Bioactive natural products from the endophytic fungus Ascochyta sp. from Meliotus dentatus: configurational assignment by solid-state CD and TDDFT calculations

Two new metabolites, (4S)-(+)-ascochin (1a) and (S,S)-(+)-ascodiketone (3), together with the known compounds (3R,4R)-(?)-4-hydroxymellein (2), ent-alpha-cyperone (4) and (3S,4R)-(?)-dihydroxy-(6S)-undecyl-alpha-pyranone (5) were isolated from cultures of the of the endophytic fungus Ascochyta sp. The biologically active isocoumarin derivative, (4S)-(+)-ascochin (1a), has an unusual substitution pattern which was confirmed by X-ray diffraction. Its absolute configuration was determined by our solid-state TDDFT CD methodology using the X-ray coordinates as input for the calculation. By catalytic hydrogenation, (4S)-(+)-ascochin was converted into the corresponding (3S,4S)-dihydroisocoumarin derivative 1b. The measured and TDDFT calculated CD spectra enabled studies on the correlation between absolute configuration and n-?* transition Cotton effect.