Design and Synthesis of Cyclopropane Congeners of Resolvin E3, an Endogenous Pro-Resolving Lipid Mediator, as Its Stable Equivalents.
Design and Synthesis of Cyclopropane Congeners of Resolvin E3, an Endogenous Pro-Resolving Lipid Mediator, as Its Stable Equivalents.
复制标题
Resolvin E3 的环丙烷同系物的设计和合成，Resolvin E3 是一种内源性促拆分脂质介质，作为其稳定等效物。
DOI：
10.1021/acs.joc.2c01110
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Shuto S
中科院分区：
文献类型：
--
作者：
(2)Arai S;Fujiwara K;Kojima M;Aoki-Saito H;Yatomi M;Saito T;Koga Y;Fukuda H;Watanabe M;Matsunaga S;Hisada T;Shuto S
消解素是促消解脂质介质，具有高效的抗炎作用。然而，由于它们的多不饱和结构，它们对作为药物原型的氧不稳定。为了解决这个问题，我们设计并合成了CP-RvE3作为RvE3的氧化稳定同系物，用顺式环丙烷代替顺式烯烃以避免不稳定的双烯丙基结构。尽管CP-RvE3的氧化稳定性没有提高，但β-CP-RvE3的代谢稳定性是RvE3的3.7倍。因此，我们将 β-CP-RvE3 确定为代谢稳定的等效物。
Resolvins are pro-resolving lipid mediators with highly potent anti-inflammatory effects. Because of their polyunsaturated structures, however, they are unstable to oxygen as a drug prototype. To address this issue, we designed and synthesized CP-RvE3 as oxidatively stable congeners of RvE3 by replacing thecis-olefin with acis-cyclopropane to avoid the unstable bisallylic structure. Although the oxidative stabilities of CP-RvE3 were not improved, β-CP-RvE3 was 3.7 times more metabolically stable than RvE3. Thus, we identified β-CP-RvE3 as a metabolically stable equivalent.