Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Mesembrine: Difference between pages

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 486593254

| ImageFile1 = Mesembrine.svg

| ImageSize1 = 150

| ImageFile2 = Mesembrine3Dan.gif

| ImageSize2 = 150

| IUPACName = (3a''S'',7a''S'')-3a-(3,4-Dimethoxyphenyl)-1-methyl-2,3,4,5,7,7a-hexahydroindol-6-one

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 468-53-1

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = P5X28MLQ1Z

| PubChem = 394162

| SMILES = CN1CC[C@@]2([C@H]1CC(=O)CC2)C3=CC(=C(C=C3)OC)OC

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 349381

| C=17 | H=23 | N=1 | O=3

'''Mesembrine''' is an [[alkaloid]] present in ''[[Sceletium tortuosum]]'' (kanna).<ref name="pmid8691846">{{cite journal |author1=Smith, M. T. |author2=Crouch, N. R. |author3=Gericke, N. |author4=Hirst, M. | title = Psychoactive constituents of the genus ''Sceletium'' N.E.Br. and other Mesembryanthemaceae: A Review | journal = Journal of Ethnopharmacology | volume = 50 | issue = 3 | pages = 119–130 |date=March 1996 | pmid = 8691846 | doi = 10.1016/0378-8741(95)01342-3 }}</ref> It has been shown to act as a [[serotonin reuptake inhibitor]] (K_i&nbsp;=&nbsp;1.4&nbsp;nM), and has also been found to behave as a weak [[Phosphodiesterase-4 inhibitor|inhibitor of the enzyme phosphodiesterase 4]] (PDE4) (K_i&nbsp;=&nbsp;7,800&nbsp;nM).<ref name="pmid21798331">{{ cite journal |author1=Harvey, A. L. |author2=Young, L. C. |author3=Viljoen, A. M. |author4=Gericke, N. P. | title = Pharmacological actions of the South African medicinal and functional food plant ''Sceletium tortuosum'' and its principal alkaloids | journal = Journal of Ethnopharmacology | volume = 137 | issue = 3 | pages = 1124–1129 |date=October 2011 | pmid = 21798331 | doi = 10.1016/j.jep.2011.07.035 }}</ref> In an in vitro study published in 2015, researchers concluded that "a high-mesembrine Sceletium extract" may exert anti-depressant effects by acting as a [[monoamine releasing agent]]."<ref name="pmid26615766">{{ cite journal |author1=Coetzee, D. D. |author2=López, V. |author3=Smith, C.| title = High-mesembrine Sceletium extract (Trimesemine™) is a monoamine releasing agent, rather than only a selective serotonin reuptake inhibitor. | journal = Journal of Ethnopharmacology | volume = 177 | pages = 111–116 |date=November 2015 | pmid = 26615766 | doi = 10.1016/j.jep.2015.11.034 }}</ref> As such, mesembrine likely plays a dominant role in the [[antidepressant]] effects of kanna.<ref name="pmid18775771">{{cite journal |author1=Stafford, G. I. |author2=Pedersen, M. E. |author3=van Staden, J. |author4=Jäger, A. K. | title = Review on plants with CNS-effects used in traditional South African medicine against mental diseases | journal = Journal of Ethnopharmacology | volume = 119 | issue = 3 | pages = 513–537 |date=October 2008 | pmid = 18775771 | doi = 10.1016/j.jep.2008.08.010 }}</ref> The levorotatory isomer, (−)-mesembrine, is the natural form.<ref>{{cite journal |author1=Coggon, P. |author2=Farrier, D.S. |author3=Jeffs, P.W. |author4=McPhail, A.T. | title = Absolute configuration of mesembrine and related alkaloids: X-ray analysis of 6-epimesembranol methiodide. | journal = J. Chem. Soc. B | pages = 1267–1271| year = 1970 | doi = 10.1039/J29700001267 }}</ref>

Rat studies have evaluated effects of kanna extract, finding analgesic and antidepressant potential.<ref>{{Cite journal|title = Effects of Sceletium tortuosum in rats|date = Aug 8, 2014|journal = J. Ethnopharmacol.|doi = 10.1016/j.jep.2014.06.007|pmid = 24930358|volume=155 |issue = 1|pages=731–5|last1 = Loria|first1 = M. J.|last2 = Ali|first2 = Z|last3 = Abe|first3 = N|last4 = Sufka|first4 = K. J.|last5 = Khan|first5 = I. A.}}</ref> No adverse results were noted for a commercial extract up to 5000&nbsp;mg/kg daily in rats.<ref>{{Cite journal|title = A toxicological safety assessment of a standardized extract of Sceletium tortuosum (Zembrin(®)) in rats|date = Dec 2014|journal = Food Chem. Toxicol.|doi = 10.1016/j.fct.2014.09.017|pmid = 25301237|volume=74 |pages=190–9|last1 = Murbach|first1 = T. S.|last2 = Hirka|first2 = G|last3 = Szakonyiné|first3 = I. P.|last4 = Gericke|first4 = N|last5 = Endres|first5 = J. R.|doi-access = free}}</ref>

Mesembrine has also been identified in ''[[Mesembryanthemum cordifolium]]'', ''[[Delosperma echinatum]]'', and ''[[Oscularia deltoides]]''.<ref>{{cite journal | doi=10.1076/phbi.36.3.173.6350 | title=The Distribution of Mesembrine Alkaloids in Selected Taxa of the Mesembryanthemaceae and their Modification in the Sceletium Derived 'Kougoed' | journal=Pharmaceutical Biology | date=January 1998 | volume=36 | issue=3 | pages=173–179 | last1=Smith | first1=Michael T. | last2=Field | first2=Courtney R. | last3=Crouch | first3=Neil R. | last4=Hirst | first4=Manton | doi-access=free }}</ref>

==Total synthesis==

Mesembrine was first isolated and characterized by Bodendorf, ''et al.'' in 1957.<ref>{{cite journal | author = Bodendorf, K.; Krieger, W., Arch. Pharm. | date = 1957 | volume = 290 | pages = 441 }}</ref> It is a [[tricyclic]] molecule and has two bridgehead [[chiral]] carbons between the five-membered ring and the six-membered ring (highlighted in green in the figure below). Because of its structure and bioactivity, mesembrine has been a target for [[total 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 the [[quaternary carbon]].

:[[File:Structure of Mesembrine.png|thumb|left|400px|Structure of mesembrine]]{{clear left}}

The first total synthesis of mesembrine was reported by Shamma, ''et al.''<ref>{{cite journal | doi = 10.1016/S0040-4039(01)89046-8 | title = The total synthesis of (±)-mesembrine | date = 1965 | last1 = Shamma | first1 = Maurice | last2 = Rodriguez | first2 = Herman R. | journal = Tetrahedron Letters | volume = 6 | issue = 52 | pages = 4847–4851 }}</ref> in 1965. 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 by [[Diels-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 a [[racemic mixture]] of (+)- and (-)-mesembrine.

:[[File:Shamma’s route for total synthesis of (±)-Mesembrine.png|thumb|left|600px|Shamma's route for total synthesis of (±)-mesembrine]]{{clear left}}

In 1971, Yamada, ''et al.''<ref>{{cite journal | author = Yamada, S; Otani, G. | title = Alkaloids from Cassia carnaval speg.: Cassaine and carnavaline (1) | journal = Tetrahedron Lett | date = 1971 | volume = 12 | pages = 1133–1137 | doi = 10.1016/S0040-4039(01)96647-X | pmid = 6046785 }}</ref> reported the first asymmetric total synthesis of (+)-mesembrine. The quaternary carbon was introduced by asymmetric [[Robinson annulation]] reaction mediated by an [[proline|<small>L</small>-proline]] derivative.

:[[File:Yamada’s asymmetric total synthesis of (±)-Mesembrine..png|thumb|left|800px|Yamada's asymmetric total synthesis of (+)-mesembrine]]{{clear left}}

==References==

{{Reflist|2}}

{{Monoamine reuptake inhibitors}}

{{Phosphodiesterase inhibitors}}

[[Category:Antidepressants]]

[[Category:Indole alkaloids]]

[[Category:Ketones]]

[[Category:Monoamine releasing agents]]

[[Category:Phenol ethers]]

[[Category:PDE4 inhibitors]]

[[Category:Serotonin reuptake inhibitors]]

[[Category:Total synthesis]]