Microwave Assisted Synthesis of Phenazines from β-Lapachones and Their Tuberculostatic Activity

Aims: The study aimed to investigate de synthesis of phenazines by microwave assisted reactions and evaluate the tuberculostatic activity.

Study Design: The method developed in the study is an alternative for the method described in the literature employing acetic acid, an efficient solvent for the reaction, but corrosive and aggressive health. In addition tuberculostatic activities of phenazines were assessed and a brief study on molecular modeling of the phenazines was performed.

Place and Duration of Study: The experiments were performed on Instituto Federal do Rio de Janeiro (IFRJ), Fundação Oswaldo Cruz (FIOCRUZ) and Núcleo de Pesquisas em Ecologia e Desenvolvimento Social de Macaé (NUPEM) between 2012-2015.

Methodology: Quinone (1 mmol) and 5 mmols of o-phenylenediamine were dissolved in 10 ml of 1,4-dioxane in a sealed tube. Microwave reactor conditions were: temperature 150°C and 4.5 bar pressure for 15 minutes. After the reaction water was added to the reaction media and the yellow precipitate formed was filtered under vacuum and washed 3 times with water. The phenazine was purified by silica gel column chromatography using a mixture of hexane-ethyl acetate 95 : 5 as eluent, the phenazine were obtained in yields greater than 85% in all cases.

Results: Six phenazines derived from β-lapachonas were synthesized by microwave assisted reactions with good yields. The tuberculostatic activity of the five phenazines was significantly lower than phenazine from β-lapachone, a brief molecular-modeling study performed showed that the higher activity of phenazine from β-lapachone is due its polarity (µ) and Polar Surface Area (PSA).

Conclusion: The microwave irradiation was effective to synthesize phenazines from β-lapachones faster and with similar yields.