Unique solvent-dependent atropisomerism of a novel cytotoxic naphthoxanthene antibiotic FD-594

The absolute stereochemistry of FD-594 1, a new cytotoxic antibiotic, was d etermined by X-ray diffraction, and its conformation was studied by CD and NMR spectroscopy. The aglycon part of 1 was found to have (3R,6S,7S) config uration. Particularly interesting was the solvent-dependent atropisomerism of 1 and related compounds. The CD spectra of 1 exhibited in two solvent sy stems almost opposite mirror-image curves depending on the solvent. While a large negative Cotton effect (Delta epsilon = -33.9, 279 nm) was observed in CHCl3, a similar positive Cotton effect (Delta epsilon = 38.9, 279 nm) a ppeared in methanol most probably due to dramatic conformational changes. S imilar chiroptical reversal was observed in aglycon 2 and aglycon methyl et her 4. These results can be best described in terms of solvent-dependent at ropisomerism. This constitutes the first observation of solvent-dependent a tropisomerism of a natural product. The crucial factor that perturbs the st able conformation in different solvents is discussed on the basis of molecu lar mechanics calculations.