The biosynthesis of fungal metabolites. Part V. Structure of variecoxanthones A, B, and C, metabolites of Aspergillus variecolor; conversion of variecoxanthone A into (±)-de-C-prenylepishamixanthone

Abstract

Variecoxanthones A, B, and C, metabolites of a variant strain of Aspergillus variecolor are shown to be 8-hydroxy-1-hydroxymethyl-3-methyl-2-(3-methylbut-2-enyloxy)-(IV), 8-hydroxy-1-hydroxymethyl-3-methyl-5-(3-methylbut-2-enyl)-2-(3-methylbut-2-enyloxy)-(V), and 5-(2,3-epoxy-3-methylbutyl)-8-hydroxy-1-hydroxy-methyl-2-(3-methylbut-2-enyloxy)-xanthone (VI), respectively. These structures were established by detailed spectroscopic comparisons with shamixanthone (I) and tajixanthone (II) and by hydrogenolysis of variecoxanthone A to 2,8-dihydroxy-1,3-dimethylxanthone (X). Acid-catalysed cyclisation of the variecoxanthone-A-derived compound, 1-formyl-8-hydroxy-3-methyl-2-(3-methylbut-2-enyloxy)xanthone (XI), gave 1,2-cis-2,3-dihydro-1,11-dihydroxy-2-isopropenyl-5-methylpyrano[3,2-a]xanthen-12(1H)-one (XIII). The cis-relationship of the 1- and 2-substituents in this compound and the corresponding trans-relationship in shamixanthone are confirmed by comparison of 1H couplings in the hydrogenated derivatives (XIV) and (III), respectively with those in the synthetic 1,2-cis- and 1,2-trans-2,3-dihydro-1-hydroxy-2-isopropyl-7-methyl-1H-benzopyrans (XVI) and (XVII), respectively, prepared by reduction of the corresponding chromone (XVIII) with sodium borohydride. The relative stereochemistry of compounds (XVI) and (XVII) was determined by lanthanide-induced shift studies on their respective 13C and 1H n.m.r. spectra. The mechanistic and biogenetic implications of the acid-catalysed cyclisation of compound (XI) are discussed.