One-Step Synthesis of 4-Octyl Itaconate through the Structure Control of Lipase,The Journal of Organic Chemistry

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One-Step Synthesis of 4-Octyl Itaconate through the Structure Control of Lipase
The Journal of Organic Chemistry ( IF 3.3 ) Pub Date : 2021-06-04 , DOI: 10.1021/acs.joc.0c02995
Changsheng Liu ₁ , Yilin Wang ₁ , Jiahao Liu ₁ , An'nan Chen ₁ , Juntao Xu ₁ , Renwei Zhang ₁ , Fang Wang ₁ , Kaili Nie ₁ , Li Deng ₁

Affiliation

4-Octyl itaconate is a novel antiviral and immunoregulatory small molecule showing great potential in the treatment of various autoimmune diseases and viral infections. It is difficult to selectively esterify the C4 carboxyl group of itaconate acid via one-step direct esterification using chemical catalysts, while the two-step route with itaconic anhydride as an intermediate is environmentally unfriendly and costly. This research investigated the one-step and green synthesis of 4-octyl itaconate through the structure control of lipase, obtaining 4-octyl itaconate with over 98% yield and over 99% selectivity. Multiscale molecular dynamics simulations were applied to investigate the reaction mechanism. The cavity pocket of lipases resulted in a 4-octyl itaconate selectivity by affecting distribution of substrates toward the catalytic site. Toluene could enhance monoesterification in the C4 carboxyl group and contribute to a nearly 100% conversion from itaconate acid into 4-octyl itaconate by adjusting the catalytic microenvironment around the lipase, producing a shrinkage effect on the channel.

中文翻译：

脂肪酶结构控制一步法合成衣康酸4-辛酯

4-Octyl itaconate 是一种新型抗病毒和免疫调节小分子，在治疗各种自身免疫性疾病和病毒感染方面显示出巨大潜力。使用化学催化剂通过一步直接酯化很难选择性地酯化衣康酸的C4羧基，而以衣康酸酐为中间体的两步路线对环境不友好且成本高。本研究通过脂肪酶的结构控制研究了衣康酸4-辛酯的一步绿色合成，以98%以上的收率和99%以上的选择性获得衣康酸4-辛酯。应用多尺度分子动力学模拟来研究反应机理。脂肪酶的空腔口袋通过影响底物向催化位点的分布导致衣康酸 4-辛酯选择性。

更新日期：2021-06-18

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