6533b872fe1ef96bd12d2f39

RESEARCH PRODUCT

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

Paloma MarínAinhoa GarcíaNathalie HennuyerBruno FigadèreLaura VilaCarlos Villarroel-vicenteDiego CortesÁLvaro BernabeuNuria CabedoBart StaelsXavier Franck

subject

AgonistSynthetic derivatives[CHIM.ORGA]Chemical Sciences/Organic chemistry010405 organic chemistrymedicine.drug_classStereochemistryOrganic ChemistryHorner–Wadsworth–Emmons reactionGrignard reaction01 natural sciencesBiochemistry0104 chemical sciences3. Good health010404 medicinal & biomolecular chemistrychemistry.chemical_compoundchemistryPrenylationDrug DiscoverySide chainmedicinePPARα/γ activityMoietyPrenylated benzopyransHorner-Wadsworth-Emmons reactionBenzopyrans

description

[Image: see text] We have synthesized series of 2-prenylated benzopyrans as analogues of the natural polycerasoidol, a dual PPARα/γ agonist with anti-inflammatory effects. The prenylated side chain consists of five or nine carbons with an α-alkoxy-α,β-unsaturated ester moiety. Prenylation was introduced via the Grignard reaction, followed by Johnson–Claisen rearrangement, and the α-alkoxy-α,β-unsaturated ester moiety was introduced 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.

yearjournalcountryeditionlanguage
2021-10-06ACS Medicinal Chemistry Letters
https://doi.org/10.1021/acsmedchemlett.1c00400