We
describe here the diastereocontrolled formal racemic syntheses
of tricyclic marine alkaloids, lepadiformines A, B, and C as well
as their C2 epimers, featuring divergent and stereoselective syntheses
of the N-acetyl-8a-cyanodecahydroquinoline frameworks
and the base-mediated intramolecular cyclization to establish the
spiral quaternary center of the tricyclic framework from sterically
well-defined α-aminonitrile 2. The approach allows
us to accomplish the tricyclic core structure efficiently from readily
available starting materials through simple operations. An unexpected
pair of consecutive epimerizations at two contiguous stereocenters
is observed on the basis of single-crystal X-ray analyses of the intermediates
and derivatives. The findings have been successfully applied to the
total synthesis of 2-epi-lepadiformine C. The epimerization
mechanism has been elucidated through a series of deuterium-labelling-controlled
experiments.