Asymmetric Total Synthesis of (−)-Lycospidine A

The first asymmetric
total synthesis of the structurally unique Lycopodium alkaloid (−)-lycospidine A, containing
an unprecedented five-membered ring, has been accomplished in only
10 steps with 21.6% overall yield from the known conveniently available
sulfoxide. This protecting-group-free short synthesis relied on the
use of a key amidation/aza-Prins domino cyclization reaction to rapidly
construct the tricyclic skeleton and two continuous stereocenters
(one of which is a bridged quaternary stereocenter). An intramolecular
aldol condensation was successfully utilized to establish the unique
five-membered ring, and a late-stage oxidation inspired by biosynthesis
pathway was adopted to synthesize the diosphenol ring of (−)-lycospidine
A.