lysergic acid
{{Short description|Precursor for a range of ergoline alkaloids produced by the ergot fungus}}
{{Distinguish|Lysergic acid diethylamide}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 443929247
| ImageFile = lysergic_acid_chemical_structure.svg
| ImageSize = 180px
| ImageClass = skin-invert
| ImageFile1 = Lysergic_acid.png
| ImageSize1 = 180px
| IUPACName = 6-Methyl-9,10-didehydroergoline-8β-carboxylic acid
| SystematicName = (5R,8R)-7-Methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxylic acid
| OtherNames =
|Section1= {{Chembox Identifiers
| IUPHAR_ligand = 139
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 6461
| InChI = 1/C16H16N2O2/c1-18-8-10(16(19)20)5-12-11-3-2-4-13-15(11)9(7-17-13)6-14(12)18/h2-5,7,10,14,17H,6,8H2,1H3,(H,19,20)/t10-,14-/m1/s1
| InChIKey = ZAGRKAFMISFKIO-QMTHXVAHBD
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C16H16N2O2/c1-18-8-10(16(19)20)5-12-11-3-2-4-13-15(11)9(7-17-13)6-14(12)18/h2-5,7,10,14,17H,6,8H2,1H3,(H,19,20)/t10-,14-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = ZAGRKAFMISFKIO-QMTHXVAHSA-N
| CASNo_Ref = {{cascite|correct|??}}
| CASNo = 82-58-6
| UNII_Ref = {{fdacite|changed|FDA}}
| UNII = ITO20DAO7J
| PubChem = 6717
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 6604
| SMILES = CN1C[C@@H](C=C2[C@H]1CC3=CNC4=CC=CC2=C34)C(=O)O
}}
|Section2= {{Chembox Properties
| C= 16|H= 16|N= 2|O= 2
| Appearance =
| Density =
| MeltingPtC = 238 to 240
| MeltingPt_notes =
| BoilingPt =
| Solubility =
| pKa = pKa1 = 7.80, pKa2 = 3.30 {{cite book|last=Brown |first=H. C. |display-authors=etal |editor1-last=Braude |editor1-first=E. A. |editor2-first=F. C. |editor2-last=Nachod |title=Determination of Organic Structures by Physical Methods |publisher=Academic Press |location=New York, NY |date=1955}}}}
|Section3= {{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt =
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|Section4={{Chembox Legal status
| legal_AU =
| legal_BR = D1
| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-15 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}
| legal_US =
| legal_UK =
| legal_UN =
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}}
Lysergic acid, also known as {{sc|D}}-lysergic acid and (+)-lysergic acid, is a precursor for a wide range of ergoline alkaloids that are produced by the ergot fungus and found in the seeds of Argyreia nervosa (Hawaiian baby woodrose), and Ipomoea species (morning glories, ololiuhqui, tlitliltzin).
Amides of lysergic acid, lysergamides, are widely used as pharmaceuticals and as psychedelic drugs, e.g. lysergic acid diethylamide (LSD). Lysergic acid is listed as a Table I precursor under the United Nations Convention Against Illicit Traffic in Narcotic Drugs and Psychotropic Substances.{{cite web|url=http://www.incb.org/pdf/e/list/red.pdf |title=List of Precursors and Chemicals Frequently Used in the Illicit Manufacture of Narcotic Drugs and Psychotropic Substances Under International Control |url-status=dead |archive-url=https://web.archive.org/web/20080227224025/http://www.incb.org/pdf/e/list/red.pdf |archive-date=2008-02-27 |publisher=International Narcotics Control Board}}
The name Lysergic acid comes from the fact that it is a carboxylic acid, and it was first made by hydrolysis of various ergot alkaloids.{{cite journal|journal=Am. J. Pharm. Educ.|date=Oct 15, 2006|volume=70|issue=5|pages=98|title=Ergot and its alkaloids|last=Schiff|first=P. L.|pmid=17149427|pmc=1637017|doi=10.5688/aj700598}}
Synthesis
= Laboratory =
Lysergic acid is generally produced by hydrolysis{{cite journal|journal=J. Biotechnol.|date=Nov 17, 2001|volume=84|issue=1|pages=63–6|title=Hydrolysis of lysergamide to lysergic acid by Rhodococcus equi A4|last1=Martínková |first1=L. |last2=Kren |first2=V. |last3=Cvak |first3=L. |last4=Ovesná |first4=M. |last5=Prepechalová |first5=I.|doi=10.1016/s0168-1656(00)00332-1|pmid=11035188}} of natural lysergamides, but can also be synthesized in the laboratory by a complex total synthesis, for example by Robert Burns Woodward's team in 1956.{{cite journal|title=The Total Synthesis of Lysergic Acid|journal=J. Am. Chem. Soc.|volume=78|issue=13|pages=3087–3114|year=1956|first=Edmund C. |last1=Kornfeld|first2=E. J. |last2=Fornefeld|first3=G. Bruce |last3=Kline|first4=Marjorie J. |last4=Mann|first5=Dwight E. |last5=Morrison|first6=Reuben G. |last6=Jones|first7=R. B. |last7=Woodward|doi=10.1021/ja01594a039}} An enantioselective total synthesis based on a palladium-catalyzed domino cyclization reaction has been described in 2011 by Fujii and Ohno.{{cite journal|first1=S. |last1=Inuki |first2=A. |last2=Iwata |first3=S. |last3=Oishi |first4=N. |last4=Fujii |first5=H. |last5=Ohno |title=Enantioselective Total Synthesis of (+)-Lysergic Acid, (+)-Lysergol, and (+)-Isolysergol by Palladium-Catalyzed Domino Cyclization of Allenes Bearing Amino and Bromoindolyl Groups |journal=J. Org. Chem. |date=2011 |volume=76 |issue=7 |pages=2072–2083 |doi=10.1021/jo102388e|pmid=21361331 }} Lysergic acid monohydrate crystallizes in very thin hexagonal leaflets when recrystallized from water. Lysergic acid monohydrate, when dried (140 °C at {{convert|2|mmHg|Pa|abbr=on|disp=or}}) forms anhydrous lysergic acid.
= Biosynthesis =
The biosynthetic route is based on the alkylation of the amino acid tryptophan with dimethylallyl diphosphate (isoprene derived from 3R-mevalonic acid) giving 4-dimethylallyl-{{sc|L}}-tryptophan which is N-methylated with S-adenosyl-L-methionine. Oxidative ring closure followed by decarboxylation, reduction, cyclization, oxidation, and allylic isomerization yields {{sc|D}}-(+)-lysergic acid. The biosynthetic pathway has been reconsituted in transgenic baker's yeast.{{cite journal|title=Reconstituting the complete biosynthesis of D-lysergic acid in yeast|journal=Nature Communications|year=2022|volume=13|issue=1|page=712|doi=10.1038/s41467-022-28386-6|pmid=35132076|pmc=8821704|bibcode=2022NatCo..13..712W |last1=Wong |first1=Garrett |last2=Lim |first2=Li Rong |last3=Tan |first3=Yong Quan |last4=Go |first4=Maybelle Kho |last5=Bell |first5=David J. |last6=Freemont |first6=Paul S. |last7=Yew |first7=Wen Shan }}
Isomers
Lysergic acid is a chiral compound with two stereocenters. The isomer with inverted configuration at carbon atom 8 close to the carboxyl group is called isolysergic acid. Inversion at carbon 5 close to the nitrogen atom leads to {{sc|L}}-lysergic acid and {{sc|L}}-isolysergic acid, respectively.
File:Lysergic acid isomers.png{{clear|left}}
Legality
In the United States, Lysergic acid and Lysergic acid amide are Schedule III substances.https://www.ecfr.gov/current/title-21/chapter-II/part-1308/subject-group-ECFRf62f8e189108c4d/section-1308.13
See also
References
{{Reflist|30em}}
{{Wiktionary|lysergic|lysergic acid}}
{{Ergolines}}