dregamine

{{Chembox

| ImageFile = Dregamine.svg

| ImageClass = skin-invert-image

| IUPACName = Methyl (20α)-3-oxo-19,20-dihydrovobasan-17-oate

| PIN = Methyl (2S,5R,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

|Section1={{Chembox Identifiers

| CASNo_Ref =

| CASNo = 2299-26-5

| PubChem = 12309361

| ChemSpiderID_Ref =

| ChemSpiderID = 19974575

| UNII_Ref =

| UNII =

| ChEBI = 141897

| ChEMBL =

| StdInChI = 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-/m0/s1

| StdInChIKey = FFVRRQMGGGTQRH-YWKPPDPDSA-N

| SMILES = CC[C@H]1CN([C@H]2Cc3c4ccccc4[nH]c3C(=O)C[C@@H]1[C@@H]2C(=O)OC)C

}}

|Section2={{Chembox Properties

| C=21 | H=26 | N=2 | O=3

}}

Dregamine is a naturally occurring monoterpene indole alkaloid found in several species in the genus Tabernaemontana including Ervatamia hirta and Tabernaemontana divaricata.

History

Dregamine was first reported in 1959 after its isolation from the apocynaceae Voacanga dregei (wild frangipani), a native small tree of southern Africa.{{cite journal |doi=10.1007/BF02157683 |title=Alkaloids of apocynaceae IV. Dregamine, a new alkaloid from Voacanga dregei e. M. |year=1959 |last1=Neuss |first1=N. |last2=Cone |first2=Nancy J. |journal=Experientia |volume=15 |issue=11 |pages=414–415 |pmid=14426722 |s2cid=36370634 }} The indole alkaloid tabernaemontanine is a closely related structure, differing only in the configuration of the ethyl group in the piperidine ring.{{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 }} Both structures are reduced versions of vobasine. There was confusion in the original literature regarding the configuration of the ethyl group in these molecules, so that their identities had been reversed.{{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 }}

Synthesis

=Biosynthesis=

As with other Indole alkaloids, the biosynthesis of dregamine starts from the amino acid tryptophan. This is converted into strictosidine before further elaboration.{{cite book|author = Dewick, Paul M |title = Medicinal Natural Products. A Biosynthetic Approach. Second Edition|pages=350–359|url = https://books.google.com/books?id=A4zptjOJfKQC&pg=PP1|year = 2002|publisher = Wiley|isbn = 0-471-49640-5}}

=Chemical synthesis=

Tryptophan was used as the starting material for a synthesis of dregamine. Its single chiral center provided the correct absolute stereochemistry required when elaborated to prepare the full multi-ring system of the target product.{{cite journal |doi=10.1021/ja00471a047 |title=Total synthesis of dregamine and epidregamine. A general route to 2-acylindole alkaloids |year=1978 |last1=Kutney |first1=James P. |last2=Eigendorf |first2=Gunter K. |last3=Matsue |first3=Hajime |last4=Murai |first4=Akio |last5=Tanaka |first5=Kiyoshi |last6=Sung |first6=Wing L. |last7=Wada |first7=Kojiro |last8=Worth |first8=Brian R. |journal=Journal of the American Chemical Society |volume=100 |issue=3 |pages=938–943 }}

Natural occurrence

File:Crape Jasmine.jpg

Dregamine is found in plants of the genera Voacanga (e.g. Voacanga dregei) and Tabernaemontana including 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}} Ervatamia malaccensis{{cite journal |doi=10.1016/0031-9422(90)85216-3 |title=Alkaloids from the leaves and stem bark of Ervatamia malaccensis |year=1990 |last1=Clivio |first1=Pascale |last2=Richard |first2=Bernard |last3=Zeches |first3=Monique |last4=Le Men-Olivier |first4=Louisette |last5=Goh |first5=Swee Hock |last6=David |first6=Bruno |last7=Sevenet |first7=Thierry |journal=Phytochemistry |volume=29 |issue=8 |pages=2693–2696 }} and 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 }} The latter species is known to produce many other alkaloids including catharanthine, ibogamine and voacristine.{{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}}

Research

Plant metabolites have long been studied for their biological activity and alkaloids in particular are major subjects for ethnobotanical research.{{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 }} Dragamine has been studied, for example as a potential anti-cancer agent,{{cite journal |doi=10.1016/j.ejmech.2017.01.044 |title=Dregamine and tabernaemontanine derivatives as ABCB1 modulators on resistant cancer cells |year=2017 |last1=Paterna |first1=Angela |last2=Kincses |first2=Annamária |last3=Spengler |first3=Gabriella |last4=Mulhovo |first4=Silva |last5=Molnár |first5=Joseph |last6=Ferreira |first6=Maria-José U. |journal=European Journal of Medicinal Chemistry |volume=128 |pages=247–257 |pmid=28189906 |doi-access=free }}{{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 |s2cid=184483520 }} for its antimalarial activity{{cite journal |doi=10.1016/j.jep.2018.07.022 |title=1H NMR-based metabolomics of antimalarial plant species traditionally used by Vha-Venda people in Limpopo Province, South Africa and isolation of antiplasmodial compounds |year=2019 |last1=Bapela |first1=M. Johanna |last2=Heyman |first2=Heino |last3=Senejoux |first3=Francois |last4=Meyer |first4=J.J. Marion |journal=Journal of Ethnopharmacology |volume=228 |pages=148–155 |pmid=30048730 |osti=1463337|url=https://www.osti.gov/servlets/purl/1463337 |hdl=2263/75423 |hdl-access=free }} and in antifertility research.{{cite journal |doi=10.1080/14786410903314385 |title=Evaluation of anti-fertility activity of Tabernaemontana divaricata(Linn) R.Br. Leaves in rats |year=2010 |last1=Jain |first1=Sachin |last2=Jain |first2=Avijeet |last3=Deb |first3=Lokesh |last4=Dutt |first4=K.R. |last5=Jain |first5=Deepak Kumar |journal=Natural Product Research |volume=24 |issue=9 |pages=855–860 |pmid=20306358 |s2cid=41422612 }} However, the alkaloid itself has not been developed as a drug and is known to be cardiotoxic.{{cite book |last1=E. Burrows |first1=George |last2=J. Tyrl |first2=Ronald |title=Toxic Plants of North America |date=29 January 2013 |isbn=978-0813820347 |pages=117–118 |url=https://books.google.com/books?id=cqwvrIfINWgC&q=dregamine+history&pg=PA117}}