Synthesis of (+)-Dehydrobulbispermine Analogs

Abstract An eight-step synthesis of a (+)-dehydrobulbispermin analog was developed. Starting from optically active 4-alkylidene-tetrahydroisoquinoline, the Eschenmoser–Claisen rearrangement enabled the introduction of the central quaternary center with complete remote stereocontrol. Subsequent iodolactonization, N-BOC group cleavage, and D-ring closure delivered the key quaternary stereotriads as present in (+)-bulbispermine and (+)-hamayne. Then, methyl lithium addition and protection of the resulting OH group allowed completion of the carbon skeleton. OTBS group removal and TEMPO oxidation afforded a ketoaldehyde, which finally underwent an intramolecular aldol condensation, building up the C ring and the α-crinan-11-ol tetracycle derivatives, which will be used as key intermediates in the bulbispermine and 11-hydroxyvittatine-type α-crinane alkaloid total syntheses.