Total Synthesis and Antifungal Activity of Palmarumycin CP(17) and Its Methoxy Analogues

Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP(17) and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. Demethylation with (CH(3))(3)SiI at ambient temperature resulted in ring A aromatization and acetal cleavage to give rise to binaphthyl ethers. The antifungal activities of these spirobisnaphthalene derivatives were evaluated, and the results revealed that 5 and 9b exhibit EC(50) values of 9.34 µg/mL and 12.35 µg/mL, respectively, against P. piricola.