title: Enantioselective synthesis of (-)-jiadifenin, a potent neurotrophic modulator.
abstract: The first enantioselective synthesis of (-)-jiadifenin (1), a potent neurite outgrowth promoter isolated from the Illicium species, 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 1 in NGF-mediated neurite outgrowth was also measured in PC-12 cells.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0358, USA.
authors.forename: Lynnie
authors.initials: L
authors.lastname: Trzoss
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Lacoske
authors.forename: William C
authors.initials: WC
authors.lastname: Mobley
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Theodorakis
mesh_terms: D000818:Animals; D015394:Molecular Structure; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D018696:Neuroprotective Agents; D012717:Sesquiterpenes; C457979:jiadifenin