The first total synthesis of (±)-neovibsanin B (
6), a novel polyfunctionalized diterpenoid, was established based on an intramolecular Diels-Alder reaction accelerated with 1,3-dimethyl-2-imidazolidinone (DMI) and a subsequent oxa-Michael addition-lactonization reaction. Furthermore we revealed that the neurite outgrowth activity of racemic
6 is almost the same as that of natural (+)-
6. We have also synthesized structurally-simplified neovibsanin derivatives, such as
32, based on the synthetic method developed for the total synthesis of (±)-
6. A fluorescent analog
49 that retains neurite outgrowth activity was synthesized, and its behavior in PC12 cells has been analyzed. We also established the formal synthesis of (+)-
6 based on a newly developed asymmetric Michael addition and palladium (0)-catalyzed carbonylative cyclization.
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