Synthesis of 2-Prenylated Alkoxylated Benzopyrans by Horner- Wadsworth-Emmons Olefination with PPARα/γ Agonist Activity

We have synthesized series of 2-prenylated benzopyrans as analogues of the natural polycerasoidol, a dual PPAR alpha/gamma agonist with anti-inflammatory effects. The prenylated side chain consists of five or nine carbons with an alpha-alkoxy-alpha,beta-unsaturated ester moiety. Prenylation was introduced via the Grignard reaction, followed by Johnson-Claisen rearrangement, and the alpha-alkoxy-alpha,beta-unsaturated ester moiety was introduced by the Horner-Wadsworth-Emmons reaction. Synthetic derivatives showed high efficacy to activate both hPPAR alpha and hPPAR gamma as dual PPAR alpha/gamma agonists. These prenylated benzopyrans emerge as lead compounds potentially useful for preventing cardiometabolic diseases.

Automated summary

A series of 2-prenylated benzopyrans were synthesized as analogues of the natural dual PPAR alpha/gamma agonist polycerasoidol, showing high efficacy in activating both hPPAR alpha and hPPAR gamma. These compounds have the potential to be lead compounds for preventing cardiometabolic diseases.