Mesembrine is analkaloid primarily derived from the plantSceletium tortuosum, commonly known as kanna. This compound is noted for its psychoactive properties, particularly as aserotonin reuptake inhibitor, which contributes to its potential use in treatingmood disorders andanxiety. Mesembrine has garnered interest in both traditional medicine and modern pharmacology, where it is explored for its effects on enhancing mood and cognitive function.
Kanna itself has a long history of use by indigenous peoples in southern Africa, who utilized it for its mood-enhancing and stress-relieving effects, often consuming it in various forms such as teas or chews.[1][2][3][4]
Rat studies have evaluated effects of kanna extract, findinganalgesic and antidepressant potential.[9] No adverse results were noted for a commercial extract up to 5000 mg/kg daily in rats.[10]
Mesembrine was first isolated and characterized in 1957.[11] It is atricyclic molecule with two bridgeheadchiral carbons located between the five-membered and six-membered rings. The naturally occurring form of mesembrine produced by plants is the levorotatory isomer, (−)-mesembrine, where the carbon atoms at positions 3a and 7a both have the S configuration (3aS,7aS).[12]
Because of its structure and bioactivity, mesembrine has been a target fortotal synthesis over the past 40 years. Over 40 total syntheses have been reported for mesembrine, most of which focused on different approaches and strategies for the construction of the bicyclic ring system and thequaternary carbon.
Shamma's route for total synthesis of (±)-mesembrineYamada's asymmetric total synthesis of (+)-mesembrine
The first total synthesis of mesembrine was reported in 1965.[13] This route has 21 steps, which was among the longest synthetic routes for mesembrine. Key steps involve the construction of the six-membered ketone ring byDiels–Alder reaction, α-allylation for synthesis of the quaternary carbon, and conjugate addition reaction for the final five-membered ring closure. The final product from this route is aracemic mixture of (+)- and (-)-mesembrine.
In 1971, first asymmetric total synthesis of (+)-mesembrine was reported.[14] This synthesis introduced the quaternary carbon atom through an asymmetricRobinson annulation reaction, which was mediated by a chiral auxiliary derived fromL-proline. In the final step, an intramolecular aza-Michael addition produced the fused pyrrolidine ring system.
^Van Wyk BE, Wink M (2017).Medicinal plants of the world: an illustrated scientific guide to important medicinal plants and their uses (Second ed.). CABI. p. 226.ISBN978-1-78639-325-8.
^Smith MT, Crouch NR, Gericke N, Hirst M (March 1996). "Psychoactive constituents of the genus Sceletium N.E.Br. and other Mesembryanthemaceae: a review".Journal of Ethnopharmacology (Review).50 (3):119–130.doi:10.1016/0378-8741(95)01342-3.PMID8691846.
^Krstenansky JL (January 2017). "Mesembrine alkaloids: Review of their occurrence, chemistry, and pharmacology".Journal of Ethnopharmacology (Review).195:10–19.doi:10.1016/j.jep.2016.12.004.PMID27939420.
^Harvey AL, Young LC, Viljoen AM, Gericke NP (October 2011). "Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids".Journal of Ethnopharmacology.137 (3):1124–1129.doi:10.1016/j.jep.2011.07.035.PMID21798331.
^Coetzee DD, López V, Smith C (January 2016). "High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor".Journal of Ethnopharmacology.177:111–116.doi:10.1016/j.jep.2015.11.034.PMID26615766.
^Stafford GI, Pedersen ME, van Staden J, Jäger AK (October 2008). "Review on plants with CNS-effects used in traditional South African medicine against mental diseases".Journal of Ethnopharmacology.119 (3):513–537.doi:10.1016/j.jep.2008.08.010.PMID18775771.
^Loria MJ, Ali Z, Abe N, Sufka KJ, Khan IA (August 2014). "Effects of Sceletium tortuosum in rats".Journal of Ethnopharmacology.155 (1):731–735.doi:10.1016/j.jep.2014.06.007.PMID24930358.
^Bodendorf K, Krieger W (October 1957). "[Alkaloids of Mesembryanthemum tortuosum]".Archiv der Pharmazie und Berichte der Deutschen Pharmazeutischen Gesellschaft (in German).290 (10):441–448.doi:10.1002/ardp.19572901002.PMID13471008.
^Coggon P, Farrier DS, Jeffs PW, McPhail AT (1970). "Absolute configuration of mesembrine and related alkaloids: X-ray analysis of 6-epimesembranol methiodide".Journal of the Chemical Society B: Physical Organic:1267–1271.doi:10.1039/J29700001267.
^Shamma M, Rodriguez HR (1965). "The total synthesis of (±)-mesembrine".Tetrahedron Letters.6 (52):4847–4851.doi:10.1016/S0040-4039(01)89046-8.
^Yamada SI, Otani G (January 1971). "Total synthesis of (+)-mesembrine by asymmetric synthesis with amino acid".Tetrahedron Letters.12 (16):1133–1136.doi:10.1016/S0040-4039(01)96647-X.
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