Collybolide

Collybolide is a chemical constituent of the Rhodocollybia maculata mushroom, a fungus that grows on rotting conifer wood. It is potentially a potent and selective K-opioid receptor agonist, like salvinorin A.[1] No total syntheses of this compound have been reported,[2] and research is inconclusive as to whether collybolide is a K-opioid receptor agonist, and it still remains unknown whether collybolide is a hallucinogen;[1] however, anecdotal reports suggest it is possible.

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
3D model (JSmol)
ChemSpider
  • 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
  • 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
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

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. K-opioid receptor agonists are under research for their potential in addiction treatment:[3] and 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.[4]

However, this is contested by 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, degradation during storage, or degradation during handling, produced a derivative of collybolide that is the true, but still unknown K-opioid receptor agonist.[5]

References
  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.
  2. Southgate, Emma Helen (2019-02-19). "Dearomative transformations in synthesis: I. Dearomative dihydroxylation with arenophiles II. Total synthesis of lycoricidine and narciclasine III. Towards the total synthesis of collybolide". hdl:2142/104966. {{cite journal}}: Cite journal requires |journal= (help)
  3. Santino, Federica; Gentilucci, Luca (January 2023). "Design of κ-Opioid Receptor Agonists for the Development of Potential Treatments of Pain with Reduced Side Effects". Molecules. 28 (1): 346. doi:10.3390/molecules28010346. ISSN 1420-3049. PMC 9822356. PMID 36615540.
  4. Chakraborty, Soumen; Majumdar, Susruta (2021-05-11). "Natural Products for the Treatment of Pain: Chemistry and Pharmacology of Salvinorin A, Mitragynine, and Collybolide". Biochemistry. 60 (18): 1381–1400. doi:10.1021/acs.biochem.0c00629. ISSN 0006-2960. PMC 7982354. PMID 32930582.
  5. 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.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.