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一种通过响应面法优化的漆酶/脂肪酶催化合成丝裂霉素类似物的一锅法工艺。

A one-pot process for synthesis of mitomycin analogs catalyzed by laccase/lipase optimized by response surface methodology.

作者信息

Zhang Yuanyuan, Yao Quancai, Li Zewen, Yang Fengke, Wang Fanye, Liu Junhong

机构信息

Department of Pharmaceutical Engineering in College of Chemical Engineering Qingdao University of Science and Technology Qingdao P. R. China.

State Key Laboratory Base for Eco-Chemical Engineering in College of Chemical Engineering Qingdao University of Science and Technology Qingdao P. R. China.

出版信息

Eng Life Sci. 2019 Sep 30;19(11):805-814. doi: 10.1002/elsc.201900118. eCollection 2019 Nov.

Abstract

To reach the excellent yield as well as environmental friendliness, an efficient one-pot process for the synthesis of 2-methyl-3-butylaminoyl-1,4-benzoquinone, a mitomycin-like compound by the domino reaction of 2-methyl-1,4-hydroquinone and butylamine using laccase/lipase as co-catalysts, has been developed. In this present study, the process proposed here was further improved by optimizing the relevant factors using the response surface methodology based on Box-Benkhen Design. The optimum condition that afforded the highest yield (98%) of 2-methyl-3-butylaminoyl-1,4-benzoquinone was obtained as follows: molar ratio of amines to hydroquinones 1.16:1, activity ratio of laccase to lipase 1.14:2, and reaction temperature 38.9°C. The results obtained indicate that this process may be useful as a green alternative method for higher yield production of mitomycin analogs.

摘要

为了实现优异的产率以及环境友好性,已开发出一种高效的一锅法工艺,以漆酶/脂肪酶作为共催化剂,通过2-甲基-1,4-对苯二酚与丁胺的多米诺反应合成丝裂霉素样化合物2-甲基-3-丁胺酰基-1,4-苯醌。在本研究中,基于Box-Benkhen设计,采用响应面法对相关因素进行优化,进一步改进了此处提出的工艺。获得2-甲基-3-丁胺酰基-1,4-苯醌最高产率(98%)的最佳条件如下:胺与对苯二酚的摩尔比为1.16:1,漆酶与脂肪酶的活性比为1.14:2,反应温度为38.9℃。所得结果表明,该工艺可能作为一种绿色替代方法用于高产率生产丝裂霉素类似物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b32d/6999360/9eeaae3bda7f/ELSC-19-805-g003.jpg

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