Synthesis of Xyloketals, Natural Products from the Mangrove Fungus Xylaria sp

The xyloketal family of compounds was synthesized by condensation of phloroglucinol (7) or 2,4‐dihydroxyacetophenone (15) with the enone 8a or 14 in multistep, one‐pot, domino reactions, leading to the xyloketals and 5‐demethylxyloketals, respectively. In the case of condensation with phloroglucinol (7), the mono‐, bis, and tris adducts 6/18, 2/19, 1/20 are formed; their ratios depend on the ratio of stating materials and reaction time. The ring junction of the pyran and furan rings B and C (at C‐2 and C‐6) is always cis. The cis orientation of the methyl groups at C‐2 and C‐5 is also predominant (8.5:1.5), as found in the natural products. In the bis and tris adducts (2/19, 1/20), the relative orientation of the rings B and C can be syn and anti, with the sterically less demanding anti orientation slightly favored statistically. Xyloketal D (4a) was obtained in the condensation of 15 with enantiomerically enriched enone 8a, confirming the absolute configuration of the natural product. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)