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.