Stereoselective synthesis of caffeic acid amides via enzyme-catalyzed asymmetric aminolysis reaction

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• 作者：Peiliang Xiao ; Suoqin Zhang ; Huayu Ma ; Aijun Zhang ; Xiaoli Lv ; Liangyu Zheng
• 关键词：Lipase ; Stereoselective synthesis ; Caffeic acid amide ; Aminolysis reaction
• 刊名：Journal of Biotechnology
• 出版年：December, 2013
• 年：2013
• 卷：168
• 期：4
• 页码：552-559
• 全文大小：753 K

文摘

In this study, a new method was developed to prepare enantiopure caffeic acid amides by enzyme-catalyzed asymmetric aminolysis reaction. Methoxymethyl chloride (MOMCl) was first introduced as a protective and esterified reagent to obtain the MOM-protected caffeic acid MOM ester 1d. Aminolysis reaction occurred between 1d and (R, S)-伪-phenylethylamine in the presence of an immobilized lipase (Novozym 435) from Candida antarctica. Compared with the methyl-protected caffeic acid methyl ester 1c, 1d as substrate improved the lipase-catalyzed reaction rate by 5.5-fold. After Novozym 435-catalyzed aminolysis reaction was established, we evaluated the effects of synthesis parameters on the catalytic activity and enantioselectivity of Novozym 435. A reaction conversion rate of 25.5% and an E value of >100 were achieved under the following optimum conditions: reaction solvent, anhydrous isooctane; reaction temperature, 70 掳C; reaction time, 24 h; ester-to-amine substrate molar ratio, 1:40; and enzyme additive amount, 40 mg. Kinetic and thermodynamic analyses were conducted to determine the main factors affecting enantiomeric discrimination. Novozym 435 still showed 80% of its initial activity after recycling five times. Highly optically pure caffeic acid amides with an enantiomeric excess of 98.5% were finally obtained by HCl deprotection. The established enzyme-catalyzed asymmetric aminolysis method in this study might be used to prepare other caffeic acid amides.