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 family Radulaceae native to Japan, New Zealand and Costa Rica, namely Cladoradula 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-Perrottetinene was found to have a binding affinity of 481 nM at CB1 and 225 nM at CB2, while the unnatural (-)-trans-perrottetinene was found to more active with binding affinities of 127 nM at CB1 and 126 nM at CB2, both acting as partial agonists. In terms of binding affinity, this study found cis-perrottetinene to be over 22 times 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