar suas possíveis atividades anticancerígenas na USPThis work describes an analogous synthesis of lapachone with its furan ring modified by the insertion of a 1,2,3-triazole nucleus. It was used 2-(azido methyl) -2,3-dihidronaphtho[1,2-b]furan-4,5-dione (46) with 11 types of commercial alkynes to produce the final product, nor-β -lapachonas 1-H-1,2,3-triazolys (40a-k). Initially, it is presented a 4-steps method for the synthesis of 2-((4-propyl-1 H-1,2,3-triazol-1-yl)methyl)-2,3-dihidronaphtho[1,2-b]furan-4,5-dione (40a). Neverthless, it was observed to be possible a synthesis in one single reaction vessel, which enabled skipping 3 of the 4 reaction steps. The same compound was synthesized using the second methodology observing similar yields. The one-pot appears to be much more efficient for being considered a green chemistry, since it reduced the use of solvents and reagents, as it has no 2 steps extraction and purification. Thus, the latter method was employed in the synthesis of other 10 compounds, totalizing 11 unpublished molecules. Most molecules were characterized by 1 H, 13 C/APT nuclear magnetic resonance and infrared spectroscopy. Also, they were evaluated to anti-cancer activity at US

Synthesis and Cytotoxic Evaluation of 1H-1,2,3-Triazol-1-ylmethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones

ABSTRACT The 1,2-naphthoquinone compound was previously considered active against solid tumors. Moreover, glycosidase inhibitors such as 1,2,3-1H triazoles has been pointed out as efficient compounds in anticancer activity studies. Thus, a series of eleven 1,2-naphthoquinones tethered in C2 to 1,2,3-1H-triazoles 9a-k were designed, synthesized and their cytotoxic activity evaluated using HCT-116 (colon adenocarcinoma), MCF-7 (breast adenocarcinoma) and RPE (human nontumor cell line from retinal epithelium). The chemical synthesis was performed from C-3 allylation of lawsone followed by iodocyclization with subsequent nucleophilic displacement with sodium azide and, finally, the 1,3-dipolar cycloaddition catalyzed by Cu(I) with terminal alkynes led to the formation of 1H-1,2,3-Triazol-1-ylmethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones in good yields. Compounds containing aromatic group linked to 1,2,3-triazole ring (9c, 9d, 9e, 9i) presented superior cytotoxic activity against cancer cell lines with IC50 in the range of 0.74 to 4.4 µM indicating that the presence of aromatic rings substituents in the 1,2,3-1H-triazole moiety is probably responsible for the improved cytotoxic activity