Enantioselective Synthesis of (−)-Jiadifenin, a Potent Neurotrophic Modulator.

The first enantioselective synthesis of (−)-jiadifenin (1), a potent neurite outgrowth promoter isolated from the Illiciumspecies, is described. The synthetic strategy builds upon bicyclic motif 6, which represents the AB ring of the natural product and proceeds in 19 steps and 1.1% overall yield. Key to our approach is a Mn(III)-mediated oxidation reaction of A ring that, following a regio- and diastereoselective α-hydroxylation and methylation sequence, produces the desired functionalities of (−)-jiadifenin. The effect of synthetic 1in NGF-mediated neurite outgrowth was also measured in PC-12 cells. [ABSTRACT FROM AUTHOR]