We report a total synthesis of the Myrioneuron alkaloid myrioneurinol enabled by the recognition
of hidden symmetry
within its polycyclic structure. Our approach traces myrioneurinol’s
complex framework back to a symmetrical diketone precursor, a double
reductive amination of which forges its central piperidine unit. By
employing an inexpensive chiral amine in this key desymmetrizing event,
four stereocenters of the natural product including the core quaternary
stereocenter are set in an absolute sense, providing the first asymmetric
entry to this target. Other noteworthy strategic maneuvers include
utilizing a bicyclic alkene as a latent cis-1,3-bis(hydroxymethyl)
synthon and a topologically controlled alkene hydrogenation. Overall,
our synthesis proceeds in 18 steps and ∼1% yield from commercial
materials.