2015 Volume 73 Issue 9 Pages 902-910
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.
