Synthesis of Cadiolide Analogues with Potential Antibacterial Activities

The cadiolides belong to the family of butenolides and present diverse biological activity as antimicrobial, anti-inflammatory and antioxidant.1-4 Recent publications also show that the cadiolides are selective, due its potential antibacterial activity and low cytotoxicity.1,5,6 In this sense, we propose the synthesis of new cadiolide analogues in order to discover new antibacterial compounds. For the synthesis of the keto-alkynes (3), the Sonogashira cross coupling was carried out between 1 and 2 (60-90% yield).7 The key step of the synthesis, was the regioselective Diels-Alder cycloaddition/cycloreversion reaction between 3 and 4, followed by hydrolysis, resulting in intermediate lactones (5) (50-80% yield).7 Through vinylogous aldol condensation, the intermediate 5 were converted into seven new methoxylated cadiolide analogues with high stereoselectivity (Z isomer at 50-80% yield).2 Finally, the demethylation afforded other seven new analogues. All analogues will be assaied to evaluate their antibacterial activities.