Organic Chemistry

Symmetry-Driven Total Synthesis of Myrioneurinol

Authors

Abstract

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.

Content

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Supplementary material

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Supporting Information
Experimental Procedures, Additional Synthetic Studies, Details of X-ray Analyses, and Copies of NMR Spectra.