Efficient Synthesis of the Fungal Phytotoxin (±)-3-Deoxyradicinin

An efficient synthesis of phytotoxin (±)-3-deoxyradicinin was developed from commercially available 4-hydroxy-6-methyl-2H-pyran-2-one. The propenyl side chain was introduced through regioselective bromination followed by Horner–Wadsworth–Emmons olefination, while the second pyranone ring was constructed via a Lewis acid-catalyzed reaction with crotonic acid. The synthetic route was designed according to the principles of operational simplicity, with the aim of minimizing the use of hazardous reagents and solvents, as well as demanding purification procedures and cryogenic conditions. These objectives were successfully achieved for most of the synthetic sequence, with the use of CCl4 in the bromination step representing the main remaining limitation. Four of the six steps were successfully performed on a gram scale, demonstrating the practical potential of the route for a possible scale-up. In addition, a practical synthesis of the natural product 5,6-dehydrokawain was established. Overall, 319 mg of (±)-3-deoxyradicinin were obtained in 23% overall yield, providing a practical approach with reduced reliance on hazardous reagents and low-temperature conditions. This synthetic strategy therefore represents a useful platform for further scale-up of 3-deoxyradicinin preparation and for the synthesis of structurally related analogues.