Asymmetric Total Syntheses and Structure Revisions of Eurotiumide A and Eurotiumide B, and Their Evaluation as Natural Fluorescent Probes

Asymmetric total syntheses and structure revisions of dihydroisocoumarin-type natural products, eurotiumide A and eurotiumide B have been described. The key features of these total syntheses are the asymmetric Shi epoxidation, regio- and stereoselective epoxide opening, C1 insertion/lactonization cascade reaction for constructing the 4-methoxyisochroman-1-one skeleton. We confirmed the structures and configurations of eurotiumide A and B on the basis of X-ray crystallographic analysis of the key intermediate and revealed that eurotiumide A and B have cis and trans configurations at the H3/H4 positions, which indicates the opposite relationship of the stereochemistry with respect to the previous report. Their absolute configurations were also determined. These natural products are highly fluorescent in several solvents with large Stokes shifts involving the excited-state intramolecular proton transfer mechanism, which is supported by time-dependent density functional theory. Eurotiumide A also displays fluorescence in Bacillus cereus.