Chemistry:Elymoclavine

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Elymoclavine is an ergot alkaloid (ergoline alkaloid). It can be produced from C. fusiformis from Pennisetum typhoideum. It is a precursor in the biosynthesis of D-(+)-lysergic acid. Ergot alkaloids are natural products derived from L-tryptophan. They are often toxic for humans and animals. Despite that they are also well known for their pharmacological activities.[1][2]

The compound is described as being non-hallucinogenic in humans, instead producing mainly sedative effects, and as not contributing to the psychoactive or hallucinogenic effects of morning glory seeds.[3][4][5] The doses employed were not provided.[3][5]

Biosynthesis

The main building blocks for biosynthesis of elymoclavine are tryptophan (Trp) and DMAPP. DMATrp is obtained after electrophilic substitution followed by addition (Step A below). Then an amine is methylated by an N-methyltransfersase (Step B). Next, the allyl alcohol is oxidized to the diene (Step C). After 1,4-elimination, the diene undergoes an epoxidation (Step D). Then decarboxylation is followed by the 6-member ring formation and epoxide opened to form terminal alcohol (Step E). Obtained chanoclavine gets oxidized to chanoclavine aldehyde (Step F). Then the second 6-member ring forms and agroclavine is obtained after additional reductase (Steps G and H). Finally elymoclavine is generated after an oxidation (Step I). The last step is NADPH-dependent, and it is suggested that cytochrome P450 is the catalyst.[6][7]

File:Biosynthesis of elymoclavine.tif

References

  1. ↑ Ahimsa-Müller, M. A.; Markert A.; Hellwig S.; Knoop V.; Steiner U.; Drewke C.; Leistner E. (2007). "Clavicipitaceous fungi associated with ergoline alkaloid-containing convolvulaceae". J. Nat. Prod. 70 (12): 1955–1960. doi:10.1021/np070315t. PMID 18031017. 
  2. ↑ Komarova, E. L.; Tolkachev O. N. (2001). "The Chemistry of Peptide Ergot Alkaloids. Part 2. Analytical Methods for Determining Ergot Alkaloids". Pharm. Chem. J. 35 (10): 542–549. doi:10.1023/A:1014706301632. 
  3. ↑ 3.0 3.1 "Some Compounds With Hallucinogenic Activity". Ergot Alkaloids and Related Compounds. Handbook of Experimental Pharmacology (HEP). 49. Berlin, Heidelberg: Springer Berlin Heidelberg. 1978. pp. 567–614. doi:10.1007/978-3-642-66775-6_8. ISBN 978-3-642-66777-0. https://bibliography.maps.org/resources/download/8769. Retrieved 2025-03-30. "Elymoclavine (No.6) produces mainly sedation (ISBELL and GORODETZKY,1966). [...] In the ergolene derivatives, lysergol and elymoclavine are devoid of psychotomimetic properties. [...] Table 2. Psychotomimetic activity and some pharmacodynamic effects of structural analogues of LSD [...]" 
  4. ↑ "Indolealkylamines and Related Compounds". Hallucinogenic Agents. Bristol: Wright-Scientechnica. 1975. pp. 98–144. ISBN 978-0-85608-011-1. OCLC 2176880. https://bitnest.netfirms.com/external/Books/978-0-85608-011-1. "d-Lysergic acid amide (ergine) is the major constituent of the seeds of both Rivea corymbosa and Ipomoea violacea, together with smaller amounts of d-isolysergic acid amide (isoergine), chanoclavine, elymoclavine, and the N-(1-hydroxyethyl)amides of lysergic and isolysergic acids. [...] It is clear that the pharmacologically active constituents of ololiuqui are the isomeric lysergic acid amides. [...] Heim and his colleagues suggest that the overall effects of ololiuqui are due to these two compounds, the d-lysergic acid amide giving intoxication with strong autonomic side-effects and the d-isolysergic acid amide producing some euphoria, synaesthesia, and altered time experience. Certainly elymoclavine, lysergol, chanoclavine, and ergometrine produce no psychic changes in man (Isbell and Gorodetzky, 1966; Hofmann, 1968), though the first two do produce central excitation in animals (Yui and Takeo, 1958)." 
  5. ↑ 5.0 5.1 "Effect of alkaloids of ololiuqui in man". Psychopharmacologia 8 (5): 331–339. 1966. doi:10.1007/BF00453511. PMID 5923939. "He also found that in addition to d-lysergic acid amide, d-iso-lysergic acid amide, and chanoclavine, the seeds of both plants contained elymoclavine. [...] Elymoclavine elicits excitation and central stimulation in animals (Yui 1958), but ISBELL found that elymoclavine caused chiefly sedative effects in former addicts. [...] The results also agree with the sedative effects reported after d-lysergic aeide amide (HOFMAN 1963; ISBELL; SOLMS 1956), d-iso-lysergic acid amide (HOFMANN 1963), and elymoclavine (ISBELL). [...] ISBELL, H. : Unpublished observations.". 
  6. ↑ Schardl, C. L.; Panaccione D. G.; Tudzynski P.. The Alkaloids - Chemistry and Biology. 
  7. ↑ Dewick, P. M. (2009). Medicinal Natural Products. A Biosynthetic Approach.. 3rd Edition. Wiley. 



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