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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Total Synthesis of (-)-Illisimonin A Enabled by Pattern Recognition and Olefin Transposition
Bo Xu1, Ziyao Zhang1, Mingji Dai1,2
1Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
None:
We report an asymmetric total synthesis of (-)-illisimonin A, a sesquiterpene natural product with neurotrophic activity. Illisimonin A possesses a unique cage-like 5/5/5/5/5 pentacyclic scaffold containing a trans-pentalene and a norbornane, two highly strained and challenging structural motifs. It also contains seven contiguous fully substituted stereocenters, including three all-carbon quaternary centers, two of which are adjacent. Our synthesis exploits a pattern recognition strategy to identify a 5,6-fused bicyclic intermediate derived from (S)-carvone in two steps as the starting point and leverages five sequential olefin transposition reactions to decorate the bicyclic carbocycle. Other key steps include a tandem Mukaiyama hydration-translactonization to form the γ-butyrolactone and an intramolecular aldol cyclization to close the cage and finally deliver (-)-illisimonin A in 16 steps.
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