Isolation, synthesis, and neurite outgrowth-promoting activity of illicinin A from the flowers of Illicium anisatum

Two new prenylated C6-C3 compounds, illicinin A (1) and (4S)-illicinone I (2), were isolated from the flowers of Illicium anisatum. The structures of the new compounds were elucidated by spectroscopic methods. The absolute structure of (4S)-illicinone I was determined by comparing its CD spectrum and specific rotation with those of (4S)-illicinone A (4). Illicinin A (1) and 4-allyl-2,6-dimethoxy-3-(3-methylbut-2-enyl)phenol (3) were found to exhibit neurite outgrowth-promoting activity at concentrations ranging from 0.1 to 10 μM in primary cultured rat cortical neurons. Illicinin A and its derivatives were synthesized for structure-activity relationship studies by employing sequential Stille reactions to introduce a prenyl and an allyl group to the benzene ring, thereby indicating that an allylphenyl moiety in the molecule of 1 is essential for its neurotrophic properties.