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.
Chen
Annette P-J
AP
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, 4072 Queensland, Australia.
Müller
C Catharina
CC
Cooper
Helen M
HM
Williams
Craig M
CM
D000818:Animals; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016501:Neurites / Q000502:physiology*; D016716:PC12 Cells; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C544890:4,5-bis-epi-neovibsanin A; C544891:4,5-bis-epi-neovibsanin B; D004224:Diterpenes; D020932:Nerve Growth Factor