Tetrahydrocannabiphorol

Tetrahydrocannabiphorol
Clinical data
Pronunciation	/tɛtʃrəhaɪʒroʊkənæbɪfoʊrɔːl/
Other names	(-)-Trans-Δ9-tetrahydrocannabiphorol,; Δ9-THCP,; (C7)-Δ9-THC,; THC-Heptyl
Drug class	Cannabinoid
Identifiers
	IUPAC name (6aR,10aR)-3-heptyl-6,6,9-trimethyl-6a,7,8,10a-tetrahydrobenzo[c]chromen-1-ol;
CAS Number	54763-99-4;
PubChem CID	6453074;
ChemSpider	4955468;
CompTox Dashboard (EPA)	DTXSID70203228 ;
Chemical and physical data
Formula	C23H34O2
Molar mass	342.523 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CCCCCCCc3cc2OC(C)(C)[C@@H]1CCC(C)=C[C@H]1c2c(O)c3;
	InChI InChI=1S/C23H34O2/c1-5-6-7-8-9-10-17-14-20(24)22-18-13-16(2)11-12-19(18)23(3,4)25-21(22)15-17/h13-15,18-19,24H,5-12H2,1-4H3/t18-,19-/m1/s1; Key:OJTMRZHYTZMJKX-RTBURBONSA-N;

Tetrahydrocannabiphorol (THCP) is a potent phytocannabinoid, a CB₁ and CB₂ receptor agonist which was known as a synthetic homologue of tetrahydrocannabinol (THC),^[1] but for the first time in 2019 was isolated as a natural product in trace amounts from Cannabis sativa.^[2]^[3]

THCP is structurally similar to Δ⁹-THC, the main active component of cannabis, but with the pentyl side chain extended to heptyl. Since it has a longer side chain, its cannabinoid effects are "far higher than Δ⁹-THC itself." Tetrahydrocannabiphorol has a reported binding affinity of 1.2 nM at CB₁, approximately 33 times that of Δ⁹-THC (40 nM at CB₁).^[4]

THCP was studied by Roger Adams as early as 1942.^[5]

Isomers

Delta-3-THCP

The Δ³/Δ^6a(10a) isomer Δ³-THCP was synthesised in 1941, and was found to have around the same potency as Δ³-THC, unlike the hexyl homologue parahexyl which was significantly stronger.^[6]

Delta-8-THCP

The Δ⁸ isomer is also known as a synthetic cannabinoid under the code name JWH-091.^[7]^[8] It's unconfirmed whether or not Δ⁸-THCP is found naturally in cannabis plants, but likely is due to Δ⁸-THC itself being a degraded form of Δ⁹-THC.^[9] JWH-091 has approximately double the binding affinity at the CB₁ receptor (22 nM ± 3.9 nM) in comparison to Δ⁹-THC (40.7 nM ± 1.7 nM) or Δ⁸-THC (44 nM ± 12 nM),^[8] but appears significantly lower in vitro than the binding activity of Δ⁹-THCP (K_i = 1.2 nM)^[4]

Natural cannabis occurrence

The Δ⁹ isomer of THCP occurs naturally in cannabis, but in small amounts. A 2021 study reported the content of Δ⁹-THCP ranging from 0.0023% to 0.0136% (w/w) (approximately 0.02–0.13 mg/g) without correlation to THC percentage in Δ⁹-THC-dominant strains of cannabis; that study failed to detect THCP in CBD-dominant strains.^[2]^[10]

References

^ Harvey DJ (March 1985). "Identification of hepatic metabolites of n-heptyl-delta-1-tetrahydrocannabinol in the mouse". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 15 (3): 187–197. doi:10.3109/00498258509045349. PMID 2992174.
^ ^a ^b Bueno J, Greenbaum EA (February 2021). "(-)-trans-Δ⁹-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes". Journal of Natural Products. 84 (2): 531–536. doi:10.1021/acs.jnatprod.0c01034. PMID 33565878. S2CID 231866062.
^ Linciano P, Russo F, Citti C, Tolomeo F, Paris R, Fulvio F, et al. (December 2021). "The novel heptyl phorolic acid cannabinoids content in different Cannabis sativa L. accessions". Talanta. 235: 122704. doi:10.1016/j.talanta.2021.122704. hdl:11380/1250339. PMID 34517579.
^ ^a ^b Citti C, Linciano P, Russo F, Luongo L, Iannotta M, Maione S, et al. (December 2019). "A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ⁹-tetrahydrocannabinol: Δ⁹-Tetrahydrocannabiphorol". Scientific Reports. 9 (1): 20335. Bibcode:2019NatSR...920335C. doi:10.1038/s41598-019-56785-1. PMC 6937300. PMID 31889124.
^ Adams R, Loewe S, Smith CM, McPhee WD (1942). "Tetrahydrocannabinol Homologs and Analogs with Marihuana Activity. XIII¹". Journal of the American Chemical Society. 64 (3): 694–697. doi:10.1021/ja01255a061.
^ Adams R, Loewe S, Jelinek C, Wolff H (July 1941). "Tetrahydrocannabinol Homologs with Marihuana Activity. IX". Journal of the American Chemical Society. 63 (7): 1971–1973. doi:10.1021/ja01852a052.
^ Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, et al. (September 1999). "Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists". The Journal of Pharmacology and Experimental Therapeutics. 290 (3): 1065–1079. PMID 10454479.
^ ^a ^b Bow EW, Rimoldi JM (2016). "The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation". Perspectives in Medicinal Chemistry. 8: 17–39. doi:10.4137/PMC.S32171. PMC 4927043. PMID 27398024.
^ Hazekamp A, Fischedick JT, Díez ML, Lubbe A, Ruhaak RL (2010). "Chemistry of Cannabis". Comprehensive Natural Products II. pp. 1033–1084. doi:10.1016/B978-008045382-8.00091-5. ISBN 978-0-08-045382-8.
^ Bueno J, Greenbaum EA (2021). "(-)- trans-Δ9-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes". Journal of Natural Products. 84 (2): 531–536. doi:10.1021/acs.jnatprod.0c01034. PMID 33565878. S2CID 231866062. Retrieved 19 Feb 2024.

[pmid2992174-1] Harvey DJ (March 1985). "Identification of hepatic metabolites of n-heptyl-delta-1-tetrahydrocannabinol in the mouse". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 15 (3): 187–197. doi:10.3109/00498258509045349. PMID 2992174.

[Bueno_Greenbaum_2021-2] Bueno J, Greenbaum EA (February 2021). "(-)-trans-Δ⁹-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes". Journal of Natural Products. 84 (2): 531–536. doi:10.1021/acs.jnatprod.0c01034. PMID 33565878. S2CID 231866062.

[3] Linciano P, Russo F, Citti C, Tolomeo F, Paris R, Fulvio F, et al. (December 2021). "The novel heptyl phorolic acid cannabinoids content in different Cannabis sativa L. accessions". Talanta. 235: 122704. doi:10.1016/j.talanta.2021.122704. hdl:11380/1250339. PMID 34517579.

[Citti_et_al_2019-4] Citti C, Linciano P, Russo F, Luongo L, Iannotta M, Maione S, et al. (December 2019). "A novel phytocannabinoid isolated from Cannabis sativa L. with an in vivo cannabimimetic activity higher than Δ⁹-tetrahydrocannabinol: Δ⁹-Tetrahydrocannabiphorol". Scientific Reports. 9 (1): 20335. Bibcode:2019NatSR...920335C. doi:10.1038/s41598-019-56785-1. PMC 6937300. PMID 31889124.

[5] Adams R, Loewe S, Smith CM, McPhee WD (1942). "Tetrahydrocannabinol Homologs and Analogs with Marihuana Activity. XIII¹". Journal of the American Chemical Society. 64 (3): 694–697. doi:10.1021/ja01255a061.

[6] Adams R, Loewe S, Jelinek C, Wolff H (July 1941). "Tetrahydrocannabinol Homologs with Marihuana Activity. IX". Journal of the American Chemical Society. 63 (7): 1971–1973. doi:10.1021/ja01852a052.

[pmid10454479-7] Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, et al. (September 1999). "Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists". The Journal of Pharmacology and Experimental Therapeutics. 290 (3): 1065–1079. PMID 10454479.

[Bow_2016-8] Bow EW, Rimoldi JM (2016). "The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation". Perspectives in Medicinal Chemistry. 8: 17–39. doi:10.4137/PMC.S32171. PMC 4927043. PMID 27398024.

[9] Hazekamp A, Fischedick JT, Díez ML, Lubbe A, Ruhaak RL (2010). "Chemistry of Cannabis". Comprehensive Natural Products II. pp. 1033–1084. doi:10.1016/B978-008045382-8.00091-5. ISBN 978-0-08-045382-8.

[10] Bueno J, Greenbaum EA (2021). "(-)- trans-Δ9-Tetrahydrocannabiphorol Content of Cannabis sativa Inflorescence from Various Chemotypes". Journal of Natural Products. 84 (2): 531–536. doi:10.1021/acs.jnatprod.0c01034. PMID 33565878. S2CID 231866062. Retrieved 19 Feb 2024.

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Isomers

Delta-3-THCP

Delta-8-THCP

Natural cannabis occurrence

See also

References