Anonaine

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Anonaine
Anonaine.svg
Names
IUPAC name
1,2-[Methylenebis(oxy)]-12-nor-6aβ-aporphine
Systematic IUPAC name
(7aR)-6,7,7a,8-Tetrahydro-2H,5H-benzo[g][1,3]benzodioxolo[6,5,4-de]quinoline
Identifiers
3D model (JSmol)
ChemSpider
PubChem CID
  • InChI=1S/C17H15NO2/c1-2-4-12-10(3-1)7-13-15-11(5-6-18-13)8-14-17(16(12)15)20-9-19-14/h1-4,8,13,18H,5-7,9H2/t13-/m1/s1
  • C1CN[C@@H]2CC3=CC=CC=C3C4=C2C1=CC5=C4OCO5
Properties
C17H15NO2
Molar mass 265.312 g·mol−1
Melting point 122–123 °C (252–253 °F; 395–396 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Anonaine is a bioactive noraporphine, present in members of the plant families Magnoliaceae and Annonaceae [1] It is named after the plant it was first extracted from, Annona reticulata , which is commonly known as Anona. [2]

Contents

Extraction from Annonaceae

The alkaloid was first isolated from the bark of the Annona reticulata . It has since been found in Annona squamosa , the leaves of Michelia × alba, Fissistigma latifolium and Goniothalamus australis , among many others. [1] The compound may be obtained by dry roasting the bark of Annona reticulata and extracting with methanol. The methanol is removed and the resulting syrup is then treated with hydrochloric acid and the insoluble salts filtered off. The filtrate can then made basic with NH4OH and extracted with diethyl ether. Shaking the extract with 5% sodium hydroxide and retaining the organic layer removes the phenolic content of the extract. The hydrogen chloride salt is then obtained by mixing with hydrochloric acid and recrystallized from diethyl ether. The free base can then be obtained. [2] The anonaine content of Annona reticulata is approximately 0.12%, based on the weight of the starting dried bark. [3]

Research

Traditional medicines

Anonaine is found in many species of Annonacae, which have been used as traditional medicines for many years. For example, extracts of Annona squamosa have been used as treatments for epilepsy, dysentery, cardiac problems, worm infection, constipation, bacterial infection, fever and ulcers. It appears, however, that anonaine is not active in the treatment of many of these ailments. [4] Studies into the bioactivity of anonaine have revealed various interesting pharmacological activities including antitumour, vasorelaxation, antioxidative, antiparasitic and antimicrobial effects, as well as having an effect on the central nervous system. [1]

Anti-tumour properties

Anonaine is known to inhibit growth in human cervical cancer [5] and human lung carcinoma H1299 cells in vitro . [6] The mechanism by which anonaine induces apoptosis in these cells is believed to occur by several mechanisms: generation of nitric oxide and reactive oxygen species, reduction in intracellular glutathione concentration, activation of caspases and apoptosis-related proteins, and damage to DNA.

Antidepressant properties

Anonaine also displays intense dopamine-uptake inhibitory properties, which can lead to a potential anti-depressant activity. [7] [8]

Synthesis

The starting material is called 5-{2-Nitrobenzyl}-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinoline, PC56692289 (1). [9] It is formed via the amide formation between homopiperonylamine and o-Nitrophenylacetyl chloride [22751-23-1], followed by subsequent Pictet–Spengler reaction.

Anonaine synthesis.svg

Treatment with benzoyl chloride gives the amide (2). The reduction of both the benzoyl group and the nitro group occurs in one step by reduction with diborane to give the benzyl aniline (3). Sandmeyer reaction of the diazonium salt leads to N-benzyl-anonaine, PC171976373 (4). Catalytic hydrogenation cleaves the N-benzyl protecting group, completing the synthesis of anonaine (5). [10] [11]

Biosynthesis: [12]

N-Methyl-Anonaine is called Roemerine  [ de ]. [13] The synthesis pathway can be expected to follow a similar course but the starting material would be Homarylamine.

See also

References

  1. 1 2 3 Li, HT; Wu, HM; Chen, HL; Liu, CM; Chen, CY (2013). "The pharmacological activities of (−)-anonaine". Molecules (Basel, Switzerland). 18 (7): 8257–63. doi: 10.3390/molecules18078257 . PMC   6270643 . PMID   23857128.
  2. 1 2 Santos, A. C. (1930). "Alkaloid from Anona reticulata L.". Philippine Journal of Science. 43 (4): 561–564.
  3. ↑ Barger, G.; Weitnauer, G. (1939). "Konstitution und Synthese des Alkaloids Anonain". Helvetica Chimica Acta (in German). 22 (1): 1036–1047. Bibcode:1939HChAc..22.1036B. doi:10.1002/hlca.193902201131.
  4. ↑ Srivastava, S.; Lal, V. K.; Pant, K. K. (2011). "Medicinal potential of Annona squamosa: At a glance". Journal of Pharmacy Research. 4 (12): 4596–4598.
  5. ↑ Chen, Chung-Yi; Liu, Tsan-Zon; Tseng, Wei-Chang; Lu, Fung-Jou; Hung, Ray-Ping; Chen, Chi-Hung; Chen, Ching-Hsein (August 2008). "(−)-Anonaine induces apoptosis through Bax- and caspase-dependent pathways in human cervical cancer (HeLa) cells". Food and Chemical Toxicology. 46 (8): 2694–2702. doi:10.1016/j.fct.2008.04.024. PMID   18524447.
  6. ↑ Chen, Bing-Hung; Chang, Hsueh-Wei; Huang, Hsuan-Min; Chong, Inn-Wen; Chen, Jia-Shing; Chen, Chung-Yi; Wang, Hui-Min (23 March 2011). "(−)-Anonaine Induces DNA Damage and Inhibits Growth and Migration of Human Lung Carcinoma H1299 Cells". Journal of Agricultural and Food Chemistry. 59 (6): 2284–2290. Bibcode:2011JAFC...59.2284C. doi:10.1021/jf103488j. PMID   21361287.
  7. ↑ Lee, J. J., Jin, C. M., Kim, Y. K., Ryu, S. Y., Lim, S. C., Lee, M. K. (27 February 2008). "Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells". Molecules. 13 (2): 475–487. doi: 10.3390/molecules13020475 . PMC   6245076 . PMID   18305432.
  8. ↑ Protais, P., Arbaoui, J., Bakkali, E.-H., Bermejo, A., Cortes, D. (October 1995). "Effects of Various Isoquinoline Alkaloids on In Vitro 3 H-Dopamine Uptake by Rat Striatal Synaptosomes". Journal of Natural Products. 58 (10): 1475–1484. doi:10.1021/np50124a001.
  9. ↑ Gulland, J. M., Haworth, R. D. (1928). "LXXVII.—Synthetical experiments on the aporphine alkaloids. Part I. A synthesis of 5 : 6-dimethoxy-aporphine". J. Chem. Soc. 0 (0): 581–591. doi:10.1039/JR9280000581.
  10. ↑ Cava, M. P., Dalton, D. R. (April 1966). "An Improved Synthesis of dl-Anonaine". The Journal of Organic Chemistry. 31 (4): 1281–1283. doi:10.1021/jo01342a507.
  11. ↑ Marion, L., Lemay, L., Ayotte, R. (1 January 1950). "THE SYNTHESIS OF dl -ANONAINE". Canadian Journal of Research. 28b (1): 21–25. doi:10.1139/cjr50b-004.
  12. ↑ Barton, D. H. R., Bhakuni, D. S., Chapman, G. M., Kirby, G. W. (1967). "Phenol oxidation and biosynthesis. Part XV. The biosynthesis of roemerine, anonaine, and mecambrine". Journal of the Chemical Society C: Organic: 2134. doi:10.1039/j39670002134.
  13. ↑ Marion, L., Grassie, V. (August 1944). "The Synthesis of l-Roemerine 1". Journal of the American Chemical Society. 66 (8): 1290–1292. doi:10.1021/ja01236a024.
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