Tabernaemontanine

Tabernaemontanine

Names
IUPAC name Methyl (20βH)-3-oxo-19,20-dihydrovobasan-17-oate
Systematic IUPAC name Methyl (2S,5S,6S,14S)-5-ethyl-3-methyl-8-oxo-2,3,4,5,6,7,8,9-octahydro-1H-2,6-methanoazeceno[5,4-b]indole-14-carboxylate
Identifiers
CAS Number	2134-98-7
3D model (JSmol)	Interactive image
ChEBI	CHEBI:142075
ChEMBL	ChEMBL564301
ChemSpider	19989912
PubChem CID	12309360
InChI InChI=1S/C21H26N2O3/c1-4-12-11-23(2)17-9-15-13-7-5-6-8-16(13)22-20(15)18(24)10-14(12)19(17)21(25)26-3/h5-8,12,14,17,19,22H,4,9-11H2,1-3H3/t12-,14+,17+,19+/m1/s1 Key: FFVRRQMGGGTQRH-DTPILHQWSA-N
SMILES CC[C@@H]1CN([C@H]2Cc3c4ccccc4[nH]c3C(=O)C[C@@H]1[C@@H]2C(=O)OC)C
Properties [1]
Chemical formula	C21H26N2O3
Molar mass	354.450 g·mol−1
Melting point	207 °C (405 °F; 480 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Tabernaemontanine is a naturally occurring monoterpene indole alkaloid found in several species in the genus Tabernaemontana including Tabernaemontana divaricata .

History

Tabernaemontanine was first reported in 1939 ^[1] but its structure was only fully confirmed in the 1970s as there was confusion in the original literature regarding the configuration of the ethyl group in the piperidine ring of this alkaloid and its isomer dregamine, so that their identities had been reversed. ^{[2] [3] [4]} Both compounds were isolated from plants of the dogbane (Apocynaceae) family including Tabernaemontana coronaria . ^[5] They have structures that are reduced versions of vobasine.

Biosynthesis

Main article: Indole alkaloid § Biosynthesis

As with other Indole alkaloids, the biosynthesis of tabernaemontanine starts from the amino acid tryptophan. This is converted into strictosidine before further elaboration. ^[6]

Natural occurrence

Tabernaemontana divaricata, a source of tabernaemontanin

Tabernaemontanine is found commonly in the genera Tabernaemontana and Kopsia , ^[7] including the species Ervatamia hirta , ^[8] Tabernaemontana elegans ^[9] and Tabernaemontana divaricata . ^{[10] [11]} The latter species is known to produce many other alkaloids including catharanthine, ibogamine and voacristine. ^[12]

Research

Plant metabolites have been of interest for their possible biological activity and alkaloids in particular are major subjects for ethnobotanical research. ^{[13] [14]} Tabernaemontanine has been studied, for example as a potential anti-cancer agent, ^{[15] [16] [17] [18]} for its antimalarial activity ^{[19] [20]} and in antifertility research. ^[21] However, the alkaloid itself has not been developed as a drug.

See also

• Tabernanthine
• Ervaticine

References

1. Glasby JS (1975). "T" (PDF). Encyclopedia of the Alkaloids. pp. 1282–1352. doi:10.1007/978-1-4615-8729-3_12. ISBN   978-1-4615-8731-6.
2. Renner U, Prins DA (1961). "Voacanga-Alkaloide V. Verknüpfung von Vobasin mit Dregamin und Tabernaemontanin". Experientia. 17 (5): 209. doi:10.1007/BF02160617. PMID   13740864. S2CID   35816536.
3. Knox JR, Slobbe J (1975). "Indole alkaloids from Ervatamia orientalis. III. The configurations of the ethyl side chains of dregamine and tabernaemontanine and some further chemistry of the vobasine group". Australian Journal of Chemistry. 28 (8): 1843. doi:10.1071/CH9751843.
4. Bombardelli E, Bonati A, Gabetta B, Martinelli EM, Mustich G, Danieli B (1976). "Structures of tabernaelegantines A–D and tabernaelegantinines a and B, new indole alkaloids from Tabernaemontana elegans". Journal of the Chemical Society, Perkin Transactions 1 (13): 1432–1438. doi:10.1039/P19760001432.
5. Gorman M, Neuss N, Cone NJ, Deyrup JA (1960). "Alkaloids from Apocynaceae. III. Alkaloids of Tabernaemontana and Ervatamia. The Structure of Coronaridine, A New Alkaloid Related to Ibogamine". Journal of the American Chemical Society. 82 (5): 1142–1145. Bibcode:1960JAChS..82.1142G. doi:10.1021/ja01490a031.
6. Edwin Saxton J (15 September 2009). Indoles, Part 4: The Monoterpenoid Indole Alkaloids. John Wiley & Sons. ISBN   9780470188446.
7. Kam TS, Lim KH (2008). Chapter 1 Alkaloids of Kopsia. The Alkaloids: Chemistry and Biology. Vol. 66. pp. 1–111. doi:10.1016/S1099-4831(08)00201-0. ISBN   9780123745200. PMID   19025097.
8. Clivio P, Richard B, Deverre JR, Sevenet T, Zeches M, Le Men-Oliver L (January 1991). "Alkaloids from leaves and root bark of Ervatamia hirta". Phytochemistry. 30 (11): 3785–3792. Bibcode:1991PChem..30.3785C. doi:10.1016/0031-9422(91)80111-D.
9. Van Der Heijden R, Brouwer R, Verpoorte R, Wijnsma R, Van Beek T, Harkes A, Svendsen A (1986). "Indole alkaloids from a callus culture of Tabernaemontana elegans". Phytochemistry. 25 (4): 843–846. Bibcode:1986PChem..25..843V. doi:10.1016/0031-9422(86)80013-9.
10. Arambewela LS, Ranatunge T (1991). "Indole alkaloids from Tabernaemontana divaricata". Phytochemistry. 30 (5): 1740–1741. Bibcode:1991PChem..30.1740A. doi:10.1016/0031-9422(91)84254-P.
11. Kam TS, Pang HS, Lim TM (2003). "Biologically active indole and bisindole alkaloids from Tabernaemontana divaricata". Organic & Biomolecular Chemistry. 1 (8): 1292–1297. doi:10.1039/B301167D. PMID   12929658.
12. Kulshreshtha A, Saxena J (2019). "Alkaloids and Non Alkaloids of Tabernaemontana divaricata" (PDF). International Journal of Research and Review. 6 (8): 517–524.
13. Pratchayasakul W, Pongchaidecha A, Chattipakorn N, Chattipakorn S (April 2008). "Ethnobotany & ethnopharmacology of Tabernaemontana divaricata" (PDF). The Indian Journal of Medical Research. 127 (4): 317–35. PMID   18577786.^{[ permanent dead link ]}
14. Babiaka SB, Ntie-Kang F, Lifongo LL, Ndingkokhar B, Mbah JA, Yong JN (2015). "The chemistry and bioactivity of Southern African flora I: A bioactivity versus ethnobotanical survey of alkaloid and terpenoid classes". RSC Advances. 5 (54): 43242–43267. Bibcode:2015RSCAd...543242B. doi:10.1039/C5RA01912E.
15. Singh B, a Sharma R, k Vyas G (2011). "Antimicrobial, Antineoplastic and Cytotoxic Activities of Indole Alkaloids from Tabernaemontana divaricata (L.) R.Br". Current Pharmaceutical Analysis. 7 (2): 125–132. doi:10.2174/157341211795684844.
16. Paterna A, Kincses A, Spengler G, Mulhovo S, Molnár J, Ferreira MJ (2017). "Dregamine and tabernaemontanine derivatives as ABCB1 modulators on resistant cancer cells". European Journal of Medicinal Chemistry. 128: 247–257. doi: 10.1016/j.ejmech.2017.01.044 . PMID   28189906.
17. Ferreira MJ, Paterna A (2019). "Monoterpene indole alkaloids as leads for targeting multidrug resistant cancer cells from the African medicinal plant Tabernaemontana elegans". Phytochemistry Reviews. 18 (4): 971–987. Bibcode:2019PChRv..18..971F. doi:10.1007/s11101-019-09615-1. S2CID   184483520.
18. Cardoso D, Kincses A, Nove M, Spengler G, Mulhovo S, Aires-de-Sousa J, Dos Santos D, Ferreira M (January 2021). "Alkylated monoterpene indole alkaloid derivatives as potent P-glycoprotein inhibitors in resistant cancer cells". European Journal of Medicinal Chemistry . 210 112985. doi: 10.1016/j.ejmech.2020.112985 . PMID   33189435. S2CID   226971895.
19. Girardot M, Deregnaucourt C, Imbert C, Rasoanaivo P, Mambu L (2012). "Exploration of the mechanism of action of alkaloids with antiparasitic activities from Muntafara sessilifolia". Planta Medica. 78 (11): 21055. Bibcode:2012PlMed..7821055G. doi:10.1055/s-0032-1321055.
20. Bapela MJ, Heyman H, Senejoux F, Meyer JM (2019). "1H NMR-based metabolomics of antimalarial plant species traditionally used by Vha-Venda people in Limpopo Province, South Africa and isolation of antiplasmodial compounds". Journal of Ethnopharmacology. 228: 148–155. doi:10.1016/j.jep.2018.07.022. hdl: 2263/75423 . OSTI   1463337. PMID   30048730. S2CID   51725791.
21. Jain S, Jain A, Deb L, Dutt K, Jain DK (2010). "Evaluation of anti-fertility activity of Tabernaemontana divaricata(Linn) R.Br. Leaves in rats". Natural Product Research. 24 (9): 855–860. doi:10.1080/14786410903314385. PMID   20306358. S2CID   41422612.

Further reading

• Kitajima M, Takayama H (2016). Monoterpenoid Bisindole Alkaloids. The Alkaloids: Chemistry and Biology. Vol. 76. pp. 259–310. doi:10.1016/bs.alkal.2015.09.001. ISBN   9780128046821. PMID   26827885.
• Namjoshi OA, Cook JM (2016). Sarpagine and Related Alkaloids. The Alkaloids: Chemistry and Biology. Vol. 76. pp. 63–169. doi:10.1016/bs.alkal.2015.08.002. ISBN   9780128046821. PMC   4864735 . PMID   26827883.