Synthesis for Your Nerves

During development, neurons assemble into functional networks by growing out axons and dendrites — collectively called neurites — which connect synaptically to other neurons. Khusiol is a sesquiterpenoid natural product with a tricyclic core. It shares its 3,6,7,7-tetramethyloctahydro-3a,6a-ethanoindene framework with 11-O-debenzoyltashironin, a natural product that promotes neurite outgrowth.

Starting from an enantiomerically enriched cis-1,2-dihydrocatechol, Martin Banwell and co-workers, Australian National University, Canberra, devised a 16-step route to khusiol. Construction of the khusiol framework hinged on an intramolecular Diels–Alder reaction. The synthesis was completed by introducing a key methyl group by conjugate addition of the organocopper species generated in situ from methyl magnesium bromide and CuBr•SMe₂ to an intermediate enone.

This work should enable easier access to the parent compound 11-O-debenzoyltashironin and its congeners, allowing structure–activity studies of this biologically important class of compounds.

• Approaches to the Neurotrophically Active Natural Product 11-O-Debenzoyltashironin: A Chemoenzymatic Total Synthesis of the Structurally Related Sesquiterpene Khusiol,
  M. K. Sharma, M. G. Banwell, A. C. Willis, A. D. Rae,
  Chem. Asian J. 2012.
  DOI: 10.1002/asia.201100913

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