| Abstract
| - (−)-Merrilactone A [(−)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowthactivity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potentialfor the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. Apart fromits biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here,we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a noveldesymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldolreaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiralcenters of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d servedas a platform for the subsequent functional group manipulations necessary for the construction of (+)-1.Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promotedneurite outgrowth in primary neuronal cultures.
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