Asymmetric Total Syntheses of Aspidodasycarpine, Lonicerine, and the Proposed Structure of Lanciferine

Aspidodasycarpine
and lonicerine are a pair of epimeric aspidophylline-type
alkaloids bearing vicinal quaternary C7 and C16. The first and enantioselective
total syntheses of these molecules are described here. A Ru-catalyzed
asymmetric transfer hydrogenation established the first stereocenter.
An Au-promoted Toste cyclization was exploited to assemble the bridged
tetracyclic core and define the geometry of the exocyclic olefin;
electron deficient (p-CF3C6H4)3P was a suitable ligand for this transformation.
An aldol condensation followed by an intramolecular indole C3 alkylation
constructed the adjacent quaternary C7 and C16 diastereoselectively,
leading to a pentacyclic lactol as an advanced common intermediate
for synthesizing both alkaloids. The proposed structure of lanciferine,
a highly oxidized congener of aspidodasycarpine, was synthesized from
the lactol by tuning the oxidation states of various carbons.