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Apparicine

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Apparicine
Names

IUPAC name (19E)-2,7,16,17,19,20-Hexadehydro-3,7-seco-6-norcuran
Systematic IUPAC name (2R,4E,5S)-4-Ethylidene-6-methylidene-1,3,4,5,6,7-hexahydro-2,5-ethanoazocino[4,3-b]indole
Identifiers
CAS Number	3463-93-2
3D model (JSmol)	Interactive image
ChEBI	CHEBI:78
ChEMBL	ChEMBL285671
ChemSpider	4444718
KEGG	C09036
PubChem CID	5320486
CompTox Dashboard(EPA)	DTXSID30415108
InChI InChI=1S/C18H20N2/c1-3-13-10-20-9-8-14(13)12(2)18-16(11-20)15-6-4-5-7-17(15)19-18/h3-7,14,19H,2,8-11H2,1H3/b13-3-/t14-/m1/s1 Key: LCVACABZTLIWCE-CRAFIKPXSA-N
SMILES C\C=C1\C[N@]2CC[C@@H]1C(=C)c1[nH]c3ccccc3c1C2
Properties
Chemical formula	C₁₈H₂₀N₂
Molar mass	264.372 g·mol⁻¹
Density	0.945875
logP	3.404
Acidity (pK_a)	8.37
Refractive index (n_D)	1.665
Dipole moment	0.552121
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). Infobox references

Chemical compound

Apparicine is amonoterpenoid tricyclicindole alkaloid.^[1] It is named after Apparicio Duarte, a Brazilianbotanist who studied theAspidosperma species from which apparicine was first isolated.^[2]^[3] It was the first member of the vallesamine group ofindole alkaloids to be isolated and have its structure established,^[3] which was first published in 1965.^[4] It has also been known by the synonymsgomezine,pericalline, andtabernoschizine.^[5]

Biochemistry

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Thebiosynthesis of apparicine anduleine have a similar pathway.

The alkaloid has been isolated from seven species ofAspidosperma.^[6] It is the principal alkaloid found in thecallus ofTabernaemontana elegans, and has also been identified in otherTabernaemontana species, includingT. africana,T. divaricata,T. orientalis, andT. pachysiphon.^[7]^[8] In studies ofT. pachysiphon, it was found that alkaloid content including that of apparicine was greatest in young leaves and leaves receiving greater shade, and varied with leaf age, plant age, and provenance.^[9]

Research onAspidosperma pyricollum has led to the discovery that apparicine isbiosynthesised fromtryptophan by "loss of C-2 and retention of C-3".^[10] The biosynthesis of apparicine requires alteration of the usualtryptamine side chain with loss of C-1.^[1]

Structure determination

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Its structure was established through the methods ofchemical decomposition, and the nascent field ofnuclear magnetic resonance (NMR) decoupling using the¹H isotope of hydrogen.^[11]Ultraviolet–visible spectroscopy showed that apparicine has a similar UV absorption touleine,^[12] and theirchromophores were found to be identical.^[11]

NMR decoupling experiments revealed that apparicine lacks anN-methyl signal and has onemethylenic carbon atom between the nitrogen atom and theindole rings, allowing researchers to distinguish it from uleine.^[12] This was a notable early use of NMR decoupling to determine a chemical structure.^[12] Its carbonskeleton was found to be related but different from that of uleine, and the structures of vallesamine and O-acetyl-vallesamine to be related to apparicine.^[13]

Dehydrogenation of apparicine followed byoxidation withpermanganate allowed location of the twopiperidine ring carbon substituents.^[14]

Applications

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Apparicine may have several potential applications. Incell cultures, it has showncytotoxicity against the experimentallymphocytic leukemia P388 cell line.^[15] It exhibits strong activity againstpoliovirus type 3 (PV3),^[15] and has moderate to strong activity against some humanpathogens.^[16] It is also active atopioid receptors^[15] and has micromolaraffinity foradenosine receptors.^[17] Apparicine has localanalgesic properties.^[16] It inhibited xanthine oxidase as potently as allopurinol (IC₅₀ = 0.65 μM).^[18]

Notes

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^^a ^bHerbert 1983, p. 13.
^Elia 2008, p. 594.
^^a ^bJoule 1983, p. 286.
^Joule et al. 1965, p. 4773.
^Gilbert 1968, p. 273.
^Monteiro 1966, p. 39.
^Verpoorte et al. 1989, p. 139.
^Elia 2008, p. 593.
^Elia 2008, p. 596.
^Shamma 1970, p. 324.
^^a ^bJoule et al. 1980, p. 230.
^^a ^b ^cJoule 1983, p. 287.
^Biemann 1966, p. 40.
^Joule 1983, p. 288.
^^a ^b ^cSchmelzer 2008, p. 592.
^^a ^bMairura & Schmelzer 2008, p. 590.
^Ingkaninan et al. 1999, p. 1441.
^Shi BB, Chen J, Bao MF, Zeng Y, Cai XH (October 2019). "Alkaloids isolated from Tabernaemontana bufalina display xanthine oxidase inhibitory activity".Phytochemistry.166 112060.Bibcode:2019PChem.166k2060S.doi:10.1016/j.phytochem.2019.112060.PMID 31302343.S2CID 196613130.

References

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Biemann, Klaus (1966). "Mass spectrometry of selected natural products". In Zechmeister, L. (ed.).Fortschritte der Chemie organischer Naturstoffe. Vol. 24.Springer-Verlag. pp. 2–98.doi:10.1007/978-3-7091-8143-0_1.ISBN 978-3-7091-8145-4.PMID 5958065.{{cite book}}:|journal= ignored (help)
Elia, J. (2008). "Tabernaemontana pachysiphon Stapf". In Schmelzer, G. H.; Gurib-Fakim, A. (eds.).Medicinal Plants 1.Plant Resources of Tropical Africa. Vol. 11. PROTA Foundation; Backhuys Publishers;CTA. pp. 593–596.ISBN 978-90-5782-204-9.
Gilbert, B. (1968). "The alkaloids ofAspidosperma,Ochrosia,Pleiocarpa,Melodinus, and related genera". In Manske, R. H. F. (ed.).The Alkaloids: Chemistry and Physiology. Vol. 11.Academic Press. pp. 205–306.doi:10.1016/S1876-0813(08)60121-9.ISBN 978-0-12-469511-5.
Herbert, Richard B. (1983). "Structural and biosynthetic relationships". In Saxton, J. Edwin (ed.).Indoles: Part Four: The Monoterpenoid Indole Alkaloids. The Chemistry of Heterocyclic Compounds. Vol. 25.John Wiley & Sons. pp. 1–46.doi:10.1002/9780470186954.ch1.ISBN 0-471-89748-5.
Ingkaninan, K.; Ijzerman, A. P.; Taesotikul, T.; Verpoorte, R. (1999)."Isolation of opioid-active compounds fromTabernaemontana pachysiphon leaves".Journal of Pharmacy and Pharmacology.51 (12):1441–1446.doi:10.1211/0022357991777092.PMID 10678501.S2CID 45544097.
Joule, John A. (1983)."The uleine–ellipticine–vallesamine group". In Saxton, J. Edwin (ed.).Indoles: Part Four: The Monoterpenoid Indole Alkaloids. The Chemistry of Heterocyclic Compounds. Vol. 25. John Wiley & Sons. pp. 265–292.doi:10.1002/9780470186954.ch1.ISBN 0-471-89748-5.
Joule, J. A.; Allen, M. S.; Bishop, D. I.; Harris, M.; et al. (1980). "Approaches to the synthesis of apparicine". In Phillipson, John David; Zenk, M. H. (eds.).Indole and Biogenetically Related Alkaloids. Annual Proceedings of the Phytochemical Society of Europe. Vol. 17. Academic Press. pp. 229–248.ISBN 0-12-554450-2.
Joule, J. A.; Monteiro, H.; Durham, L. J.; Gilbert, B.; et al. (1965). "Alkaloid studies. Part XLVIII. The structure of apparicine, a novel Aspidosperma alkaloid".Journal of the Chemical Society (4):4773–4780.doi:10.1039/JR9650004773.PMID 5891947.
Mairura, F. S.; Schmelzer, G. H. (2008). "Tabernaemontana crassa Benth.". In Schmelzer, G. H.; Gurib-Fakim, A. (eds.).Medicinal Plants 1. Plant Resources of Tropical Africa. Vol. 11. PROTA Foundation; Backhuys Publishers; CTA. pp. 589–592.ISBN 978-90-5782-204-9.
Monteiro, Hugo Jorge (1966).Studies on some indole alkaloids: the structure of vallesiachotamine. apparicine, an indole alkaloid of novel structure. the structure and chemistry of nervobscurine. tubulosine and its chemical correlation with deoxytubulosine, Parts 1–4.
Schmelzer, G. H. (2008). "Tabernaemontana elegans Stapf". In Schmelzer, G. H.; Gurib-Fakim, A. (eds.).Medicinal Plants 1. Plant Resources of Tropical Africa. Vol. 11. PROTA Foundation; Backhuys Publishers; CTA. pp. 592–593.ISBN 978-90-5782-204-9.
Shamma, Maurice (1970). "Alkaloids". In Cain, Cornelius K.; et al. (eds.).Annual Reports in Medicinal Chemistry, 1969. Academic Press. pp. 323–332.doi:10.1016/S0065-7743(08)60353-X.ISBN 978-0-12-040505-3.
Verpoorte, R.; van der Heijden, R.; Schripsema, J.; Sierra, M.; et al. (1989). "Secondary metabolites in cell cultures ofTeabernaemontana species". In Kurz, Wolfgang G. W. (ed.).Primary and Secondary Metabolism of Plant Cell Cultures II. Springer-Verlag. pp. 138–148.doi:10.1007/978-3-642-74551-5_16.ISBN 978-3-642-74553-9.