Total Synthesis and Biological Activity of (±)-Guignardin A, (±)-Palmarumycin B9, and Their Derivatives

A strategy for constructing an α-hydroxyl-α-acetonyl moiety was described for the total synthesis of guignardin A (1), 8-deoxypalmarumycin B9 (2), and palmarumycin B9 (3) via 7-, 8-, and 11-step reactions in 14.9, 1.5, and 0.4% overall yields from 5-methoxy-1-tetralone (1a), chroman-4-one (2a), and 2,5-dimethoxybenzaldehyde (3a) as the starting materials, respectively. The key steps included AlCl3- or NaSEt-mediated demethylation, Davis oxidation, and Wacker oxidation. Their structures were characterized by 1H and 13C NMR, HR-ESI-MS, and X-ray diffraction data. A series of spiromamakone A monobenzo derivatives were designed and synthesized by three diallyl-substituted byproducts via olefin metathesis as the key step. The antifungal investigation indicated that compounds 1l and 2n exhibited excellent inhibitory activities against phytopathogen Rhizoctonia solani with EC50 values of 8.68 and 5.25 μg/mL, respectively. Compound 2n had the destructive and inhibitory effects on the morphology and growth of the hyphae of R. solani.