Lysergol

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Structural formula
Structural formula of lysergol
General
Surname Lysergol
other names
  • 9,10-didehydro-8 β -hydroxymethyl-6-methylergoline
  • (6a R , 9 R ) -9-Hydroxymethyl-7-methyl-4,6,6a, 7,8,9-hexahydro-indolo [4,3- fg ] quinoline
Molecular formula C 16 H 18 N 2 O
External identifiers / databases
CAS number 602-85-7
EC number 210-024-5
ECHA InfoCard 100.009.113
PubChem 14987
ChemSpider 14267
Wikidata Q6710130
properties
Molar mass 254.3 g mol −1
Physical state

firmly

Melting point

approx. 245 ° C (with decomposition)

safety instructions
GHS labeling of hazardous substances
06 - Toxic or very toxic

danger

H and P phrases H: 300-315-319-335
P: 261-264-301 + 310-305 + 351 + 338
Toxicological data

0.32 mg kg −1 ( LD 50 ,  rabbit ,  iv )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Lysergol is a naturally occurring chemical compound . It is an alkaloid belonging to the group of clavins , which is produced by numerous representatives of ergot relatives and other sac fungi that parasitize on sweet grasses . Lysergol can also be found in numerous bindweed plants .

history

Lysergol and its C-8 epimer isolysergol were first partially synthesized and described by Arthur Stoll , Albert Hofmann and Werner Schlientz in 1949. The natural occurrence of lysergol could be proven in 1960 by Yamatodani with the help of paper chromatography .

Occurrence

Lysergol was first detected on Elymus semicostatus , a species of couch grass . The ergot infestation is responsible for the production of this alkaloid . Lysergol can also be obtained from a saprophytic culture of ergot fungi. Particularly noticeable is the occurrence of lysergol alongside other clavins in bindweed plants .

To a small extent it is part of the toxic principle and the psychotropic effect of the ritually used bindweed herbs ololiuqui (especially from Turbina corymbosa ) and tlitliltzin ( Ipomoea violacea and other types of Ipomoea ) in addition to the primary active substances LSA and LSH . An infestation with ergot fungi of the genus Periglandula is held responsible for the occurrence of clavins, such as lysergol, in bindweed plants .

presentation

Partially synthetic representation

Lysergol can be produced partially synthetically from lysergic acid . Lysergol is the reaction product of the reduction of lysergic acid methyl ester with lithium aluminum hydride (LiAlH 4 ).

Total synthesis

Lysergol can be produced enantioselectively in a multistage process starting from ethinylaziridine and 4-bromoindol-3-yl-acetaldehyde with palladium- mediated domino cyclization. In the first reaction step, with a tosyl -protected Ethinylaziridin with formaldehyde under palladium and indium - catalysis reductively to give the corresponding chiral reacted 1,3-amino alcohol. The center of chirality of the amino alcohol corresponds to the later stereocenter in position C-8 of the lysergol. In the sense of a Nozaki-Hiyama-Kishi reaction with 4-bromoindol-3-yl-acetaldehyde, the tosylated 1- (4-bromoindol-3-yl) -4- (2-phenyl) is formed as an intermediate product with nickel and chromium catalysis -1,3-oxazinan-5-yl) butyn-2-ol obtained. From the information obtained from this connection Allen goes into the subsequent Dominozyklisierung with palladium catalysis the Ergolin -Grundgerüst forth. After removing the protective groups, the lysergol can be isolated.

properties

Chemical and physical properties

Lysergol is a colorless whitish to slightly yellowish substance. It is soluble in methanol and ethanol , but only very sparingly soluble in chloroform and water. It crystallizes from ethanol in the form of prisms.

Lysergol gives the typical detection reactions to ergot alkaloids. These include in particular the Van Urk reaction and detection with the Allport Cocking reagent . The UV spectrum of the substance shows maxima at 225, 242 and 312 nm.

Stereochemistry

Lysergol is a chiral natural product with two centers of asymmetry . It has an all ( R ) configuration. Its C-8 epimer, isolysergol, could also be detected as a natural product. In contrast, the C-5 epimer is of no importance.

Biological importance

Lysergol is one of the most pharmacologically active compounds from the clavine group. Lysergol has a high affinity for 5-HT 1 receptors , and in particular to 5-HT 1B - , 5-HT 1D - and 5-HT 1F receptors. Lysergol acts as a potent partial agonist at 5-HT 1B receptors . With lower potency, lysergol also activates 5-HT 2A receptors. In contrast, lysergol is an antagonist at α 1 -adrenoceptors with moderate receptor affinity. Lysergol acts as a partial agonist at α 2 -adrenoceptors . Lysergol is seen as a crucial component of the grazing cattle disease Fescue toxicosis , which is caused by grazing on grasses that have been infected with ergot fungi. Due to the strong side effect profile (such as an increase in blood pressure ), lysergol is of no relevance as a psychotropic substance.

Individual evidence

  1. ↑ a b c d data sheet Lysergol, 97% from Sigma-Aldrich , accessed on October 31, 2013 ( PDF ).
  2. ↑ a b c d Abe M, Yamatodani S, Yamano T, Kosumoto M: Isolation of lysergol, lysergene and lysergine from the saprophytic cultures of ergot fungi . In: Agr. Biol. Chem . 25, 1961, pp. 594-595.
  3. ↑ a b c Stoll A, Hofmann A, Schlientz W: The stereoisomeric lysergole and dihydro-lysergole. 15. Communication on ergot alkaloids . In: Helv. Chim. Acta . 32, No. 6, 1949, pp. 1947-1956. doi : 10.1002 / hlca.19490320622 .
  4. ↑ Yamatodani S: Researches on ergot fungus. Part XL. On the paper chromatography of water-soluble ergot alkaloids . In: Ann. Rep. Takeda Res. Lab . 19, 1960, pp. 1-7.
  5. ↑ Eckart Eich: Tryptophan-derived alkaloid . In: Solanaceae and convolvulaceae - secondary metabolites: biosynthesis, chemotaxonomy, biological and economic significance . Springer, 2008, ISBN 3540745408 , pp. 213-260.
  6. ↑ Steiner U, Leibner S, Schardl CL, Leuchtmann A, Leistner E: Periglandula, a new fungal genus within the Clavicipitaceae and its association with Convolvulaceae . In: Mycologia . 103, No. 5, 2011, pp. 1133-1145. doi : 10.3852 / 11-031 . PMID 21558502 .
  7. ↑ Inuki S, Iwata A, Oishi S, Fujii N, Ohno H: Enantioselective total synthesis of (+) - lysergic acid, (+) - lysergol, and (+) - isolysergol by palladium-catalyzed domino cyclization of allenes bearing amino and bromoindolyl groups . In: J Org Chem . 76, No. 7, 2011, pp. 2072-2083. doi : 10.1021 / jo102388e . PMID 21361331 .
  8. ↑ Agurell S: Isolysergol from saprophytic cultures of ergot . In: Acta Pharm. Suecica . 3, 1966, pp. 7-10.
  9. ↑ Heinz Pertz, Eckart Eich: Ergot alkaloids and their derivatives as ligands for serotoninergic, dopaminergic, and adrenergic receptors . In: Vladimir Kren, Ladislav Cvak (eds.): Ergot: The Genus Claviceps. Medicinal and Aromatic Plants - Industrial Profiles . CRC Press, 2004, ISBN 0203304195 , pp. 411-440.
  10. ↑ Pertz H: 5-Hydroxytryptamine (5-HT) contracts the guinea-pig isolated iliac artery via 5-HT1-like and 5-HT2 receptors . In: Naunyn Schmiedebergs Arch Pharmacol . 348, No. 6, 1993, pp. 558-565. PMID 8133899 .
  11. ↑ Pertz H: Naturally occurring clavines: antagonism / partial agonism at 5-HT2A receptors and antagonism at alpha 1-adrenoceptors in blood vessels . In: Planta Med . 62, No. 5, 1996, pp. 387-392. PMID 8923801 .
  12. ↑ Fallarero A, Pohjanoksa K, Wissel G, Parkkisenniemi-Kinnunen UM, Xhaard H, Scheinin M, Vuorela P: High-throughput screening with a miniaturized radioligand competition assay identifies new modulators of human α2-adrenoceptors . In: Eur J Pharm Sci . 47, No. 5, 2012, pp. 941-951. doi : 10.1016 / j.ejps.2012.08.021 . PMID 2298240 .
  13. ^ Hill NS, Thompson FN, Stuedemann JA, Rottinghaus GW, Ju HJ, Dawe DL, Hiatt EE 3rd: Ergot alkaloid transport across ruminant gastric tissues . In: J Anim Sci . 79, No. 2, 2001, pp. 542-549. PMID 11219466 .
  14. ↑ H. Panda: Handbook on Drugs from Natural Sources . ASIA PACIFIC BUSINESS PRESS Inc., 2010, ISBN 978-8-178-33133-1 ( limited preview in Google Book Search).