Total Synthesis of (+)-Lycoricidine and Its 2-Epimer from d-Glucose

Stereoselective total synthesis of antimitotic alkaloid (+)-lycoricidine (1) and its 2-epimer (30) was accomplished starting from d-glucose. The key steps in this synthesis are (i) a catalytic version of the Ferrier rearrangement for the preparation of the optically active substituted cyclohexenone (the C-ring of lycoricidine) and (ii) a Pd-catalyzed intramolecular Heck-type reaction for construction of the phenanthridone skeleton. A preliminary biological assay revealed that the stereochemistry at the 2-position of lycoricidine plays an important role in its cytotoxic activity.