Biomimetic Synthesis of Resorcylate Natural Products Utilizing Late Stage Aromatization: Concise Total Syntheses of the Marine Antifungal Agents 15G256ι and 15G256β

Diketo-1,3-dioxin-2-ones underwent retro-Diels−Alder reaction on heating in toluene at 110 °C to generate α,γ,ϵ-triketo-ketenes. These were trapped with alcohols to provide 2,4,6-triketocarboxylates, which were smoothly aromatized by sequential reaction with potassium carbonate and methanolic hydrogen chloride to give resorcylate esters. The reaction was applied in the total synthesis of the marine antifungal agents 15G256β (1), 15G256ι (2), and 15G256π (3) and the mycotoxin S-(−)-zearalenone (4).

二酮基-1,3-二氧六环-2-酮（Diketo-1,3-dioxin-2-ones）在110℃的甲苯溶剂中加热时，可发生逆狄尔斯-阿尔德反应（retro-Diels−Alder reaction），生成α,γ,ε-三酮基烯酮（α,γ,ϵ-triketo-ketenes）。该类中间体可被醇类捕获，得到2,4,6-三酮基羧酸酯（2,4,6-triketocarboxylates）；后者经碳酸钾与甲醇氯化氢溶液依次处理后，可顺利发生芳构化反应，得到间苯二酚酸酯类产物。本反应已应用于海洋抗真菌剂15G256β（1）、15G256ι（2）、15G256π（3）以及真菌毒素S-(-)-玉米赤霉烯酮（S-(−)-zearalenone，4）的全合成。