Vobasine

Vobasine

Names
IUPAC name Methyl (1S,14R,15E,18S)-15-ethylidene-17-methyl-12-oxo-10,17-diazatetracyclo[12.3.1.0^3,11.0^4,9]octadeca-3(11),4,6,8-tetraene-18-carboxylate
Preferred IUPAC name Methyl (19E)-3-oxovobasan-17-oate
Identifiers
CAS Number	2134-83-0^Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:10015
ChemSpider	20119971
KEGG	C09253
PubChem CID	20840254
InChI InChI=1S/C21H24N2O3/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/h4-8,14,17,19,22H,9-11H2,1-3H3/b12-4-/t14-,17-,19-/m0/s1 Key: TYPMTMPLTVSOBU-XJHWFDBESA-N
SMILES C/C=C\1/CN([C@H]2CC3=C(C(=O)C[C@@H]1[C@@H]2C(=O)OC)NC4=CC=CC=C34)C
Properties
Chemical formula	C21H24N2O3
Molar mass	352.434 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Vobasine is a naturally occurring monoterpene indole alkaloid found in several species in the genus Tabernaemontana including Tabernaemontana divaricata.[1]

History

Vobasine was first reported by Renner in 1959 after its isolation from Voacanga africana.[2] The two structurally related compounds, dregamine and tabernaemontanine, where its alkene (=CHCH₃) sidechain was reduced to ethyl groups in two configurations, had their relationship confirmed in the 1970s.[3][4][5] Vobasine has been found in many plants of the dogbane (Apocynaceae) family including Tabernaemontana dichotoma.[6][7]

Synthesis

Biosynthesis

Main article: Indole alkaloid § Biosynthesis

As with other Indole alkaloids, the biosynthesis of vobasine starts from the amino acid tryptophan. This is converted into strictosidine before further elaboration.[8]

Chemical synthesis

The synthesis of alkaloids with the same carbon skeleton as vobasine began in the 1960s[9] and has continued, with some work providing enantiospecific approaches to closely related compounds.[10]

Natural occurrence

Voacanga africana, a source of vobasine

Vobasine is found commonly in the genera Tabernaemontana and Voacanga, including the species Ervatamia hirta,[11] Tabernaemontana elegans,[12] Tabernaemontana divaricata[13][14] and Voacanga africana.[2]

Biochemistry

Plant metabolites have been of interest for their possible biological activity and alkaloids in particular are major subjects for ethnobotanical research.[15][16] Vobasine has been studied, for example as a potential anti-cancer agent[17] and for its hypotensive activity.[18] However, the alkaloid itself has not been developed as a drug.

Toxicity

Very high dose of vobasine at around 300 mg/kg may cause death through CNS and respiratory depression.[19]

See also

• Ervaticine
• Voacristine

References

1. Saxton JE (1987). "Recent progress in the chemistry of indole alkaloids and mould metabolites". Natural Product Reports. 4: 591. doi:10.1039/NP9870400591.
2. Renner U (1959). "Vobasin und Voacryptin, zwei neue Alkaloide aus Voacanga africana Stapf". Experientia. 15 (5): 185–186. doi:10.1007/BF02158691. S2CID 28675532.
3. 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.
4. 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.
5. 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.
6. Raffauf RF, Flagler MB (1960). "Alkaloids of the Apocynaceae". Economic Botany. 14: 37–55. doi:10.1007/BF02859365. S2CID 29538706.
7. Perera P, Samuelsson G, Van Beek T, Verpoorte R (1983). "Tertiary Indole Alkaloids from Leaves of Tabernaemontana dichotoma". Planta Medica. 47 (3): 148–150. doi:10.1055/s-2007-969974. PMID 17404903. S2CID 260283386.
8. Edwin Saxton J (15 September 2009). Indoles, Part 4: The Monoterpenoid Indole Alkaloids. John Wiley & Sons. ISBN 978-0-470-18844-6.
9. Shioiri T, Yamada S (1968). "Studies in the indole series—IV". Tetrahedron. 24 (11): 4159–4175. doi:10.1016/0040-4020(68)88178-5. PMID 5654925.
10. Yang J, Rallapalli SK, Cook JM (2010). "The first enantiospecific total synthesis of the 3-oxygenated sarpagine indole alkaloids affinine and 16-epiaffinine, as well as vobasinediol and 16-epivobasinediol". Tetrahedron Letters. 51 (5): 815–817. doi:10.1016/j.tetlet.2009.12.002.
11. 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.
12. 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.
13. 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.
14. Kulshreshtha A, Saxena J (2019). "Alkaloids and Non Alkaloids of Tabernaemontana divaricata" (PDF). International Journal of Research and Review. 6 (8): 517–524.
15. 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]
16. 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.
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. Perera P, Kanjanapothy D, Sandberg F, Verpoorte R (1985). "Muscle relaxant activity and hypotensive activity of some tabernaemontana alkaloids". Journal of Ethnopharmacology. 13 (2): 165–173. doi:10.1016/0378-8741(85)90004-2. PMID 4021514.
19. "Ethnobotany and ethnopharmacology of Tabernaemontana divaricata".

Further reading

• 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 978-0-12-804682-1. PMC 4864735. PMID 26827883.
• 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 978-0-12-804682-1. PMID 26827885.