漆酶/脂肪酶催化制备丝裂霉素类似物及其响应面法优化

丝裂霉素及其类似物,广泛应用于各种肿瘤.为了获得优异的产率和环境友好性,采用一锅法工艺,以漆酶/脂肪酶为催化剂,催化2-甲基苯-1,4-二酚与正丁胺的多米诺反应制备丝裂霉素类似物2-丁胺-3-甲基-1,4-苯醌(c).采用响应面技术优化了反应条件:2-甲基苯-1,4-二酚与胺的物质的量比为1.16∶1、漆酶与脂肪酶的活性比为1.14∶2、反应温度为38.9 ℃,最佳产率达到87.17%.建立了产率模型,该模型考虑了2-甲基苯-1,4-二酚与胺的物质的量比、漆酶与脂肪酶活性比和反应温度对产率的影响,可以准确的预测产率(R²为0.994 1).漆酶/脂肪酶协同催化体系一锅法合成丝裂霉素类似物,显著提高了产率,可作为提高丝裂霉素类似物产率的绿色替代工艺.

Preparation of mitomycin analogs mediated by laccase/lipase and optimization using response surface method

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.