13 research outputs found
Systematic Asymmetric Synthesis of All Diastereomers of (−)-Talaumidin and Their Neurotrophic Activity
(−)-Talaumidin
(<b>1</b>), a 2,5-biaryl-3,4-dimethyltetrahydrofuran
lignan isolated from <i>Aristolochia arcuata</i> Masters,
shows significant neurite-outgrowth promotion and neuroprotection
in primary cultured rat cortical neurons and in NGF-differentiated
PC12 cells. The four stereogenic centers on the tetrahydrofuran moiety
in <b>1</b> result in the presence of seven diastereomers except
for their enantiomers. In order to investigate the stereochemistry–activity
relationships of the stereoisomers, the systematic synthesis of all
stereoisomers of <b>1</b> was accomplished by employing Evans
aldol, diastereoselective hydroboration, reductive deoxygenation,
and Mitsunobu reactions as key steps. The ability of all of the synthesized
stereoisomers to promote neurite-outgrowth in PC12 and neuronal cells
was evaluated. All stereoisomers exhibited moderate to potent neurotrophic
activities in NGF-differentiated PC12 cells at 30 μM and in
primary cultured rat cortical neuronal cells at 0.01 μM. In
particular, <b>1e</b> bearing all <i>cis</i> substituents
resulted in the most potent neurite-outgrowth promotion