Abstract An eight-step synthesis of a (+)-dehydrobulbispermin analog was developed. Starting from optically active 4-alkylidene-tetrahydroisoquinoline Eschenmoser-Claisen rearrangement enabled introduction of the central quarternary center with complete remote stereocontrol. Subsequent iodolactonization, N-BOC group cleavage and D-ring closure delivered the key quarternary 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 keto aldehyde, which finally underwent intramolecular Aldol condensation building-up the C ring and the α-crinan-11-ol tetracycle derivatives, which will be used as key intermediates in bulbispermine and 11-hydroxyvittatine-type α-crinane alkaloid total syntheses.
Kümmerer et al. (Thu,) studied this question.