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

Ainhoa García (1) , Laura Vila (1) , Paloma Marín (1) , Álvaro Bernabeu (1) , Carlos Villarroel-Vicente (1) , Nathalie Hennuyer (2) , Bart Staels (2) , Xavier Franck (3) , Bruno Figadère (4) , Nuria Cabedo (1) , Diego Cortes (1)

1 UV - Universitat de València
2 RNMCD - Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U1011
3 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
4 BioCIS - Biomolécules : Conception, Isolement, Synthèse

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

Mots clés: Prenylated benzopyrans; Horner-Wadsworth-Emmons reaction; PPARα/γ activity

Domaines: Chimie organique

Ainhoa García, Laura Vila, Paloma Marín, Álvaro Bernabeu, Carlos Villarroel-Vicente, et al.. Synthesis of 2-Prenylated Alkoxylated Benzopyrans by Horner-Wadsworth-Emmons olefination with PPARα/γ Agonist Activity. ACS Medicinal Chemistry Letters, 2021, ⟨10.1021/acsmedchemlett.1c00400⟩. ⟨hal-03373981⟩