Dregamine

Dregamine
Names
	IUPAC name Methyl (20α)-3-oxo-19,20-dihydrovobasan-17-oate
	Preferred IUPAC name 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
Identifiers
CAS Number	2299-26-5 ;
3D model (JSmol)	Interactive image ;
ChEBI	CHEBI:141897 ;
ChemSpider	19974575 ;
PubChem CID	12309361 ;
	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-/m0/s1 Key: FFVRRQMGGGTQRH-YWKPPDPDSA-N;
	SMILES CC[C@H]1CN([C@H]2Cc3c4ccccc4[nH]c3C(=O)C[C@@H]1[C@@H]2C(=O)OC)C;
Properties
Chemical formula	C21H26N2O3
Molar mass	354.450 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

Last updated December 05, 2023

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.^[1] The indole alkaloid tabernaemontanine is a closely related structure, differing only in the configuration of the ethyl group in the piperidine ring.^[2] 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.^[3]^[4]

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.^[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.^[6]

Natural occurrence

Dregamine is found in plants of the genera Voacanga (e.g. Voacanga dregei^[1]) and Tabernaemontana including Ervatamia hirta ,^[7] Ervatamia malaccensis ^[8] and Tabernaemontana divaricata .^[9] The latter species is known to produce many other alkaloids including catharanthine, ibogamine and voacristine.^[10]

Research

Plant metabolites have long been studied for their biological activity and alkaloids in particular are major subjects for ethnobotanical research.^[11] Dragamine has been studied, for example as a potential anti-cancer agent,^[12]^[13] for its antimalarial activity^[14] and in antifertility research.^[15] However, the alkaloid itself has not been developed as a drug and is known to be cardiotoxic.^[16]

Related Research Articles

<span class="mw-page-title-main">Voacangine</span> Chemical compound

Voacangine is an alkaloid found predominantly in the root bark of the Voacanga africana tree, as well as in other plants such as Tabernanthe iboga, Tabernaemontana africana, Trachelospermum jasminoides, Tabernaemontana divaricata and Ervatamia yunnanensis. It is an iboga alkaloid which commonly serves as a precursor for the semi-synthesis of ibogaine. It has been demonstrated in animals to have similar anti-addictive properties to ibogaine itself. It also potentiates the effects of barbiturates. Under UV-A and UV-B light its crystals fluoresce blue-green, and it is soluble in ethanol.

Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Containing more than 4100 known different compounds, it is one of the largest classes of alkaloids. Many of them possess significant physiological activity and some of them are used in medicine. The amino acid tryptophan is the biochemical precursor of indole alkaloids.

Vincamine is a monoterpenoid indole alkaloid found in the leaves of Vinca minor, comprising about 25–65% of its indole alkaloids by weight. It can also be synthesized from related alkaloids.

Tabernaemontana corymbosa is a species of plant in the family Apocynaceae. It is found in Brunei, China, Indonesia, Laos, Malaysia, Myanmar, Singapore, Thailand, and Vietnam. Glossy green leaves and faintly sweet scented flower. Flowers continuously all year. Frost tolerant. Grows to about 2 metres. Likes full sun to part shade. A number of cultivars are available.

<span class="mw-page-title-main">Coronaridine</span> Chemical compound

Coronaridine, also known as 18-carbomethoxyibogamine, is an alkaloid found in Tabernanthe iboga and related species, including Tabernaemontana divaricata for which it was named.

<span class="mw-page-title-main">Ibogamine</span> Anti-convulsant, anti-addictive CNS stimulant alkaloid

Ibogamine is an anti-convulsant, anti-addictive, CNS stimulant alkaloid found in Tabernanthe iboga and Crepe Jasmine. Basic research related to how addiction affects the brain has used this chemical.

Voacamine, also known under the older names voacanginine and vocamine, is a naturally occurring dimeric indole alkaloid of the secologanin type, found in a number of plants, including Voacanga africana and Tabernaemontana divaricata. It is approved for use as an antimalarial drug in several African countries. Voacamine exhibits cannabinoid CB1 receptor antagonistic activity.

Tabernaemontana elegans, the toad tree, is a shrub or small tree in the family Apocynaceae. It is native to eastern Africa.

Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group. It is found in the Apocynaceae family of plants including Picralima nitida, Vinca minor and the Aspidosperma.

<span class="mw-page-title-main">Catharanthine</span> Chemical compound

Catharanthine is a terpene indole alkaloid produced by the medicinal plant Catharanthus roseus and Tabernaemontana divaricata. Catharanthine is derived from strictosidine, but the exact mechanism by which this happens is currently unknown. Catharanthine is one of the two precursors that form vinblastine, the other being vindoline.

<span class="mw-page-title-main">Affinine</span> Chemical compound

Affinine is a monoterpenoid indole alkaloid which can be isolated from plants of the genus Tabernaemontana. Structurally it can be considered a member of the vobasine alkaloid family and may be synthesized from tryptophan. Limited pharmacological testing has indicated that it may be an effective inhibitor of both acetylcholinesterase and butyrylcholinesterase.

<span class="mw-page-title-main">Affinisine</span> Chemical compound

Affinisine is a monoterpenoid indole alkaloid which can be isolated from plants of the genus Tabernaemontana. Structurally, it can be considered a member of the sarpagine alkaloid family and may be synthesized from tryptophan via a Pictet-Spengler reaction.

<span class="mw-page-title-main">Apparicine</span> Chemical compound

Apparicine is a monoterpenoid indole alkaloid. It is named after Apparicio Duarte, a Brazilian botanist who studied the Aspidosperma species from which apparicine was first isolated. It was the first member of the vallesamine group of alkaloids to be isolated and have its structure established, which was first published in 1965. It has also been known by the synonyms gomezine, pericalline, and tabernoschizine.

<span class="mw-page-title-main">Tabernaemontanine</span> Chemical compound

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

<span class="mw-page-title-main">Conophylline</span> Chemical compound

Conophylline is a autophagy inducing vinca alkaloid found in several species of Tabernaemontana including Ervatamia microphylla and Tabernaemontana divaricata. Among its many functional groups is an epoxide: the compound where that ring is replaced with a double bond is called conophyllidine and this co-occurs in the same plants.

<span class="mw-page-title-main">Ervaticine</span> Chemical compound

Ervaticine is a 2-acylindole alkaloid. It occurs in Ervatamia coronaria and Tabernaemontana divaricata.

<span class="mw-page-title-main">Vobasine</span> Chemical compound

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

<span class="mw-page-title-main">Voacristine</span> Chemical compound

Voacristine is a indole alkaloid occurring in Voacanga and Tabernaemontana genus. It is also an iboga type alkaloid.

<span class="mw-page-title-main">Vinervine</span> Vinca alkaloid

Vinervine is a monoterpene indole alkaloid of the Vinca sub-group. It is a derivative of akuammicine, with one additional hydroxy (OH) group in the indole portion, hence it is also known as 12-hydroxyakuammicine.

19,20-Dihydroervahanine A is an alkaloid, a natural product which is found in the root of the South-East Asian plant Tabernaemontana divaricata. It inhibits acetylcholinesterase more potently than galantamine in vitro.

References

1 2 Neuss, N.; Cone, Nancy J. (1959). "Alkaloids of apocynaceae IV. Dregamine, a new alkaloid from Voacanga dregei e. M.". Experientia. 15 (11): 414–415. doi:10.1007/BF02157683. PMID 14426722. S2CID 36370634.
↑ Renner, U.; Prins, D. A. (1961). "Voacanga-Alkaloide V. Verknüpfung von Vobasin mit Dregamin und Tabernaemontanin". Experientia. 17 (5): 209. doi:10.1007/BF02160617. PMID 13740864. S2CID 35816536.
↑ 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.
↑ Bombardelli, Ezio; Bonati, Attilio; Gabetta, Bruno; Martinelli, Ernesto M.; Mustich, Giuseppe; Danieli, Bruno (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.
↑ Dewick, Paul M (2002). Medicinal Natural Products. A Biosynthetic Approach. Second Edition. Wiley. pp. 350–359. ISBN 0-471-49640-5.
↑ Kutney, James P.; Eigendorf, Gunter K.; Matsue, Hajime; Murai, Akio; Tanaka, Kiyoshi; Sung, Wing L.; Wada, Kojiro; Worth, Brian R. (1978). "Total synthesis of dregamine and epidregamine. A general route to 2-acylindole alkaloids". Journal of the American Chemical Society. 100 (3): 938–943. doi:10.1021/ja00471a047.
↑ Clivio, Pascale; Richard, Bernard; Deverre, Jean-Robert; Sevenet, Thierry; Zeches, Monique; Le Men-Oliver, Louisette (January 1991). "Alkaloids from leaves and root bark of Ervatamia hirta". Phytochemistry. 30 (11): 3785–3792. doi:10.1016/0031-9422(91)80111-D.
↑ Clivio, Pascale; Richard, Bernard; Zeches, Monique; Le Men-Olivier, Louisette; Goh, Swee Hock; David, Bruno; Sevenet, Thierry (1990). "Alkaloids from the leaves and stem bark of Ervatamia malaccensis". Phytochemistry. 29 (8): 2693–2696. doi:10.1016/0031-9422(90)85216-3.
↑ Kam, Toh-Seok; Pang, Huey-Shen; Lim, Tuck-Meng (2003). "Biologically active indole and bisindole alkaloids from Tabernaemontana divaricata". Organic & Biomolecular Chemistry. 1 (8): 1292–1297. doi:10.1039/B301167D. PMID 12929658.
↑ Kulshreshtha, Ankita; Saxena, Jyoti (2019). "Alkaloids and Non Alkaloids of Tabernaemontana divaricata" (PDF). International Journal of Research and Review. 6 (8): 517–524.
↑ Babiaka, Smith B.; Ntie-Kang, Fidele; Lifongo, Lydia L.; Ndingkokhar, Bakoh; Mbah, James A.; Yong, Joseph N. (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.
↑ Paterna, Angela; Kincses, Annamária; Spengler, Gabriella; Mulhovo, Silva; Molnár, Joseph; Ferreira, Maria-José U. (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.
↑ Ferreira, Maria-José U.; Paterna, Angela (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. doi:10.1007/s11101-019-09615-1. S2CID 184483520.
↑ Bapela, M. Johanna; Heyman, Heino; Senejoux, Francois; Meyer, J.J. Marion (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.
↑ Jain, Sachin; Jain, Avijeet; Deb, Lokesh; Dutt, K.R.; Jain, Deepak Kumar (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.
↑ E. Burrows, George; J. Tyrl, Ronald (29 January 2013). Toxic Plants of North America. pp. 117–118. ISBN 978-0813820347.