Abstract: Mitomycins and its analogs have been widely used for treating various tumors. In order to obtain excellent yield and environmental friendliness, an efficient one-pot process for the synthesis of 2-(butylamino)-3-methyl-1, 4-benzoquinone (c), a mitomycin-like compound by the domino reaction of 2-methylbenzene-1, 4-diol and butylamine using laccase/lipase as co-catalysts, has been developed. In the work, the process proposed here was improved by optimizing the relevant factors using the response surface methodology. The optimum conditions were obtained as follows: molar ratio of 2-methylbenzene-1, 4-diol to amine was 1.16∶1, activity ratio of laccase to lipase was 1.14∶2 and reaction temperature was 38.9 ℃, in which the highest yield was 87.17%. The yield model was established, which considered the effects of the amount of 2-methylbenzene-1, 4-diol to amine, the activity ratio of laccase to lipase and the reaction temperature on the yield and could accurately predict the yield (R=0.994 1). The results obtained indicate that this process may be useful as a green alternative process forhigher yield production of mitomycin analogs.

Key words: lipase, response surface methodology, laccase, mitomycin-like compound