lignans and talaumidin

(-)-Talaumidin (1), a 2,5-biaryl-3,4-dimethyltetrahydrofuran lignan isolated from Aristolochia arcuata 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 1 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 1 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, 1e bearing all cis substituents resulted in the most potent neurite-outgrowth promotion.

Topics: Animals; Aristolochia; Cell Differentiation; Cell Line; Furans; Lignans; Nerve Growth Factors; Neurons; PC12 Cells; Rats; Stereoisomerism

( - )-Talaumidin (1) and ( - )-galbelgin (2) have been synthesized via 4-pentenoic acid as a starting material with the overall yield of about 17.8 and 16.9%, respectively. The key steps include Evans asymmetry anti-aldol reaction, TBS protection, hydroboration, oxidation, Friedel-Crafts arylation, etc.

Topics: Aldehydes; Fatty Acids, Monounsaturated; Furans; Lignans; Molecular Structure; Stereoisomerism

Talaumidin, a tetrahydrofuran neolignan isolated from the root of Aristolochia arcuata, was shown to be an intriguing small molecule with neurotrophic activity in the primary culture of rat cortical neurons. Talaumidin can promote both dendrite-like and axon-like process outgrowth of cultured rat cortical neurons at the concentration range of 1-30 microm. Additionally, in the trophic withdrawal model, it can protect cell death caused by the deprivation of serum at the concentration range of 3-30 microm. These data suggest the potential of talaumidin to serve as a promising lead compound for treatment of neurodegenerative diseases.

Topics: Animals; Aristolochia; Barbiturates; Cell Survival; Cells, Cultured; Cerebral Cortex; Female; Furans; Lignans; Neurons; Neuroprotective Agents; Phytotherapy; Plant Extracts; Pregnancy; Rats; Rats, Sprague-Dawley