Akuammicine

Last updated
Akuammicine
Akuammicine Structure.svg
Names
IUPAC name
Methyl (19E)-2,16-didehydrocur-19-en-17-oate
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
PubChem CID
UNII
  • InChI=1S/C20H22N2O2/c1-3-12-11-22-9-8-20-14-6-4-5-7-15(14)21-18(20)17(19(23)24-2)13(12)10-16(20)22/h3-7,13,16,21H,8-11H2,1-2H3/b12-3-/t13-,16-,20+/m0/s1
    Key: AGZMFTKKLPHOMT-DUJTVWLASA-N
  • C123C(=C(C4CC1N(CC3)CC4=CC)C(OC)=O)Nc1c2cccc1
Properties [1]
C20H22N2O2
Molar mass 322.408 g·mol−1
AppearanceColourless solid
Melting point 182 °C (360 °F; 455 K)
Acidity (pKa)7.45
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group. It is found in the Apocynaceae family of plants including Picralima nitida , [1] [2] Vinca minor and the Aspidosperma . [3]

Contents

History

The alkaloids are a large group of natural products which are classified according to the part-structure which members of a particular group contain. Akuammicine is a monoterpene indole alkaloid of the Vinca sub-group which shares a common biosynthesis with other members, namely that they are derived from strictosidine. [4] [5] It was first isolated in 1927 and had been investigated by Sir Robert Robinson and others before its structure was correctly deduced. [1] [6] [7] This was confirmed by X-ray crystallography in 2017. [8]

Natural occurrence

Picralima nitida, a source of akuammicine Picralima Nitida - 05.jpg
Picralima nitida, a source of akuammicine

Akuammicine is found in plants of the Apocynaceae family and was first isolated from Picralima nitida . [1] [2] It has also been reported in Catharanthus roseus . [9]

Synthesis

Biosynthesis

As with other indole alkaloids, the biosynthesis of akuammicine starts from the amino acid tryptophan. This is converted into strictosidine before further elaboration. [4]

Chemical synthesis

Strychnine Strychnine.svg
Strychnine

Akuammicine has been a target for total synthesis, [10] partly because of its relationship to the well-known alkaloid strychnine which has often attracted chemists in academia. [11] [12] [13] [14]

Research

Plant metabolites have long been studied for their biological activity and alkaloids in particular are major subjects for ethnobotanical research. [15] Akuammicine is reported to have effects on glucose uptake [2] and be a κ- and μ-opioid receptor agonist. [3] [16]

See also

Related Research Articles

<span class="mw-page-title-main">Apocynaceae</span> Dogbane and oleander family of flowering plants

Apocynaceae is a family of flowering plants that includes trees, shrubs, herbs, stem succulents, and vines, commonly known as the dogbane family, because some taxa were used as dog poison. Members of the family are native to the European, Asian, African, Australian, and American tropics or subtropics, with some temperate members. The former family Asclepiadaceae is considered a subfamily of Apocynaceae and contains 348 genera. A list of Apocynaceae genera may be found here.

<i>Vinca</i> Genus of flowering plants

Vinca is a genus of flowering plants in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The English name periwinkle is shared with the related genus Catharanthus.

<span class="mw-page-title-main">Vinblastine</span> Chemotherapy medication

Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication, typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's lymphoma, non-small-cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer. It is given by injection into a vein.

<i>Catharanthus roseus</i> Species of flowering plant in the family Apocynaceae

Catharanthus roseus, commonly known as bright eyes, Cape periwinkle, graveyard plant, Madagascar periwinkle, old maid, pink periwinkle, rose periwinkle, is a perennial species of flowering plant in the family Apocynaceae. It is native and endemic to Madagascar, but is grown elsewhere as an ornamental and medicinal plant, and now has a pantropical distribution. It is a source of the drugs vincristine and vinblastine, used to treat cancer. It was formerly included in the genus Vinca as Vinca rosea.

<i>Vinca</i> alkaloid

Vinca alkaloids are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived from the periwinkle plant Catharanthus roseus and other vinca plants. They block beta-tubulin polymerization in a dividing cell.

<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.

<span class="mw-page-title-main">Indole alkaloid</span> Class of alkaloids

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.

<span class="mw-page-title-main">Iridoid</span> Class of chemical compounds

Iridoids are a type of monoterpenoids in the general form of cyclopentanopyran, found in a wide variety of plants and some animals. They are biosynthetically derived from 8-oxogeranial. Iridoids are typically found in plants as glycosides, most often bound to glucose.

Strictosidine synthase (EC 4.3.3.2) is an enzyme in alkaloid biosynthesis that catalyses the condensation of tryptamine with secologanin to form strictosidine in a formal Pictet–Spengler reaction:

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

Akuammine (vincamajoridine) is an indole alkaloid. It is the most abundant alkaloid found in the seeds from the tree Picralima nitida, commonly known as akuamma, comprising 0.56% of the dried powder. It has also been isolated from Vinca major. Akuammine is structurally related to yohimbine, mitragynine and more distantly Voacangine, all of which are alkaloid plant products with pharmacological properties.

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

Ajmalicine, also known as δ-yohimbine or raubasine, is an antihypertensive drug used in the treatment of high blood pressure. It has been marketed under numerous brand names including Card-Lamuran, Circolene, Cristanyl, Duxil, Duxor, Hydroxysarpon, Iskedyl, Isosarpan, Isquebral, Lamuran, Melanex, Raunatin, Saltucin Co, Salvalion, and Sarpan. It is an alkaloid found naturally in various plants such as Rauvolfia spp., Catharanthus roseus, and Mitragyna speciosa.

3α(S)-strictosidine β-glucosidase (EC 3.2.1.105) is an enzyme with systematic name strictosidine β-D-glucohydrolase. It catalyses the following chemical reaction:

<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">Strictosidine</span> Chemical compound

Strictosidine is a natural chemical compound and is classified as a glucoalkaloid and a vinca alkaloid. It is formed by the Pictet–Spengler condensation reaction of tryptamine with secologanin, catalyzed by the enzyme strictosidine synthase. Thousands of strictosidine derivatives are sometimes referred to by the broad phrase of monoterpene indole alkaloids. Strictosidine is an intermediate in the biosynthesis of numerous pharmaceutically valuable metabolites including quinine, camptothecin, ajmalicine, serpentine, vinblastine, vincristine and mitragynine.

<span class="mw-page-title-main">3-Hydroxy-16-methoxy-2,3-dihydrotabersonine</span> Chemical compound

3-Hydroxy-16-methoxy-2,3-dihydrotabersonine is a terpene indole alkaloid produced by Catharanthus roseus. The metabolite is a substrate for 3-hydroxy-16-methoxy-2,3-dihydrotabersonine N-methyltransferase (NMT) which transfers a methyl group to the nitrogen of the indole ring forming desacetoxyvindoline. The enzyme catalyzing the formation of 3-hydroxy-16-methoxy-2,3-dihydrotabersonine from 16-methoxytabersonine is currently unknown, but is a result of hydration of the double bond connecting the 6 and 13 position carbons.

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

Stemmadenine is a terpene indole alkaloid. Stemmadenine is believed to be formed from preakuammicine by a carbon-carbon bond cleavage. Cleavage of a second carbon-carbon bond is thought to form dehydrosecodine. The enzymes forming stemmadenine and using it as a substrate remain unknown to date. It is thought to be intermediate compound in many different biosynthetic pathways such as in Aspidosperma species. Many alkaloids are proposed to be produced through intermediate stemmadenine. Some of them are:

<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">Dregamine</span> Chemical compound

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

References

  1. 1 2 3 4 Robinson, Robert; Thomas, A. F. (1955). "The Alkaloids of Picralima nitida, Stapf, Th. and H. Durand. Part III. A Note on Akuammicine and pseudoAkuammicine". Journal of the Chemical Society (Resumed): 2049. doi:10.1039/jr9550002038. ISSN   0368-1769.
  2. 1 2 3 Shittu, Hafsat; Gray, Alexander; Furman, Brian; Young, Louise (2010). "Glucose uptake stimulatory effect of akuammicine from Picralima nitida (Apocynaceae)". Phytochemistry Letters. 3 (1): 53–55. doi:10.1016/j.phytol.2009.11.003. ISSN   1874-3900.
  3. 1 2 Mitaine, A. C.; Mesbah, K; Richard, B; Petermann, C; Arrazola, S; Moretti, C; Zèches-Hanrot, M; Men-Olivier, L. L. (1996). "Alkaloids from Aspidosperma species from Bolivia". Planta Medica. 62 (5): 458–61. doi:10.1055/s-2006-957939. PMID   17252481. S2CID   260251185.
  4. 1 2 Dewick, Paul M (2002). Medicinal Natural Products. A Biosynthetic Approach. Second Edition. Wiley. pp. 350–359. ISBN   0-471-49640-5.
  5. ↑ Saxton, J. E. (1984). "Recent progress in the chemistry of indole alkaloids and mould metabolites". Natural Product Reports. 1: 21. doi:10.1039/NP9840100021.
  6. ↑ Smith, G. F.; Wróbel, J. T. (1960). "161. Akuamma alkaloids. Part I. Akuammicine". J. Chem. Soc.: 792–795. doi:10.1039/JR9600000792.
  7. ↑ Yagudaev, M. R. (1983). "NMR investigation of alkaloids. IV. 13C NMR spectra and structures of norfluorocurarine, akuammicine, vincanidine, and vinervinine". Chemistry of Natural Compounds. 19 (2): 199–201. doi:10.1007/BF00580558. S2CID   28255077.
  8. ↑ Yahyazadeh, Mahdi; Jerz, Gerold; Selmar, Dirk; Winterhalter, Peter; Jones, Peter G. (2017). "Crystal structure of akuammicine, an indole alkaloid from Catharanthus roseus". Acta Crystallographica Section E. 73 (11): 1658–1661. doi:10.1107/S2056989017014529. PMC   5683484 . PMID   29152344.
  9. ↑ Scott, A.Ian; Mizukami, Hajime; Hirata, Toshifumi; Lee, Siu-Leung (1980). "Formation of catharanthine, akuammicine and vindoline in Catharanthus roseus suspension cells". Phytochemistry. 19 (3): 488–489. doi:10.1016/0031-9422(80)83216-X.
  10. ↑ Jones, Spencer B.; Simmons, Bryon; Mastracchio, Anthony; MacMillan, David W. C. (2011). "Collective synthesis of natural products by means of organocascade catalysis". Nature. 475 (7355): 183–188. doi:10.1038/nature10232. PMC   3439143 . PMID   21753848.
  11. ↑ Ito, Masayuki; Clark, Cameron W.; Mortimore, Michael; Goh, Jane Betty; Martin, Stephen F. (2001). "Biogenetically Inspired Approach to the Strychnos Alkaloids. Concise Syntheses of (±)-Akuammicine and (±)-Strychnine". Journal of the American Chemical Society. 123 (33): 8003–8010. doi:10.1021/ja010935v. PMID   11506556.
  12. ↑ Sirasani, Gopal; Paul, Tapas; Dougherty, William; Kassel, Scott; Andrade, Rodrigo B. (2010). "Concise Total Syntheses of (±)-Strychnine and (±)-Akuammicine". The Journal of Organic Chemistry. 75 (10): 3529–3532. doi:10.1021/jo100516g. PMID   20408591.
  13. ↑ Sirasani, Gopal; Andrade, Rodrigo B. (2013). Total Synthesis of Strychnos Alkaloids Akuammicine, Strychnine, and Leuconicines a and B. Strategies and Tactics in Organic Synthesis. Vol. 9. pp. 1–44. doi:10.1016/B978-0-08-099362-1.00001-1. ISBN   9780080993621.
  14. ↑ Feng, Liang-Wen; Ren, Hai; Xiong, Hu; Wang, Pan; Wang, Lijia; Tang, Yong (2017). "Reaction of Donor-Acceptor Cyclobutanes with Indoles: A General Protocol for the Formal Total Synthesis of (±)-Strychnine and the Total Synthesis of (±)-Akuammicine". Angewandte Chemie International Edition. 56 (11): 3055–3058. doi:10.1002/anie.201611734. PMID   28170147.
  15. ↑ 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.
  16. ↑ Menzies, John R.W; Paterson, Stewart J.; Duwiejua, Mahama; Corbett, Alistair D. (1998). "Opioid activity of alkaloids extracted from Picralima nitida (Fam. Apocynaceae)". European Journal of Pharmacology. 350 (1): 101–108. doi:10.1016/s0014-2999(98)00232-5. PMID   9683021.
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