Isolation of Core-Oxidized Lupine Alkaloids from the Leaves of <i>Virgilia Oroboides</i> and Semisynthesis of <i>ent-</i> Virgiboidine

Plants of the genus <i>Virgilia</i> are a well-known source of core-oxidized, tricyclic, and tetracylic lupine alkaloids. Reinvestigation of the chemical profile of <i>Virgilia oroboides</i> resulted in the isolation of the known alkaloids virgiline and virgiboidine as well as the unsaturated derivatives 2,3-dehydrovirgiline and 2,3-dehydrovirgiboidine. The latter possess a reactive enamide group, which tends to form <i>N,O-</i>acetal artifacts depending on the extraction and purification conditions. The facile interconversion between these compounds was proven synthetically. Spectroscopic investigations revealed that the tetracyclic alkaloid virgiline preferentially adopts an all-chair conformation in solution despite an axially oriented <i>exo-</i>fused piperidine and an axial hydroxy group. The same conformation was observed in the X-ray structure of 2,3-dehydrovirgiline. A concise semisynthesis of <i>ent-</i>virgiboidine has been developed, providing the alkaloid from the abundant lupine alkaloid cytisine in an overall 5 steps and with a yield of 13%.