Mesembrine: The archetypal psycho-active Sceletium alkaloid

Area of Science:

• Natural Products Chemistry
• Medicinal Chemistry
• Organic Synthesis

Background:

• (-)-Mesembrine is a chiral alkaloid found in Sceletium species, traditionally used for central nervous system disorders.
• Mesembrine is a potent serotonin transporter (SERT) inhibitor, surpassing fluoxetine (Prozac) in potency.
• Its unique aryloctahydroindole skeleton and quaternary stereocenter make it a target for synthetic chemistry.

Purpose of the Study:

• To review the distribution, structural elucidation, chemotaxonomy, biosynthesis, and biological activities of (-)-mesembrine.
• To cover recent advancements in the organic synthesis of (-)-mesembrine, its enantiomer, and racemate.
• To highlight the significance of mesembrine in both traditional medicine and modern pharmacology.

Main Methods:

• Literature review of scientific publications on (-)-mesembrine.
• Analysis of binding assay data comparing mesembrine and fluoxetine.
• Examination of synthetic strategies for mesembrine and its related compounds.

Main Results:

• (-)-Mesembrine exhibits potent inhibition of the serotonin transporter (SERT).
• The complex stereochemistry of mesembrine presents a significant challenge and interest in synthetic organic chemistry.
• Research has elucidated its distribution, structure, biosynthesis, and biological effects, leading to commercialization.

Conclusions:

• (-)-Mesembrine is a pharmacologically significant natural product with potential for treating central nervous system disorders.
• Ongoing synthetic efforts continue to explore efficient routes to mesembrine and its analogs.
• The review consolidates current knowledge on (-)-mesembrine, emphasizing its multidisciplinary importance.