vobasine

{{Chembox

| ImageFile = Vobasine.svg

| IUPACName = 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

|PIN = Methyl (19E)-3-oxovobasan-17-oate

|Section1={{Chembox Identifiers

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

| CASNo = 2134-83-0

| PubChem = 20840254

| ChemSpiderID_Ref =

| ChemSpiderID = 20119971

| KEGG = C09253

| UNII_Ref =

| UNII =

| ChEBI = 10015

| ChEMBL =

| StdInChI = 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

| StdInChIKey = 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

}}

|Section2={{Chembox Properties

| Properties_ref =

| C=21 | H=24 | N=2 | O=3

| MeltingPtC =

}}

Vobasine is a naturally occurring monoterpene indole alkaloid found in several species in the genus Tabernaemontana including Tabernaemontana divaricata.{{cite journal |doi=10.1039/NP9870400591 |title=Recent progress in the chemistry of indole alkaloids and mould metabolites |year=1987 |last1=Saxton |first1=J. E. |journal=Natural Product Reports |volume=4 |page=591 }}

History

Vobasine was first reported by Renner in 1959 after its isolation from Voacanga africana.{{cite journal |doi=10.1007/BF02158691 |title=Vobasin und Voacryptin, zwei neue Alkaloide aus Voacanga africana Stapf |year=1959 |last1=Renner |first1=U. |journal=Experientia |volume=15 |issue=5 |pages=185–186 |s2cid=28675532 }} 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.{{cite journal |doi=10.1007/BF02160617 |title=Voacanga-Alkaloide V. Verknüpfung von Vobasin mit Dregamin und Tabernaemontanin |year=1961 |last1=Renner |first1=U. |last2=Prins |first2=D. A. |journal=Experientia |volume=17 |issue=5 |page=209 |pmid=13740864 |s2cid=35816536 }}{{cite journal |doi=10.1071/CH9751843 |title=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 |year=1975 |last1=Knox |first1=JR |last2=Slobbe |first2=J. |journal=Australian Journal of Chemistry |volume=28 |issue=8 |page=1843 }}{{cite journal |doi=10.1039/P19760001432 |title=Structures of tabernaelegantines A–D and tabernaelegantinines a and B, new indole alkaloids from Tabernaemontana elegans |year=1976 |last1=Bombardelli |first1=Ezio |last2=Bonati |first2=Attilio |last3=Gabetta |first3=Bruno |last4=Martinelli |first4=Ernesto M. |last5=Mustich |first5=Giuseppe |last6=Danieli |first6=Bruno |journal=Journal of the Chemical Society, Perkin Transactions 1 |issue=13 |pages=1432–1438 }} Vobasine has been found in many plants of the dogbane (Apocynaceae) family including Tabernaemontana dichotoma.{{cite journal |doi=10.1007/BF02859365 |title=Alkaloids of the Apocynaceae |year=1960 |last1=Raffauf |first1=Robert F. |last2=Flagler |first2=M. B. |journal=Economic Botany |volume=14 |pages=37–55 |s2cid=29538706 }}{{cite journal |doi=10.1055/s-2007-969974 |title=Tertiary Indole Alkaloids from Leaves of Tabernaemontana dichotoma |year=1983 |last1=Perera |first1=Premila |last2=Samuelsson |first2=Gunnar |last3=Van Beek |first3=Teris |last4=Verpoorte |first4=Robert |journal=Planta Medica |volume=47 |issue=3 |pages=148–150 |pmid=17404903 |s2cid=260283386 }}

Synthesis

=Biosynthesis=

As with other Indole alkaloids, the biosynthesis of vobasine starts from the amino acid tryptophan. This is converted into strictosidine before further elaboration.{{cite book |isbn=978-0-470-18844-6 |title=Indoles, Part 4: The Monoterpenoid Indole Alkaloids |last1=Edwin Saxton |first1=J. |date=15 September 2009|publisher=John Wiley & Sons |url=https://books.google.com/books?id=KBmGUvmCOU8C&q=Tabernaemontanine&pg=PA1 }}

=Chemical synthesis=

The synthesis of alkaloids with the same carbon skeleton as vobasine began in the 1960s{{cite journal |doi=10.1016/0040-4020(68)88178-5 |title=Studies in the indole series—IV |year=1968 |last1=Shioiri |first1=T. |last2=Yamada |first2=S. |journal=Tetrahedron |volume=24 |issue=11 |pages=4159–4175 |pmid=5654925 }} and has continued, with some work providing enantiospecific approaches to closely related compounds.{{cite journal |doi=10.1016/j.tetlet.2009.12.002 |title=The first enantiospecific total synthesis of the 3-oxygenated sarpagine indole alkaloids affinine and 16-epiaffinine, as well as vobasinediol and 16-epivobasinediol |year=2010 |last1=Yang |first1=Jie |last2=Rallapalli |first2=Sundari K. |last3=Cook |first3=James M. |journal=Tetrahedron Letters |volume=51 |issue=5 |pages=815–817 }}

Natural occurrence

File:Voacanga Africana 06.jpg

Vobasine is found commonly in the genera Tabernaemontana and Voacanga, including the species Ervatamia hirta,{{cite journal|last1=Clivio|first1=Pascale|last2=Richard|first2=Bernard|last3=Deverre|first3=Jean-Robert|last4=Sevenet|first4=Thierry|last5=Zeches|first5=Monique|last6=Le Men-Oliver|first6=Louisette|title=Alkaloids from leaves and root bark of Ervatamia hirta|journal=Phytochemistry|date=January 1991|volume=30|issue=11|pages=3785–3792|doi=10.1016/0031-9422(91)80111-D|bibcode=1991PChem..30.3785C }} Tabernaemontana elegans,{{cite journal |doi=10.1016/0031-9422(86)80013-9 |title=Indole alkaloids from a callus culture of Tabernaemontana elegans |year=1986 |last1=Van Der Heijden |first1=R. |last2=Brouwer |first2=R.L. |last3=Verpoorte |first3=R. |last4=Wijnsma |first4=R. |last5=Van Beek |first5=T.A. |last6=Harkes |first6=A.A. |last7=Svendsen |first7=A.Baerheim |journal=Phytochemistry |volume=25 |issue=4 |pages=843–846 |bibcode=1986PChem..25..843V }} Tabernaemontana divaricata{{cite journal |doi=10.1039/B301167D |title=Biologically active indole and bisindole alkaloids from Tabernaemontana divaricata |year=2003 |last1=Kam |first1=Toh-Seok |last2=Pang |first2=Huey-Shen |last3=Lim |first3=Tuck-Meng |journal=Organic & Biomolecular Chemistry |volume=1 |issue=8 |pages=1292–1297 |pmid=12929658 }}{{cite journal|url=https://www.ijrrjournal.com/IJRR_Vol.6_Issue.8_Aug2019/IJRR0067.pdf|year=2019|volume=6|issue=8|pages=517–524|first1=Ankita |last1=Kulshreshtha|first2=Jyoti|last2=Saxena|title=Alkaloids and Non Alkaloids of Tabernaemontana divaricata|journal=International Journal of Research and Review}} and Voacanga africana.

== Biochemistry ==

Plant metabolites have been of interest for their possible biological activity and alkaloids in particular are major subjects for ethnobotanical research.{{cite journal | vauthors = Pratchayasakul W, Pongchaidecha A, Chattipakorn N, Chattipakorn S | title = Ethnobotany & ethnopharmacology of Tabernaemontana divaricata | journal = The Indian Journal of Medical Research | volume = 127 | issue = 4 | pages = 317–35 | date = April 2008 | pmid = 18577786 | url = http://medind.nic.in/iby/t08/i4/ibyt08i4p317.pdf }}{{Dead link|date=March 2024 |bot=InternetArchiveBot |fix-attempted=yes }}{{cite journal |doi=10.1039/C5RA01912E |title=The chemistry and bioactivity of Southern African flora I: A bioactivity versus ethnobotanical survey of alkaloid and terpenoid classes |year=2015 |last1=Babiaka |first1=Smith B. |last2=Ntie-Kang |first2=Fidele |last3=Lifongo |first3=Lydia L. |last4=Ndingkokhar |first4=Bakoh |last5=Mbah |first5=James A. |last6=Yong |first6=Joseph N. |journal=RSC Advances |volume=5 |issue=54 |pages=43242–43267 |bibcode=2015RSCAd...543242B }} Vobasine has been studied, for example as a potential anti-cancer agent{{cite journal |doi=10.1007/s11101-019-09615-1 |title=Monoterpene indole alkaloids as leads for targeting multidrug resistant cancer cells from the African medicinal plant Tabernaemontana elegans |year=2019 |last1=Ferreira |first1=Maria-José U. |last2=Paterna |first2=Angela |journal=Phytochemistry Reviews |volume=18 |issue=4 |pages=971–987 |bibcode=2019PChRv..18..971F |s2cid=184483520 }} and for its hypotensive activity.{{cite journal |doi=10.1016/0378-8741(85)90004-2 |title=Muscle relaxant activity and hypotensive activity of some tabernaemontana alkaloids |year=1985 |last1=Perera |first1=Premila |last2=Kanjanapothy |first2=Duangta |last3=Sandberg |first3=Finn |last4=Verpoorte |first4=Robert |journal=Journal of Ethnopharmacology |volume=13 |issue=2 |pages=165–173 |pmid=4021514 }} 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.{{cite web| url=https://www.thefreelibrary.com/Ethnobotany+%26+ethnopharmacology+of+Tabernaemontana+divaricata.-a0181406119| title=Ethnobotany and ethnopharmacology of Tabernaemontana divaricata}}