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Record Information
Version1.0
Created at2021-06-20 18:17:58 UTC
Updated at2021-06-30 00:05:08 UTC
NP-MRD IDNP0034622
Secondary Accession NumbersNone
Natural Product Identification
Common Namepronuciferine
Provided ByJEOL DatabaseJEOL Logo
Description(+)-Pronuciferine, also known as milthanthine or N-methylstepharine, belongs to the class of organic compounds known as proaporphines. These are benzylisoquinoline derivatives characterized by the presence of a spirocyclohexane ring that can occur in various oxidation levels, from cyclohexadienone to cyclohexanol (+)-pronuciferine is a secondary metabolite. Secondary metabolites are metabolically or physiologically non-essential metabolites that may serve a role as defense or signalling molecules. In some cases they are simply molecules that arise from the incomplete metabolism of other secondary metabolites. pronuciferine is found in Berberis coletioides, Berberis montana, Cissampelos capensis, Cocculus laurifolius, Glossocalyx brevipes, Gyrocarpus americanus, Hypserpa nitida, Meconopsis cambrica, Peumus boldus, Plumula nelumbensis and Uvaria dulcis. It was first documented in 1968 (PMID: 5683993). Based on a literature review a significant number of articles have been published on (+)-pronuciferine (PMID: 19469512) (PMID: 32852096) (PMID: 31707550) (PMID: 31695616) (PMID: 30189375) (PMID: 29087605).
Structure
Thumb
Synonyms
ValueSource
MilthanthineChEBI
N,O-DimethylcrotonosineChEBI
N-MethylstepharineChEBI
PronuciferinChEBI
Chemical FormulaC19H21NO3
Average Mass311.3810 Da
Monoisotopic Mass311.15214 Da
IUPAC Name(4'R)-10',11'-dimethoxy-5'-methyl-5'-azaspiro[cyclohexane-1,2'-tricyclo[6.3.1.0^{4,12}]dodecane]-1'(12'),2,5,8',10'-pentaen-4-one
Traditional Name(4'R)-10',11'-dimethoxy-5'-methyl-5'-azaspiro[cyclohexane-1,2'-tricyclo[6.3.1.0^{4,12}]dodecane]-1'(12'),2,5,8',10'-pentaen-4-one
CAS Registry NumberNot Available
SMILES
[H]C1=C([H])C2(C([H])=C([H])C1=O)C1=C3C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])C([H])([H])N(C([H])([H])[H])[C@]3([H])C2([H])[H]
InChI Identifier
InChI=1S/C19H21NO3/c1-20-9-6-12-10-15(22-2)18(23-3)17-16(12)14(20)11-19(17)7-4-13(21)5-8-19/h4-5,7-8,10,14H,6,9,11H2,1-3H3/t14-/m1/s1
InChI KeyWUYQEGNOQLRQAQ-CQSZACIVSA-N
Experimental Spectra
Spectrum TypeDescriptionDepositor EmailDepositor OrganizationDepositorDeposition DateView
1D NMR13C NMR Spectrum (1D, 500 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, CDCl3, simulated)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
Predicted Spectra
Spectrum TypeDescriptionDepositor IDDepositor OrganizationDepositorDeposition DateView
1D NMR13C NMR Spectrum (1D, 100 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 125 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 150 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 175 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 225 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 25 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 250 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 50 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR13C NMR Spectrum (1D, 75 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, chcl3, predicted)Wishart LabWishart LabDavid Wishart2021-06-20View Spectrum
Chemical Shift Submissions
Not Available
Species
Species of Origin
Species NameSourceReference
Annona cherimolaKNApSAcK Database
Anomianthus dulcisKNApSAcK Database
Antizoma angustifoliaKNApSAcK Database
Berberis coletioidesJEOL database
    • Fajardo, V., et al, J. Nat. Prod. 72, 1355 (2009)
Berberis montanaLOTUS Database
Berberis sibiricaKNApSAcK Database
Cissampelos capensisLOTUS Database
Cocculus laurifoliusLOTUS Database
Cocculus laurifolius DC.KNApSAcK Database
Croton linearisKNApSAcK Database
Glossocalyx brevipesLOTUS Database
Gyrocarpus americanusLOTUS Database
Hypserpa nitidaLOTUS Database
Meconopsis cambricaLOTUS Database
Nelumbo nuciferaKNApSAcK Database
Orophea hexandraKNApSAcK Database
Papaver caucasicum Marsch.-Bieb.KNApSAcK Database
Papaver fugaxKNApSAcK Database
Papaver spp.KNApSAcK Database
Peumus boldusLOTUS Database
Plumula nelumbensis-
Stephania glabraKNApSAcK Database
Thalictrum pedunculatumKNApSAcK Database
Uvaria dulcisLOTUS Database
Xylopia buxifoliaKNApSAcK Database
Chemical Taxonomy
Description Belongs to the class of organic compounds known as proaporphines. These are benzylisoquinoline derivatives characterized by the presence of a spirocyclohexane ring that can occur in various oxidation levels, from cyclohexadienone to cyclohexanol.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassProaporphines
Sub ClassNot Available
Direct ParentProaporphines
Alternative Parents
Substituents
  • Proaporphine
  • Tetrahydroisoquinoline
  • Indane
  • Anisole
  • Alkyl aryl ether
  • Aralkylamine
  • Benzenoid
  • Ketone
  • Tertiary amine
  • Cyclic ketone
  • Tertiary aliphatic amine
  • Ether
  • Azacycle
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Organic oxide
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Physical Properties
StateNot Available
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
logP2.51ALOGPS
logP2.46ChemAxon
logS-3.4ALOGPS
pKa (Strongest Basic)7.69ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area38.77 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity92.27 m³·mol⁻¹ChemAxon
Polarizability34.64 ųChemAxon
Number of Rings4ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
HMDB IDNot Available
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDC00001905
Chemspider ID173542
KEGG Compound IDC09611
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem CompoundNot Available
PDB IDNot Available
ChEBI ID42
Good Scents IDNot Available
References
General References
  1. Fajardo V, Araya M, Cuadra P, Oyarzun A, Gallardo A, Cueto M, Diaz-Marrero AR, Darias J, Villarroel L, Alvarez C, Mora-Perez Y, Joseph-Nathan P: Pronuciferine N-oxide, a proaporphine N-oxide alkaloid from Berberis coletioides. J Nat Prod. 2009 Jul;72(7):1355-6. doi: 10.1021/np9000976. [PubMed:19469512 ]
  2. Bernauer K: [On the synthesis of pronuciferin and some other proaporphine alkaloids]. Helv Chim Acta. 1968 Jul 10;51(5):1119-29. doi: 10.1002/hlca.19680510514. [PubMed:5683993 ]
  3. Bayazeid O, Nemutlu E, Eylem CC, Yalcin FN: Neuroactivity of naturally occurring proaporphine alkaloid, pronuciferine. J Biochem Mol Toxicol. 2020 Dec;34(12):e22601. doi: 10.1002/jbt.22601. Epub 2020 Aug 27. [PubMed:32852096 ]
  4. Yano M, Nakashima S, Oda Y, Nakamura S, Matsuda H: BBB-permeable aporphine-type alkaloids in Nelumbo nucifera flowers with accelerative effects on neurite outgrowth in PC-12 cells. J Nat Med. 2020 Jan;74(1):212-218. doi: 10.1007/s11418-019-01368-7. Epub 2019 Nov 9. [PubMed:31707550 ]
  5. Zou S, Ge Y, Chen X, Li J, Yang X, Wang H, Gao X, Chang YX: Simultaneous Determination of Five Alkaloids by HPLC-MS/MS Combined With Micro-SPE in Rat Plasma and Its Application to Pharmacokinetics After Oral Administration of Lotus Leaf Extract. Front Pharmacol. 2019 Oct 22;10:1252. doi: 10.3389/fphar.2019.01252. eCollection 2019. [PubMed:31695616 ]
  6. Bayazeid O, Eylem CC, Recber T, Yalcin FN, Kir S, Nemutlu E: An LC-ESI-MS/MS method for the simultaneous determination of pronuciferine and roemerine in some Papaver species. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Oct 1;1096:223-227. doi: 10.1016/j.jchromb.2018.08.020. Epub 2018 Aug 21. [PubMed:30189375 ]
  7. Wu N, Xie H, Fang Y, Liu Y, Xi X, Chu Q, Dong G, Lan T, Wei Y: Isolation and purification of alkaloids from lotus leaves by ionic-liquid-modified high-speed countercurrent chromatography. J Sep Sci. 2018 Jan;41(2):571-577. doi: 10.1002/jssc.201700851. Epub 2017 Dec 5. [PubMed:29087605 ]
  8. Morikawa T, Kitagawa N, Tanabe G, Ninomiya K, Okugawa S, Motai C, Kamei I, Yoshikawa M, Lee IJ, Muraoka O: Quantitative Determination of Alkaloids in Lotus Flower (Flower Buds of Nelumbo nucifera) and Their Melanogenesis Inhibitory Activity. Molecules. 2016 Jul 19;21(7). pii: molecules21070930. doi: 10.3390/molecules21070930. [PubMed:27447599 ]
  9. Fajardo, V., et al. (2009). Fajardo, V., et al, J. Nat. Prod. 72, 1355 (2009). J. Nat. Prod..