Synthesis of heterocycles bearing 2(5H)-furanone and (S)-naproxen moieties

Abstract

Methods for the synthesis of novel heterocyclic compounds bearing an unsaturated γ-lactone ring and an (S)-naproxen moiety were developed. The O-acylation reactions of 3,4-dihalo-5-hydroxy-2(5H)-furanones with (S)-(+)-2-(6-methoxy-2-naphthyl)propionyl chloride in the presence of Et₃N afforded optically active furanone derivatives bearing an (S)-naproxen moiety at the 5 position of the lactone ring. Optically active 4-arylsulfanyl derivatives of 2(5H)-furanone were obtained by the reaction of the isolated (R,S) stereoisomers of 3,4-dihalofuranones with aromatic thiols. A series of heterocycles were synthesized based on 5-alkoxy- and 5-haloahkoxy-2(5H)-furanones containing an (S)-naproxen moiety in the side chain of the hydroxyethylthio substituent on the carbon atom C(4) of the five-membered ring. The structures of three new heterocycles were determined by X-ray diffraction.