Tetrahydrocannabiphorol: Difference between revisions

Tetrahydrocannabiphorol
Clinical data
Other names	(-)-Trans-Δ9-tetrahydrocannabiphorol; Δ9-THCP; (C7)-Δ9-THC; THC-Heptyl
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;

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Revision as of 15:37, 21 October 2023

Tetrahydrocannabiphorol (THCP) is a potent phytocannabinoid, a CB₁ and CB₂ agonist which was known as a synthetic homologue of THC,^[1] but for the first time in 2019 was isolated as a natural product in trace amounts from Cannabis sativa.^[2]^[3] It 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 1.2nM at CB1, approximately 33 times that of Delta-9-THC (40nM at CB1).^[4]

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.^[5]

Delta-8-THCP

The Δ⁸ isomer is also known as a synthetic cannabinoid under the code name JWH-091.^[6]^[7] It's unconfirmed whether or not Delta-8-THCP is found naturally in cannabis plants, but likely is due to Delta-8-THC itself being a degraded form of Delta-9-THC. ^[8] JWH-091 has approximately double the binding affinity at the CB1 receptor (22nM ± 3.9nM) in comparison to Delta-9-THC (40.7nM ± 1.7nM) or Delta-8-THC (44nM ± 12nM),^[7] but appears significantly lower in vitro than the binding activity of Delta-9-THCP (Ki = 1.2 nM CB1)^[4]

Natural occurrence in Cannabis

Delta-9-THCP occurs naturally in Cannabis but in small amounts, an analysis on mid to high THC strains ranged approximately from 0.0023% to 0.0136% (w/w) (approximately 0.02mg-0.13mg per gram) with no correlation with THC percentage, such a strain with 8% THC vs 20% THC both with similar amounts of THCP.^[2]

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, Justin; Greenbaum, Eric A. (26 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, Cinzia; Linciano, Pasquale; Russo, Fabiana; Luongo, Livio; Iannotta, Monica; Maione, Sabatino; Laganà, Aldo; Capriotti, Anna Laura; Forni, Flavio; Vandelli, Maria Angela; Gigli, Giuseppe; Cannazza, Giuseppe (30 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. doi:10.1038/s41598-019-56785-1. PMC 6937300. PMID 31889124.
^ 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, Arno; Fischedick, Justin T.; Díez, Mónica Llano; Lubbe, Andrea; Ruhaak, Renee L. (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.

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[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, Justin; Greenbaum, Eric A. (26 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, Cinzia; Linciano, Pasquale; Russo, Fabiana; Luongo, Livio; Iannotta, Monica; Maione, Sabatino; Laganà, Aldo; Capriotti, Anna Laura; Forni, Flavio; Vandelli, Maria Angela; Gigli, Giuseppe; Cannazza, Giuseppe (30 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. doi:10.1038/s41598-019-56785-1. PMC 6937300. PMID 31889124.

[5] 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.

[pmid10454479-6] 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_2016-7] 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.

[8] Hazekamp, Arno; Fischedick, Justin T.; Díez, Mónica Llano; Lubbe, Andrea; Ruhaak, Renee L. (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.

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@@ Line 47: / Line 47: @@
 {{clear-left}}
-The Δ<sup>8</sup> isomer is also known as a [[synthetic cannabinoid]] under the code name '''JWH-091'''.<ref name="pmid10454479">{{cite journal | vauthors = Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, Saha B, Razdan RK | display-authors = 6 | title = Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 290 | issue = 3 | pages = 1065–1079 | date = September 1999 | pmid = 10454479 | url = https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10454479 }}</ref><ref name="Bow_2016">{{cite journal | vauthors = Bow EW, Rimoldi JM | title = The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation | journal = Perspectives in Medicinal Chemistry | volume = 8 | issue =  | pages = 17–39 | date = 2016 | pmid = 27398024 | pmc = 4927043 | doi = 10.4137/PMC.S32171 }}</ref> It's unconfirmed whether or not Delta-8-THCP is found naturally in cannabis plants, but likely is due to Delta-8-THC itself being a degraded form of Delta-9-THC. <ref>{{cite book |doi=10.1016/B978-008045382-8.00091-5 |chapter=Chemistry of Cannabis |title=Comprehensive Natural Products II |date=2010 |last1=Hazekamp |first1=Arno |last2=Fischedick |first2=Justin T. |last3=Díez |first3=Mónica Llano |last4=Lubbe |first4=Andrea |last5=Ruhaak |first5=Renee L. |pages=1033–1084 |isbn=9780080453828 }}</ref> JWH-091 has approximately double the binding affinity at the CB1 receptor (22nM ± 3.9nM) in comparison to Delta-9-THC (40.7nM ± 1.7nM) or Delta-8-THC (44nM ± 12nM),<ref name="Bow_2016" /> but appears significantly lower in vitro than the binding activity of Delta-9-THCP (Ki = 1.2 nM CB1)<ref name="Citti et al 2019"/>
+The Δ<sup>8</sup> isomer is also known as a [[synthetic cannabinoid]] under the code name '''JWH-091'''.<ref name="pmid10454479">{{cite journal | vauthors = Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, Saha B, Razdan RK | display-authors = 6 | title = Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 290 | issue = 3 | pages = 1065–1079 | date = September 1999 | pmid = 10454479 | url = https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10454479 }}</ref><ref name="Bow_2016">{{cite journal | vauthors = Bow EW, Rimoldi JM | title = The Structure-Function Relationships of Classical Cannabinoids: CB1/CB2 Modulation | journal = Perspectives in Medicinal Chemistry | volume = 8 | issue =  | pages = 17–39 | date = 2016 | pmid = 27398024 | pmc = 4927043 | doi = 10.4137/PMC.S32171 }}</ref> It's unconfirmed whether or not Delta-8-THCP is found naturally in cannabis plants, but likely is due to Delta-8-THC itself being a degraded form of Delta-9-THC. <ref>{{cite book |doi=10.1016/B978-008045382-8.00091-5 |chapter=Chemistry of Cannabis |title=Comprehensive Natural Products II |date=2010 |last1=Hazekamp |first1=Arno |last2=Fischedick |first2=Justin T. |last3=Díez |first3=Mónica Llano |last4=Lubbe |first4=Andrea |last5=Ruhaak |first5=Renee L. |pages=1033–1084 |isbn=978-0-08-045382-8 }}</ref> JWH-091 has approximately double the binding affinity at the CB1 receptor (22nM ± 3.9nM) in comparison to Delta-9-THC (40.7nM ± 1.7nM) or Delta-8-THC (44nM ± 12nM),<ref name="Bow_2016" /> but appears significantly lower in vitro than the binding activity of Delta-9-THCP (Ki = 1.2 nM CB1)<ref name="Citti et al 2019"/>
 == Natural occurrence in Cannabis ==