Total Synthesis and Structure Revision of (−)-Illisimonin A, a Neuroprotective Sesquiterpenoid from the Fruits of Illicium simonsii
journal contributionposted on 13.08.2019, 19:04 by Alexander S. Burns, Scott D. Rychnovsky
Illisimonin A was isolated from Illicium simonsii and has a previously unreported tricyclic carbon framework. It displayed neuroprotective effects against oxygen-glucose deprivation-induced cell injury in SH-SY5Y cells. It incorporates a highly strained trans-pentalene ring system. We report the first synthesis of (±)-illisimonin A. Notable steps in the route include a 1,3-dioxa-2-silacyclohexene templated Diels–Alder cycloaddition and type-3 semipinacol rearrangement to generate the trans-pentalene. The final step is an iron-catalyzed C–H oxidation. The synthetic route is robust, with 94 mg of racemic material prepared in a single pass. Resolving an intermediate enabled the synthesis of natural (−)-illisimonin A. The absolute configuration of (−)-illisimonin A was revised to 1S,4S,5S,6S,7R,9R,10R based on the X-ray structure of a heavy-atom analogue.
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illisimoninIllicium simonsii Illisimonintype -3 semipinacol rearrangementTotal SynthesisSH-SY 5Y cellsoxygen-glucose deprivation-induced cell injuryNeuroprotective Sesquiterpenoidracemic material94 mgIllicium simonsiisynthesisNotable stepsX-ray structureneuroprotective effectsheavy-atom analoguetrans-pentalene ring systemStructure Revisiontricyclic carbon framework