Design and Synthesis of Cyclopropane Congeners of Resolvin E3, an Endogenous Pro-Resolving Lipid Mediator, as Its Stable Equivalents

J Org Chem. 2022 Aug 5;87(15):10501-10508. doi: 10.1021/acs.joc.2c01110. Epub 2022 Jul 22.

Abstract

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 the cis-olefin with a cis-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclopropanes* / pharmacology
  • Docosahexaenoic Acids / chemistry
  • Fatty Acids, Unsaturated* / chemistry

Substances

  • 17,18-dihydroxyeicosapentaenoic acid
  • Cyclopropanes
  • Fatty Acids, Unsaturated
  • Docosahexaenoic Acids