Perrottetinene

Perrottetinene
Clinical data
ATC code	none;
Legal status
Legal status	BR: List F2; CA: Schedule II;
Identifiers
	IUPAC name (6aS,10aR)- 6,6,9-trimethyl- 3-(2-phenylethyl)- 6a,7,8,10a-tetrahydrobenzo[c]chromen- 1-ol;
CAS Number	160041-34-9 ;
PubChem CID	24766094;
ChemSpider	28284856;
CompTox Dashboard (EPA)	DTXSID401028205 ;
Chemical and physical data
Formula	C24H28O2
Molar mass	348.486 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=C[C@H]2c3c(cc(cc3OC([C@H]2CC1)(C)C)CCc4ccccc4)O;
	InChI InChI=1S/C24H28O2/c1-16-9-12-20-19(13-16)23-21(25)14-18(15-22(23)26-24(20,2)3)11-10-17-7-5-4-6-8-17/h4-8,13-15,19-20,25H,9-12H2,1-3H3/t19-,20+/m1/s1; Key:DYHMKBLKWFFFSZ-UXHICEINSA-N;
	(verify)

Perrottetinene is a naturally occurring cannabinoid compound found in liverworts from the genus Radula native to Japan, New Zealand and Costa Rica, namely Radula perrottetii, Radula marginata and Radula laxiramea,^[1]^[2] along with a number of similar compounds.^[3]^[4] Its chemical structure closely resembles that of THC, the main active component of marijuana but with a cis rather than trans conformation and a bibenzyl tailchain instead of pentyl.^[5] The absolute configuration of perrottetinene was established in 2008 by an enantioselective total synthesis.^[6]

Pharmacology

In 2018, a study showed that perrottetinene is mild to moderately psychoactive through activation of the cannabinoid receptor 1. (-)-cis-PET was found to have a binding affinity of 481nM at CB1 and 225nM at CB2 while the unnatural (-)-trans-PET was found to have a binding affinity of 127nM at CB1 and 126nM at CB2, both acting as partial agonists. In terms of binding affinity this study found cis-PET to be over 22x weaker than Delta-9-THC. The same study also reported significantly reduced prostaglandin D2 and E2 brain concentrations in mice after perrottetinene administration.^[7]

Perrottetinene is structurally related to machaeriol A and other machaeriols found in Machaerium species.^[8]

References

^ Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (1999-04-01). "Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension". Pulmonary Circulation. 10 (1): 147–150. doi:10.1515/znc-1999-3-401. PMC 7052475. PMID 32166015.
^ Kumar A, Premoli M, Aria F, Bonini SA, Maccarinelli G, Gianoncelli A, et al. (June 2019). "Cannabimimetic plants: are they new cannabinoidergic modulators?". Planta. 249 (6): 1681–1694. doi:10.1007/s00425-019-03138-x. PMID 30877436. S2CID 253886986.
^ Toyota M, Kinugawa T, Asakawa Y (1994). "Bibenzyl cannabinoid and bisbibenzyl derivative from the liverwort Radula perrottetii". Phytochemistry. 37 (3): 859–862. doi:10.1016/S0031-9422(00)90371-6.
^ Toyota M, Shimamura T, Ishii H, Renner M, Braggins J, Asakawa Y (October 2002). "New bibenzyl cannabinoid from the New Zealand liverwort Radula marginata". Chemical & Pharmaceutical Bulletin. 50 (10): 1390–1392. doi:10.1248/cpb.50.1390. PMID 12372871.
^ Reis MH, Antunes D, Santos LH, Guimarães AC, Caffarena ER (December 2020). "Shared Binding Mode of Perrottetinene and Tetrahydrocannabinol Diastereomers inside the CB1 Receptor May Incentivize Novel Medicinal Drug Design: Findings from an in Silico Assay". ACS Chemical Neuroscience. 11 (24): 4289–4300. doi:10.1021/acschemneuro.0c00547. PMID 33201672. S2CID 227038959.
^ Song Y, Hwang S, Gong P, Kim D, Kim S (January 2008). "Stereoselective total synthesis of (-)-perrottetinene and assignment of its absolute configuration". Organic Letters. 10 (2): 269–271. doi:10.1021/ol702692q. PMID 18085788.
^ Chicca A, Schafroth MA, Reynoso-Moreno I, Erni R, Petrucci V, Carreira EM, Gertsch J (October 2018). "Uncovering the psychoactivity of a cannabinoid from liverworts associated with HAVOK". Science Advances. 4 (10): eaat2166. Bibcode:2018SciA....4.2166C. doi:10.1126/sciadv.aat2166. PMC 6200358. PMID 30397641.
^ "Machaeriol A".

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[1] Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, et al. (1999-04-01). "Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension". Pulmonary Circulation. 10 (1): 147–150. doi:10.1515/znc-1999-3-401. PMC 7052475. PMID 32166015.

[pmid30877436-2] Kumar A, Premoli M, Aria F, Bonini SA, Maccarinelli G, Gianoncelli A, et al. (June 2019). "Cannabimimetic plants: are they new cannabinoidergic modulators?". Planta. 249 (6): 1681–1694. doi:10.1007/s00425-019-03138-x. PMID 30877436. S2CID 253886986.

[3] Toyota M, Kinugawa T, Asakawa Y (1994). "Bibenzyl cannabinoid and bisbibenzyl derivative from the liverwort Radula perrottetii". Phytochemistry. 37 (3): 859–862. doi:10.1016/S0031-9422(00)90371-6.

[4] Toyota M, Shimamura T, Ishii H, Renner M, Braggins J, Asakawa Y (October 2002). "New bibenzyl cannabinoid from the New Zealand liverwort Radula marginata". Chemical & Pharmaceutical Bulletin. 50 (10): 1390–1392. doi:10.1248/cpb.50.1390. PMID 12372871.

[pmid33201672-5] Reis MH, Antunes D, Santos LH, Guimarães AC, Caffarena ER (December 2020). "Shared Binding Mode of Perrottetinene and Tetrahydrocannabinol Diastereomers inside the CB1 Receptor May Incentivize Novel Medicinal Drug Design: Findings from an in Silico Assay". ACS Chemical Neuroscience. 11 (24): 4289–4300. doi:10.1021/acschemneuro.0c00547. PMID 33201672. S2CID 227038959.

[6] Song Y, Hwang S, Gong P, Kim D, Kim S (January 2008). "Stereoselective total synthesis of (-)-perrottetinene and assignment of its absolute configuration". Organic Letters. 10 (2): 269–271. doi:10.1021/ol702692q. PMID 18085788.

[7] Chicca A, Schafroth MA, Reynoso-Moreno I, Erni R, Petrucci V, Carreira EM, Gertsch J (October 2018). "Uncovering the psychoactivity of a cannabinoid from liverworts associated with HAVOK". Science Advances. 4 (10): eaat2166. Bibcode:2018SciA....4.2166C. doi:10.1126/sciadv.aat2166. PMC 6200358. PMID 30397641.

[8] "Machaeriol A".

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Pharmacology

See also

References