Showing Compound Card for Delta-9-tetrahydrocannabinolic acid A (CDB000016)

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Record Information
Version1.0
Created at2020-03-19 00:35:33 UTC
Updated at2020-11-18 16:35:09 UTC
CannabisDB IDCDB000016
Secondary Accession NumbersNot Available
Cannabis Compound Identification
Common NameDelta-9-tetrahydrocannabinolic acid A
DescriptionDelta-9-Tetrahydrocannabinolic acid A or THC acid A is classified as a delta-9-tetrahydrocannabinol, one of the major non-psychoactive cannabinoid compounds that are found only in the cannabis plant. THC acid A, and to a much lesser extent THC acid B, are biosynthetic precursors to delta-9-tetrahydrocannabinol (delta-9-THC), the principal psychoactive constituent of the cannabis plant. The difference between THC acid A and B is the position of the carboxyl functional group. In THC acid A, it is on the C-2 whereas in THC acid B, it is on the C-4 (PMID: 6991645 ). THC acid is produced via the following pathway: Geranyl pyrophosphate and olivetolic acid react, catalyzed by an enzyme Geranyl-pyrophosphate—olivetolic acid geranyltransferase to produce cannabigerolic acid which is then cyclized by the enzyme THC acid synthase to give THC acid. Over time, or when heated (via vaping or smoking), THC acid is decarboxylated, producing THC. While smoking a joint or baking cookies, THC acid A is partially converted into the psychoactive delta-9-THC via decarboxylation. Therefore, THC acid A is incorporated to a certain extent by cannabis consumers and is a promising candidate for use as an additional consumption marker (PMID: 22921834 ). While some studies showed that delta-9-THC acid binds cannabinoid type one (CB1) receptors with a Ki value of 23.5 nM (PMID: 25311884 ), others had found negligible activity (PMID: 18303850 ). Decarboxylation of THC acid A to THC during storage or under certain experimental conditions may contribute to these contrasting results. A recent study using freshly prepared and highly pure delta-9-THC acid (98%) showed that it yet had a low binding affinity for CB1 and CB2 receptors (PMID: 28861508 ), strongly suggesting that delta-9-THC acid biological activities are not mediated by interaction with these receptors. However, in another study, Delta-9-THC acid exhibited anti-emetic and immune-modulatory activities through CB1-dependent and CB1-in- dependent mechanisms, respectively (PMID: 16504929 ; PMID: 23889598 ). Delta-9-THC acid showed potent neuroprotective activity and may aid in the treatment of Huntington's disease and possibly other neurodegenerative and neuroinflammatory diseases (PMID: 28853159 ).
Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
ValueSource
9-Carboxy-delta(9)-THCChEBI
9-Carboxy-THCChEBI
9-Carboxy-δ(9)-THCGenerator
delta(9)-TetrahydrocannabinolateGenerator
Δ(9)-tetrahydrocannabinolateGenerator
Δ(9)-tetrahydrocannabinolic acidGenerator
THC-9-COOHMeSH
THCA-a compoundMeSH
Chemical FormulaC22H30O4
Average Molecular Weight358.48
Monoisotopic Molecular Weight358.2144
IUPAC Name(6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-pentyl-6H,6aH,7H,8H,10aH-benzo[c]isochromene-2-carboxylic acid
Traditional Name(6aR,10aR)-1-hydroxy-6,6,9-trimethyl-3-pentyl-6aH,7H,8H,10aH-benzo[c]isochromene-2-carboxylic acid
CAS Registry Number23978-85-0
SMILES
CCCCCC1=C(C(O)=O)C(O)=C2[C@@H]3C=C(C)CC[C@H]3C(C)(C)OC2=C1
InChI Identifier
InChI=1S/C22H30O4/c1-5-6-7-8-14-12-17-19(20(23)18(14)21(24)25)15-11-13(2)9-10-16(15)22(3,4)26-17/h11-12,15-16,23H,5-10H2,1-4H3,(H,24,25)/t15-,16-/m1/s1
InChI KeyUCONUSSAWGCZMV-HZPDHXFCSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as 2,2-dimethyl-1-benzopyrans. These are organic compounds containing a 1-benzopyran moiety that carries two methyl groups at the 2-position.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzopyrans
Sub Class1-benzopyrans
Direct Parent2,2-dimethyl-1-benzopyrans
Alternative Parents
Substituents
  • 2,2-dimethyl-1-benzopyran
  • Hydroxybenzoic acid
  • Salicylic acid or derivatives
  • 1-hydroxy-4-unsubstituted benzenoid
  • Alkyl aryl ether
  • Benzenoid
  • Vinylogous acid
  • Carboxylic acid derivative
  • Carboxylic acid
  • Ether
  • Monocarboxylic acid or derivatives
  • Oxacycle
  • Organic oxide
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Not Available
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
logPNot AvailableNot Available
Predicted Properties
PropertyValueSource
logP5.13ALOGPS
logP6.25ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)2.89ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.76 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity103.99 m³·mol⁻¹ChemAxon
Polarizability41.91 ųChemAxon
Number of Rings3ChemAxon
BioavailabilityYesChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
EI-MS/GC-MS
TypeDescriptionSplash KeyView
Predicted GC-MSDelta-9-tetrahydrocannabinolic acid A, 1 TMS, Predicted GC-MS Spectrum - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSDelta-9-tetrahydrocannabinolic acid A, 1 TMS, Predicted GC-MS Spectrum - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSDelta-9-tetrahydrocannabinolic acid A, 2 TMS, Predicted GC-MS Spectrum - 70eV, PositiveNot AvailableSpectrum
MS/MS
TypeDescriptionSplash KeyView
Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available2020-06-30View Spectrum
Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available2020-06-30View Spectrum
NMRNot Available
Pathways
Pathways
Protein Targets
EnzymesNot Available
TransportersNot Available
Metal BindingsNot Available
Receptors
Protein NameGene NameLocusUniprot IDDetails
Cannabinoid receptor 1CNR16q14-q15P21554 details
Cannabinoid receptor 2CNR21p36.11P34972 details
Transcriptional FactorsNot Available
Concentrations Data
Cannabis CultivarStatusValueReferenceDetails
Alien DawgDetected and Quantified206.0 mg/g dry wt
    • David S. Wishart,...
 details
GabriolaDetected and Quantified187.0 mg/g dry wt
    • David S. Wishart,...
 details
Island HoneyDetected and Quantified194.0 mg/g dry wt
    • David S. Wishart,...
 details
QuadraDetected and Quantified194.0 mg/g dry wt
    • David S. Wishart,...
 details
Sensi StarDetected and Quantified218.0 mg/g dry wt
    • David S. Wishart,...
 details
Tangerine DreamDetected and Quantified115.0 mg/g dry wt
    • David S. Wishart,...
 details
HMDB IDNot Available
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDCPD-7169
BiGG IDNot Available
Wikipedia LinkNot Available
METLIN IDNot Available
PubChem Compound98523
PDB IDNot Available
ChEBI ID67078
References
General References
  1. Turner CE, Elsohly MA, Boeren EG: Constituents of Cannabis sativa L. XVII. A review of the natural constituents. J Nat Prod. 1980 Mar-Apr;43(2):169-234. doi: 10.1021/np50008a001. [PubMed:6991645 ]
  2. Roth N, Wohlfarth A, Muller M, Auwarter V: Regioselective synthesis of isotopically labeled Delta9-tetrahydrocannabinolic acid A (THCA-A-D3) by reaction of Delta9-tetrahydrocannabinol-D3 with magnesium methyl carbonate. Forensic Sci Int. 2012 Oct 10;222(1-3):368-72. doi: 10.1016/j.forsciint.2012.07.019. Epub 2012 Aug 23. [PubMed:22921834 ]
  3. Rosenthaler S, Pohn B, Kolmanz C, Huu CN, Krewenka C, Huber A, Kranner B, Rausch WD, Moldzio R: Differences in receptor binding affinity of several phytocannabinoids do not explain their effects on neural cell cultures. Neurotoxicol Teratol. 2014 Nov-Dec;46:49-56. doi: 10.1016/j.ntt.2014.09.003. Epub 2014 Oct 12. [PubMed:25311884 ]
  4. Ahmed SA, Ross SA, Slade D, Radwan MM, Zulfiqar F, Matsumoto RR, Xu YT, Viard E, Speth RC, Karamyan VT, ElSohly MA: Cannabinoid ester constituents from high-potency Cannabis sativa. J Nat Prod. 2008 Apr;71(4):536-42. doi: 10.1021/np070454a. Epub 2008 Feb 28. [PubMed:18303850 ]
  5. McPartland JM, MacDonald C, Young M, Grant PS, Furkert DP, Glass M: Affinity and Efficacy Studies of Tetrahydrocannabinolic Acid A at Cannabinoid Receptor Types One and Two. Cannabis Cannabinoid Res. 2017 May 1;2(1):87-95. doi: 10.1089/can.2016.0032. eCollection 2017. [PubMed:28861508 ]
  6. Verhoeckx KC, Korthout HA, van Meeteren-Kreikamp AP, Ehlert KA, Wang M, van der Greef J, Rodenburg RJ, Witkamp RF: Unheated Cannabis sativa extracts and its major compound THC-acid have potential immuno-modulating properties not mediated by CB1 and CB2 receptor coupled pathways. Int Immunopharmacol. 2006 Apr;6(4):656-65. doi: 10.1016/j.intimp.2005.10.002. Epub 2005 Nov 7. [PubMed:16504929 ]
  7. Rock EM, Kopstick RL, Limebeer CL, Parker LA: Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus. Br J Pharmacol. 2013 Oct;170(3):641-8. doi: 10.1111/bph.12316. [PubMed:23889598 ]
  8. Nadal X, Del Rio C, Casano S, Palomares B, Ferreiro-Vera C, Navarrete C, Sanchez-Carnerero C, Cantarero I, Bellido ML, Meyer S, Morello G, Appendino G, Munoz E: Tetrahydrocannabinolic acid is a potent PPARgamma agonist with neuroprotective activity. Br J Pharmacol. 2017 Dec;174(23):4263-4276. doi: 10.1111/bph.14019. Epub 2017 Nov 2. [PubMed:28853159 ]
  9. Hunter JE, Zhang J, Kris-Etherton PM: Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review. Am J Clin Nutr. 2010 Jan;91(1):46-63. doi: 10.3945/ajcn.2009.27661. Epub 2009 Nov 25. [PubMed:19939984 ]