Dihydrokavain (CHEM017388)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesXML
Record Information
Version1.0
Creation Date2016-05-22 04:17:43 UTC
Update Date2016-11-09 01:15:35 UTC
Accession NumberCHEM017388
Identification
Common NameDihydrokavain
ClassSmall Molecule
DescriptionMarindinin is found in beverages. Marindinin is found in the roots of kava (Piper methysticum). FDA advises against use of kava in food due to potential risk of severe liver damage (2002
Contaminant Sources
  • FooDB Chemicals
  • ToxCast & Tox21 Chemicals
Contaminant TypeNot Available
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
4-Methoxy-6-(2-phenylethyl)-5,6-dihydro-2H-pyran-2-oneHMDB
5,6-Dihydro-4-methoxy-6-phenethyl-2H-pyran-2-oneHMDB
7,8-Dihydro-kawainHMDB
7,8-DihydrokavainHMDB
7,8-DihydrokawainHMDB
Dihydro-kavainHMDB
Dihydro-kawainHMDB
DihydrokavainHMDB
DihydrokawainHMDB
Chemical FormulaC14H16O3
Average Molecular Mass232.275 g/mol
Monoisotopic Mass232.110 g/mol
CAS Registry Number587-63-3
IUPAC Name4-methoxy-6-(2-phenylethyl)-5,6-dihydro-2H-pyran-2-one
Traditional Namedihydrokavain
SMILESCOC1=CC(=O)OC(CCC2=CC=CC=C2)C1
InChI IdentifierInChI=1S/C14H16O3/c1-16-13-9-12(17-14(15)10-13)8-7-11-5-3-2-4-6-11/h2-6,10,12H,7-9H2,1H3
InChI KeyVOOYTQRREPYRIW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as kavalactones. These are lactones, which is structurally characterized by a benzene ring and a pyranone moiety, linked to each other to form a 4-methoxy-6-(2-phenylethyl)-2H-pyran-2-one skeleton.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassKavalactones
Sub ClassNot Available
Direct ParentKavalactones
Alternative Parents
Substituents
  • Kavalactone
  • Dihydropyranone
  • Monocyclic benzene moiety
  • Pyran
  • Benzenoid
  • Vinylogous ester
  • Alpha,beta-unsaturated carboxylic ester
  • Enoate ester
  • Lactone
  • Carboxylic acid ester
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Organoheterocyclic compound
  • Oxacycle
  • Carbonyl group
  • Organooxygen compound
  • Organic oxide
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginNot Available
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateNot Available
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.041 g/LALOGPS
logP2.91ALOGPS
logP2.56ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)16.43ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area35.53 ŲChemAxon
Rotatable Bond Count4ChemAxon
Refractivity66.4 m³·mol⁻¹ChemAxon
Polarizability25.35 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9500000000-c5600c77821baced5710Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0590000000-cdb149e3549ebc48df46Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0159-1900000000-5f9a595ba9bd7424a337Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0kvo-9800000000-26a9688f8a322373262eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-0690000000-1a1d0e9cea6a50a7b0d4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000x-9440000000-113393a90e3c0732dd4dSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0536-9600000000-9fba2cac2d065519983cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0900000000-4e868adf7649a278b06cSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-da558f14842069aee8f2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9200000000-6e26bb77b8bdc63aebdaSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0159-1960000000-1c868b5a6476e7791710Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kf-7900000000-69a5b13079ddea7eefc6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00mo-9500000000-737b2befa46a626ef81cSpectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityNot Available
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not Available
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB0029504
FooDB IDFDB000639
Phenol Explorer IDNot Available
KNApSAcK IDC00029583
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkDihydrokavain
Chemspider ID88817
ChEBI ID862793
PubChem Compound ID98356
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
1. Backhauss C, Krieglstein J: Extract of kava (Piper methysticum) and its methysticin constituents protect brain tissue against ischemic damage in rodents. Eur J Pharmacol. 1992 May 14;215(2-3):265-9.
2. Boonen G, Haberlein H: Influence of genuine kavapyrone enantiomers on the GABA-A binding site. Planta Med. 1998 Aug;64(6):504-6.
3. Hu L, Jhoo JW, Ang CY, Dinovi M, Mattia A: Determination of six kavalactones in dietary supplements and selected functional foods containing Piper methysticum by isocratic liquid chromatography with internal standard. J AOAC Int. 2005 Jan-Feb;88(1):16-25.
4. de Jager LS, Perfetti GA, Diachenko GW: LC-UV and LC-MS analysis of food and drink products containing kava. Food Addit Contam. 2004 Oct;21(10):921-34.
5. Weiss J, Sauer A, Frank A, Unger M: Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug Metab Dispos. 2005 Nov;33(11):1580-3. Epub 2005 Jul 28.
6. Kato K, Motodate S, Mochida T, Kobayashi T, Akita H: Intermolecular methoxycarbonylation of terminal alkynes catalyzed by palladium(II) bis(oxazoline) complexes. Angew Chem Int Ed Engl. 2009;48(18):3326-8. doi: 10.1002/anie.200806080.
7. Lin L, Chen Z, Yang X, Liu X, Feng X: Efficient enantioselective hetero-Diels-Alder reaction of Brassard's diene with aliphatic aldehydes: a one-step synthesis of (R)-(+)-kavain and (S)-(+)-dihydrokavain. Org Lett. 2008 Mar 20;10(6):1311-4. doi: 10.1021/ol8002282. Epub 2008 Feb 28.
8. Du H, Zhao D, Ding K: Enantioselective catalysis of the hetero-Diels-Alder reaction between Brassard's diene and aldehydes by hydrogen-bonding activation: a one-step synthesis of (S)-(+)-dihydrokawain. Chemistry. 2004 Nov 19;10(23):5964-70.
9. Herath W, Ferreira D, Mikell JR, Khan IA: Microbial metabolism. Part 5. Dihydrokawain. Chem Pharm Bull (Tokyo). 2004 Nov;52(11):1372-4.
10. Uebelhack R, Franke L, Schewe HJ: Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava). Pharmacopsychiatry. 1998 Sep;31(5):187-92.
11. Jamieson DD, Duffield PH: The antinociceptive actions of kava components in mice. Clin Exp Pharmacol Physiol. 1990 Jul;17(7):495-507.
12. Bobeldijk I, Boonzaaijer G, Spies-Faber EJ, Vaes WH: Determination of kava lactones in food supplements by liquid chromatography-atmospheric pressure chemical ionisation tandem mass spectrometry. J Chromatogr A. 2005 Mar 4;1067(1-2):107-14.
13. Li Y, Mei H, Wu Q, Zhang S, Fang JL, Shi L, Guo L: Methysticin and 7,8-dihydromethysticin are two major kavalactones in kava extract to induce CYP1A1. Toxicol Sci. 2011 Dec;124(2):388-99. doi: 10.1093/toxsci/kfr235. Epub 2011 Sep 9.
14. Wu D, Yu L, Nair MG, DeWitt DL, Ramsewak RS: Cyclooxygenase enzyme inhibitory compounds with antioxidant activities from Piper methysticum (kava kava) roots. Phytomedicine. 2002 Jan;9(1):41-7.
15. Folmer F, Blasius R, Morceau F, Tabudravu J, Dicato M, Jaspars M, Diederich M: Inhibition of TNFalpha-induced activation of nuclear factor kappaB by kava (Piper methysticum) derivatives. Biochem Pharmacol. 2006 Apr 14;71(8):1206-18. Epub 2006 Feb 7.
16. Baum SS, Hill R, Rommelspacher H: Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Prog Neuropsychopharmacol Biol Psychiatry. 1998 Oct;22(7):1105-20.
17. Otoguro K, Iwatsuki M, Ishiyama A, Namatame M, Nishihara-Tsukashima A, Kiyohara H, Hashimoto T, Asakawa Y, Omura S, Yamada H: In vitro antitrypanosomal activity of some phenolic compounds from propolis and lactones from Fijian Kawa (Piper methysticum). J Nat Med. 2012 Jul;66(3):558-61. doi: 10.1007/s11418-011-0613-z. Epub 2011 Nov 25.
18. Ma Y, Sachdeva K, Liu J, Ford M, Yang D, Khan IA, Chichester CO, Yan B: Desmethoxyyangonin and dihydromethysticin are two major pharmacological kavalactones with marked activity on the induction of CYP3A23. Drug Metab Dispos. 2004 Nov;32(11):1317-24. Epub 2004 Jul 28.
19. Hashimoto T, Suganuma M, Fujiki H, Yamada M, Kohno T, Asakawa Y: Isolation and synthesis of TNF-alpha release inhibitors from Fijian kawa (Piper methysticum). Phytomedicine. 2003 May;10(4):309-17.
20. Feltenstein MW, Lambdin LC, Ganzera M, Ranjith H, Dharmaratne W, Nanayakkara NP, Khan IA, Sufka KJ: Anxiolytic properties of Piper methysticum extract samples and fractions in the chick social-separation-stress procedure. Phytother Res. 2003 Mar;17(3):210-6.
21. Xuan TD, Elzaawely AA, Fukuta M, Tawata S: Herbicidal and Fungicidal Activities of Lactones in Kava (Piper methysticum). J Agric Food Chem. 2006 Feb 8;54(3):720-5.
22. Arai Y, Masuda T, Yoneda S, Masaki Y, Shiro M: Asymmetric synthesis of (+)-dihydrokawain-5-ol. J Org Chem. 2000 Jan 14;65(1):258-62.
23. Yuan CS, Dey L, Wang A, Mehendale S, Xie JT, Aung HH, Ang-Lee MK: Kavalactones and dihydrokavain modulate GABAergic activity in a rat gastric-brainstem preparation. Planta Med. 2002 Dec;68(12):1092-6.
24. Teschke R, Lebot V: Proposal for a kava quality standardization code. Food Chem Toxicol. 2011 Oct;49(10):2503-16. doi: 10.1016/j.fct.2011.06.075. Epub 2011 Jul 3.
25. Xuan TD, Chung IM, Khanh TD, Tawata S: Identification of phytotoxic substances from early growth of barnyard grass (Echinochloa crusgalli) root exudates. J Chem Ecol. 2006 Apr;32(4):895-906. Epub 2006 May 5.
26. Whittaker P, Clarke JJ, San RH, Betz JM, Seifried HE, de Jager LS, Dunkel VC: Evaluation of commercial kava extracts and kavalactone standards for mutagenicity and toxicity using the mammalian cell gene mutation assay in L5178Y mouse lymphoma cells. Food Chem Toxicol. 2008 Jan;46(1):168-74. Epub 2007 Jul 31.
27. Keledjian J, Duffield PH, Jamieson DD, Lidgard RO, Duffield AM: Uptake into mouse brain of four compounds present in the psychoactive beverage kava. J Pharm Sci. 1988 Dec;77(12):1003-6.
28. Pescitelli G, Bilia AR, Bergonzi MC, Vincieri FF, Di Bari L: Cyclodextrins as carriers for kavalactones in aqueous media: spectroscopic characterization of (S)-7,8-dihydrokavain and beta-cyclodextrin inclusion complex. J Pharm Biomed Anal. 2010 Aug 1;52(4):479-83. doi: 10.1016/j.jpba.2010.01.037. Epub 2010 Feb 1.
29. Rasmussen AK, Scheline RR, Solheim E, Hansel R: Metabolism of some kava pyrones in the rat. Xenobiotica. 1979 Jan;9(1):1-16.
30. Warburton E, Bristow T: Fourier transform ion cyclotron resonance mass spectrometry for the characterisation of kavalactones in the kava plant: elemental formulae confirmation by dual spray accurate mass measurement and structural confirmation by infrared multiphoton dissociation and sustained off-resonance irradiation collision induced dissociation. Eur J Mass Spectrom (Chichester). 2006;12(4):223-33.
31. Tarbah F, Mahler H, Kardel B, Weinmann W, Hafner D, Daldrup T: Kinetics of kavain and its metabolites after oral application. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jun 5;789(1):115-30.
32. Haberlein H, Boonen G, Beck MA: Piper methysticum: enantiomeric separation of kavapyrones by high performance liquid chromatography. Planta Med. 1997 Feb;63(1):63-5.
33. Johnson BM, Qiu SX, Zhang S, Zhang F, Burdette JE, Yu L, Bolton JL, van Breemen RB: Identification of novel electrophilic metabolites of piper methysticum Forst (Kava). Chem Res Toxicol. 2003 Jun;16(6):733-40.
34. Singh RP, Singh VK: Facile one-step synthesis of beta-alkoxy lactone via sequential lactonization and 1,4-addition of alkoxide group: total synthesis of all stereoisomers of dihydrokawain-5-ol. J Org Chem. 2004 May 14;69(10):3425-30.
35. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.