Divergent Asymmetric Total Synthesis of (+)-Vincadifformine, (-)-Quebrachamine, (+)-Aspidospermidine, (-)-Aspidospermine, (-)-Pyrifolidine, and Related Natural Products

摘要

A uniformly strategic total synthesis of Aspidosperma alkaloids (+)-vincadifformine, (-)-quebrachamine, (+)-aspidospermidine, (-)-aspidospermine, (-)-pyrifolidline, and nine others from efficiently constructed tricyclic ketone 13 is reported. Highlights of these divefgent and practical syntheses include (i) stereoselective intermolecular [4 + 2] Cydoaddition to establish C-E ring with one all-carbon quaternary stereocenter (C-E) and two bridged contiguous cis-stereocenters (C-12 and C-19), (ii) a Pd/C-catalyzed hydrogenation/deprotection/amidation cascade process to assemble the D ring, and (iii) Fischer indolization to forge the A-B ring.