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

• DOI: 10.1021/acs.orglett.7b01292
• Publication Date: 2017-06-01T20:44:51Z
• Authors: Nengzhong Wang; Shuo Du; Dong Li; Xuefeng Jiang
• Keywords: Stereocenter; Aspidosperma

A uniformly strategic total synthesis of Aspidosperma alkaloids (+)-vincadifformine, (−)-quebrachamine, (+)-aspidospermidine, (−)-aspidospermine, (−)-pyrifolidine, and nine others from efficiently constructed tricyclic ketone 13 is reported. Highlights these divergent practical syntheses include (i) stereoselective intermolecular [4 + 2] cycloaddition to establish a C–E ring with one all-carbon quaternary stereocenter (C-5) two bridged contiguous cis-stereocenters (C-12 C-19), (ii) Pd/C-catalyzed hydrogenation/deprotection/amidation cascade process assemble the D ring, (iii) Fischer indolization forge A–B ring.