Collybolide

Collybolide
Names
	Systematic IUPAC name (3S,4R,4aS,5R,8R,9aR)-4-(benzoyloxy)-3-(3-furanyl)hexahydro-5-methyl-5,8-Methano-1H-pyrano[3,4-d]oxepin-1,6(5H)-dione
	Other names (+)-Collybolide;
Identifiers
CAS Number	33340-30-6 ;
3D model (JSmol)	Interactive image; Interactive image;
ChemSpider	9627099;
PubChem CID	72966961;
	InChI InChI=1S/C22H20O7/c1-22-10-14(27-21(22)25)9-15-16(22)18(29-19(23)12-5-3-2-4-6-12)17(28-20(15)24)13-7-8-26-11-13/h2-8,11,14-18H,9-10H2,1H3/t14-,15-,16-,17+,18-,22-/m1/s1 Key: JLFUOYRQSZADHD-NVKOURDFSA-N; InChI=1S/C22H20O7/c1-22-10-14(27-21(22)25)9-15-16(22)18(29-19(23)12-5-3-2-4-6-12)17(28-20(15)24)13-7-8-26-11-13/h2-8,11,14-18H,9-10H2,1H3 Key: JLFUOYRQSZADHD-UHFFFAOYSA-N;
	SMILES O(C(=O)C1=CC=CC=C1)[C@@H]2[C@@]3([C@@]4(C)C[C@@H](C[C@]3(C(=O)O[C@]2(C=5C=COC5)[H])[H])OC4=O)[H]; CC12CC(C(C3C1C(C(OC3=O)C4=COC=C4)OC(=O)C5=CC=CC=C5))OC2=O;
Properties
Chemical formula	C22H20O7
Molar mass	396.395 g·mol−1
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Collybolide is a chemical constituent of the Rhodocollybia maculata mushroom, a fungus that grows on rotting conifer wood, which is potentially a potent and selective K-opioid receptor agonist, like salvinorin A.^[1] It is currently unknown if collybolide is a hallucinogen;^[1] however, anecdotal reports suggest it is possible.^{[citation needed]}

If it is active in humans, collybolide will be the only non-salvinorin selective K-opioid receptor agonist psychedelic.

Research

Gupta et al.^[1] found collybolide to exhibit biased K-opioid agonist activity. Along with an easily modifiable structure (in contrast to salvinorin A), collybolide has attracted attention for the development of next-generation K-opioid receptor agonist analgesics, antipruritics, and antidepressants. It is unknown if collybolide is a hallucinogen in humans.^[1]

However, this has been contested by a Shevick et al. who, after synthesizing collybolide, could not find K-opioid agonist activity of either enantiomer. Shevick et al. fault the 2016 assay and suggest an unidentified contaminant in the C. maculata extract; or that degradation during storage or handling produced a derivative of collybolide which is the true, but still unknown K-opioid receptor agonist.^[2]

References

^ ^a ^b ^c ^d Gupta, Achla; Gomes, Ivone; Bobeck, Erin N.; Fakira, Amanda K.; Massaro, Nicholas P.; Sharma, Indrajeet; Cavé, Adrien; Hamm, Heidi E.; Parello, Joseph; Devi, Lakshmi A. (9 May 2016). "Collybolide is a novel biased agonist of κ-opioid receptors with potent antipruritic activity". Proceedings of the National Academy of Sciences. 113 (21): 6041–6046. Bibcode:2016PNAS..113.6041G. doi:10.1073/pnas.1521825113. PMC 4889365. PMID 27162327.
^ Shevick, Sophia L.; Freeman, Stephan M.; Tong, Guanghu; Russo, Robin J.; Bohn, Laura M.; Shenvi, Ryan A. (27 July 2022). "Asymmetric Syntheses of (+)- and (−)-Collybolide Enable Reevaluation of kappa -Opioid Receptor Agonism". ACS Central Science. 8 (7): 948–954. doi:10.1021/acscentsci.2c00442. PMC 9335922. PMID 35912357.

[Gupta_Gomes_Bobeck_et_al_2016-1] Gupta, Achla; Gomes, Ivone; Bobeck, Erin N.; Fakira, Amanda K.; Massaro, Nicholas P.; Sharma, Indrajeet; Cavé, Adrien; Hamm, Heidi E.; Parello, Joseph; Devi, Lakshmi A. (9 May 2016). "Collybolide is a novel biased agonist of κ-opioid receptors with potent antipruritic activity". Proceedings of the National Academy of Sciences. 113 (21): 6041–6046. Bibcode:2016PNAS..113.6041G. doi:10.1073/pnas.1521825113. PMC 4889365. PMID 27162327.

[ShevickFreemanTong2022-2] Shevick, Sophia L.; Freeman, Stephan M.; Tong, Guanghu; Russo, Robin J.; Bohn, Laura M.; Shenvi, Ryan A. (27 July 2022). "Asymmetric Syntheses of (+)- and (−)-Collybolide Enable Reevaluation of kappa -Opioid Receptor Agonism". ACS Central Science. 8 (7): 948–954. doi:10.1021/acscentsci.2c00442. PMC 9335922. PMID 35912357.

[1]

[2]

Collybolide

Research

References

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