Total synthesis of (+/-)-4,5-bis-epi-neovibsanin A and B: a neurite outgrowth comparison study.

(+/-)-4,5-Bis-epi-neovibsanin A and B were synthesized in 12 steps. The acid-catalyzed, one-pot, five-step cascade reaction was central toward the formation of the tricyclic core. The two diastereomers of natural neovibsanin A and B acted as desirable derivatives for structure-activity relationship studies to probe neurotrophic activity. Both (+/-)-4,5-bis-epi-neovibsanin A and B strongly potentiate neurite outgrowth in NGF-stimulated PC12 cells. Furthermore, the tricyclic core appears to be largely responsible for promoting a biological response.