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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.
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.
The Myrioneuron alkaloids are a relatively small family of plant-derived alkaloids that present an intriguing array of structural intricacy and biological properties. As such, these natural products have drawn interest from the synthetic community, resulting in creative total syntheses of several family members. This review showcases recent synthetic efforts towards these polycyclic alkaloids.
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