Ergot

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[[File:Ergoline.png|right|thumb|The ergoline skeleton looks not entirely unlike a cock-n-balls.]]

Ergot is pronounced ur-git, '''not''' er-go. Highly toxic, it ought not be consumed. Properly modified, it has many uses, primarily due to fortuitous similarity between the ergoline skeleton and the monoamide neurotransmitters (e.g. serotonin, dopamine, ~~adrenaline~~)...

Ergot is pronounced ur-git, '''not''' er-go. Highly toxic, it ought not be consumed. Properly modified, it has many uses, primarily due to fortuitous similarity between the ergoline skeleton and the monoamide neurotransmitters (e.g. serotonin, dopamine, noradrenaline)...

Ergot alkaloids ergonovine and ergotamine (and their salts) are both original List I controlled precursors under the [https://en.wikipedia.org/wiki/Controlled_Substances_Act 1970 Controlled Substances Act]. Ergocristine was added to List I in 2010 (see the DEA's 2010-03 ''[https://www.erowid.org/library/periodicals/microgram/microgram_2010-03.pdf Microgram Journal]''). Derivatives lysergic acid and its amide ("ergine") are Schedule III controlled substances under the CSA, and ergine is a Class A precursor in the United Kingdom. Subsequent derivative lysergic acid diethylamide is an original Schedule I controlled substance, and its functional analogues (any chemical "substantially similar", as if that had any kind of precise meaning) are treated as Schedule I due to the [https://en.wikipedia.org/wiki/Federal_Analogue_Act 1986 Federal Analogue Act]. Ergotamine, lysergic acid, and ergometrine (ergonovine) are all on Table I of the INCB Red List, and thus EU Category 1 precursors. So there's clearly something worth knowing about ergot!

Ergot alkaloids ergonovine and ergotamine (and their salts) are both original List I controlled precursors under the [https://en.wikipedia.org/wiki/Controlled_Substances_Act 1970 Controlled Substances Act]. Ergocristine was added to List I in 2010 (see the DEA's 2010-03 ''[https://www.erowid.org/library/periodicals/microgram/microgram_2010-03.pdf Microgram Journal]''). Derivatives lysergic acid and its amide ("ergine") are Schedule III controlled substances under the CSA, and ergine is a Class A precursor in the United Kingdom. Subsequent derivative lysergic acid diethylamide is an original Schedule I controlled substance, and its functional analogues (any chemical "substantially similar", as if that had any kind of precise meaning) are treated as Schedule I due to the [https://en.wikipedia.org/wiki/Federal_Analogue_Act 1986 Federal Analogue Act]. Ergotamine, lysergic acid, and ergometrine (ergonovine) are all on Table I of the INCB Red List, and are thus EU Category 1 precursors. So there's clearly something worth knowing about ergot!

==Some basic terminology==

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* '''Alkaloid''': Basic (high-pH) naturally-occurring organic compounds containing nitrogen. The "true alkaloids" are biosynthesized from amino acids and contain nitrogen in a heterocycle (a cyclic structure containing more than one element).

** '''Indole''': The aromatic heterocycle C8H7N. Bicyclic pair of benzene (C6H6) and pyrrole (C4H4NH) sharing an edge. A biosynthetic precursor to the indole alkaloids, including the amino acid tryptophan and the neuroprotective antioxidant 3-indolepropionic acid (IPA).

** '''Tryptophan''': An essential amino acid (one which cannot be biosynthesized in humans), and a precursor in humans of serotonin, melatonin, and vitamin B3. Clostridium sporogenes in the human gut ~~metabolizes~~ tryptophan into indole.

** '''Tryptophan''': An essential amino acid (one which cannot be biosynthesized in humans), and a precursor in humans of serotonin, melatonin, and vitamin B3. Clostridium sporogenes in the human gut metabolize tryptophan into indole.

** '''Ergoline''': the tetracyclic structural skeleton (C14H16N2) shared by ergoline alkaloids. Also a [https://jkproducts.us/ergoline-tanning-beds/ tanning bed] by JK Products (pronounced differently).

File:Agroclavine.png|Agroclavine|alt=agroclavine

File:Elymoclavine.png|Elymoclavine|alt=Elymoclavine

File:Paspalic.png|Paspalic acid|alt=Paspalic acid

File:DLA.png|DLA|alt=D-lysergic acid

File:LSA.png|LSA|alt=D-lysergamide acid amide

File:Lsd.png|LSD|alt=D-lysergic acid diethylamide

</gallery>

==Ergoline path (biosynthesis of the ergot alkaloids)==

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===Paspalic acid===

Paspalic acid is an isomer of lysergic acid, and will spontaneously convert. Jean-Claude Gaullier's 2000 [https://patents.google.com/patent/US6242603B1/en patent] specifies a high-yield (81.6% RRi, 2.8% iso-LA) isomerization using a tetra(C1-C6)alkylammonium hydroxide. In that same patent, he cites previous isomerizations using 2N sodium hydroxide or 0.5N potassium hydroxide, reporting 59.3% RRi with NaOH (6.8% iso-LA) and 49.8% RRi with KOH (1% iso-LA), described in the Swiss journal Helvetica Chimica Acta in 1981 and 1964, respectively. [https://patents.google.com/patent/WO2005082902A1/en Cvac + Mojczek claimed] to do even better purity-wise in 2005 by following the metallic hydroxide with a methanol wash.

Paspalic acid is an isomer of lysergic acid, and will spontaneously convert. Jean-Claude Gaullier's 2000 [https://patents.google.com/patent/US6242603B1/en patent] specifies a high-yield (81.6% RRi, 2.8% iso-LA) isomerization using a tetra(C1-C6)alkylammonium hydroxide. In that same patent, he cites previous isomerizations using 2N sodium hydroxide or 0.5N potassium hydroxide, reporting 59.3% RRi with NaOH (6.8% iso-LA) and 49.8% RRi with KOH (1% iso-LA), described in the Swiss journal Helvetica Chimica Acta in 1981 and 1964, respectively. [https://patents.google.com/patent/WO2005082902A1/en Cvac + Mojczek claimed] to do even better purity-wise in 2005 by following the metallic hydroxide with a methanol wash.

===Extraction of ergopeptines from ergot broth===

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Lysergic: discovered via hydro''lys''is of ''erg''otamine (-ic: a suffix meaning "characterized by").

A Table I precursor under the [https://en.wikisource.org/wiki/United_Nations_Convention_Against_Illicit_Traffic_in_Narcotic_Drugs_and_Psychotropic_Substances UN Convention Against Psychotropic Substances] and a Schedule III controlled substance. About 15 tons of DLA (also seen as (+)-lysergic acid) are legitimately manufactured each year, primarily from submerged fermentation of special strains of Calviceps purpurea, but also from field harvests wherever eastern europeans can be convinced to tromp around filling their baskets with ~~balls of~~ mycotoxic jizz.

A Table I precursor under the [https://en.wikisource.org/wiki/United_Nations_Convention_Against_Illicit_Traffic_in_Narcotic_Drugs_and_Psychotropic_Substances UN Convention Against Psychotropic Substances] and a Schedule III controlled substance. About 15 tons of DLA (also seen as (+)-lysergic acid) are legitimately manufactured each year, primarily from submerged fermentation of special strains of Calviceps purpurea, but also from field harvests wherever eastern europeans can be convinced to tromp around filling their baskets with mycotoxic jizz.

{| class="wikitable"

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(6aR,9R)-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide is a guaranteed cure for boredom.

Hoffman first synthesized LSD ("Lysergsäurediethylamid", C20H25N3O) 1938-11-16 at Sandoz Pharmaceuticals. It was the twenty-fifth substance synthesized in a program of systematically exploring the ergot alkaloids, hence the name LSD-25. On 1943-04-19, he accidentally ingested about 250 micrograms, and discovered its potent effects. Some claim this to be ~~direct~~ evidence of God's intervention in human affairs, but I am unconvinced.

Hoffman first synthesized LSD ("Lysergsäurediethylamid", C20H25N3O) 1938-11-16 at Sandoz Pharmaceuticals. It was the twenty-fifth substance synthesized in a program of systematically exploring the ergot alkaloids, hence the name LSD-25. On 1943-04-19, he accidentally ingested about 250 micrograms, and discovered its potent effects. Some claim this to be evidence of God's direct intervention in human affairs, but I am unconvinced.

===Production from DLA===

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===Testing===

UV flourescence spectroscopy will destroy the sample.

* Ehrlich '~~''WRITEME'''~~

The Ehrlich reagent is sensitive to indole alkaloids, turning purple or dark pink. This is qualitative (basically "present" or "not present"), has many false positives (pyridoxine, other tryptamines...), and can't speak to purity. If it fails, however, you almost certainly have no ergoline, and will not be going to space today. The Marquis reagent ought turn "olive black", whatever that is. The Marquis reagent is [https://www.erowid.org/columns/crew/2015/06/marquis-and-lsd-is-color-change-visible/ not considered a good test for LSD].

* NMR '''WRITEME'''

====Mass spectrometry====

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* [https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Complex_Molecular_Synthesis_(Salomon)/06%3A_Amino_Acids_and_Alkaloids/6.04%3A_Lysergic_Acid Biosynthesis of Tryptophan and Lysergic Acid]. Salomon. ''Complex Molecular Synthesis'' LibreTexts Chemistry 2021.

* [https://www.sciencedirect.com/science/article/abs/pii/S1099483120300298 Biosynthesis, total synthesis, and biological profiles of ergot alkaloids]. Tasker & Wipf. ''The Alkaloids: Chemistry and Biology'' 2020.

* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829483/ Return of the Lysergamides] Parts I-VII. Brandt et al. ''Drug Testing and Analysis'' 2016-09.

* [https://sci-hub.se/10.1023/A:1014050926916 The Chemistry of Peptide Ergot Alkaloids]. Komarova & Tolkachev. ''Pharmaceutical Chemistry Journal'' 2001-02, translated 2001-09.

* Lysergamides Revisited. Nichols et al. ''Hallucinogens: An Update''. National Institute on Drug Abuse Research Monograph Series #146 1994.

Ergot: Difference between revisions

Dank (talk | contribs)

@@ Line 1: / Line 1: @@
 [[File:Ergoline.png|right|thumb|The ergoline skeleton looks not entirely unlike a cock-n-balls.]]
-Ergot is pronounced ur-git, '''not''' er-go. Highly toxic, it ought not be consumed. Properly modified, it has many uses, primarily due to fortuitous similarity between the ergoline skeleton and the monoamide neurotransmitters (e.g. serotonin, dopamine, adrenaline)...
+Ergot is pronounced ur-git, '''not''' er-go. Highly toxic, it ought not be consumed. Properly modified, it has many uses, primarily due to fortuitous similarity between the ergoline skeleton and the monoamide neurotransmitters (e.g. serotonin, dopamine, noradrenaline)...
-Ergot alkaloids ergonovine and ergotamine (and their salts) are both original List I controlled precursors under the [https://en.wikipedia.org/wiki/Controlled_Substances_Act 1970 Controlled Substances Act]. Ergocristine was added to List I in 2010 (see the DEA's 2010-03 ''[https://www.erowid.org/library/periodicals/microgram/microgram_2010-03.pdf Microgram Journal]''). Derivatives lysergic acid and its amide ("ergine") are Schedule III controlled substances under the CSA, and ergine is a Class A precursor in the United Kingdom. Subsequent derivative lysergic acid diethylamide is an original Schedule I controlled substance, and its functional analogues (any chemical "substantially similar", as if that had any kind of precise meaning) are treated as Schedule I due to the [https://en.wikipedia.org/wiki/Federal_Analogue_Act 1986 Federal Analogue Act]. Ergotamine, lysergic acid, and ergometrine (ergonovine) are all on Table I of the INCB Red List, and thus EU Category 1 precursors. So there's clearly something worth knowing about ergot!
+Ergot alkaloids ergonovine and ergotamine (and their salts) are both original List I controlled precursors under the [https://en.wikipedia.org/wiki/Controlled_Substances_Act 1970 Controlled Substances Act]. Ergocristine was added to List I in 2010 (see the DEA's 2010-03 ''[https://www.erowid.org/library/periodicals/microgram/microgram_2010-03.pdf Microgram Journal]''). Derivatives lysergic acid and its amide ("ergine") are Schedule III controlled substances under the CSA, and ergine is a Class A precursor in the United Kingdom. Subsequent derivative lysergic acid diethylamide is an original Schedule I controlled substance, and its functional analogues (any chemical "substantially similar", as if that had any kind of precise meaning) are treated as Schedule I due to the [https://en.wikipedia.org/wiki/Federal_Analogue_Act 1986 Federal Analogue Act]. Ergotamine, lysergic acid, and ergometrine (ergonovine) are all on Table I of the INCB Red List, and are thus EU Category 1 precursors. So there's clearly something worth knowing about ergot!
 ==Some basic terminology==
@@ Line 12: / Line 12: @@
 * '''Alkaloid''': Basic (high-pH) naturally-occurring organic compounds containing nitrogen. The "true alkaloids" are biosynthesized from amino acids and contain nitrogen in a heterocycle (a cyclic structure containing more than one element).
 ** '''Indole''': The aromatic heterocycle C<sub>8</sub>H<sub>7</sub>N. Bicyclic pair of benzene (C<sub>6</sub>H<sub>6</sub>) and pyrrole (C<sub>4</sub>H<sub>4</sub>NH) sharing an edge. A biosynthetic precursor to the indole alkaloids, including the amino acid tryptophan and the neuroprotective antioxidant 3-indolepropionic acid (IPA).
-** '''Tryptophan''': An essential amino acid (one which cannot be biosynthesized in humans), and a precursor in humans of serotonin, melatonin, and vitamin B3. Clostridium sporogenes in the human gut metabolizes tryptophan into indole.
+** '''Tryptophan''': An essential amino acid (one which cannot be biosynthesized in humans), and a precursor in humans of serotonin, melatonin, and vitamin B3. Clostridium sporogenes in the human gut metabolize tryptophan into indole.
 ** '''Ergoline''': the tetracyclic structural skeleton (C<sub>14</sub>H<sub>16</sub>N<sub>2</sub>) shared by ergoline alkaloids. Also a [https://jkproducts.us/ergoline-tanning-beds/ tanning bed] by JK Products (pronounced differently).
+<gallery>
+File:Agroclavine.png|Agroclavine|alt=agroclavine
+File:Elymoclavine.png|Elymoclavine|alt=Elymoclavine
+File:Paspalic.png|Paspalic acid|alt=Paspalic acid
+File:DLA.png|DLA|alt=D-lysergic acid
+File:LSA.png|LSA|alt=D-lysergamide acid amide
+File:Lsd.png|LSD|alt=D-lysergic acid diethylamide
+</gallery>
 ==Ergoline path (biosynthesis of the ergot alkaloids)==
@@ Line 44: / Line 53: @@
 ===Paspalic acid===
-Paspalic acid is an isomer of lysergic acid, and will spontaneously convert. Jean-Claude Gaullier's 2000 [https://patents.google.com/patent/US6242603B1/en patent] specifies a high-yield (81.6% RRi, 2.8% iso-LA) isomerization using a tetra(C1-C6)alkylammonium hydroxide. In that same patent, he cites previous isomerizations using 2N sodium hydroxide or 0.5N potassium hydroxide, reporting 59.3% RRi with NaOH (6.8% iso-LA) and 49.8% RRi with KOH (1% iso-LA), described in the Swiss journal Helvetica Chimica Acta in 1981 and 1964, respectively. [https://patents.google.com/patent/WO2005082902A1/en Cvac + Mojczek claimed] to do even better purity-wise in 2005 by following the metallic hydroxide with a methanol wash.
+Paspalic acid is an isomer of lysergic acid, and will spontaneously convert. Jean-Claude Gaullier's 2000 [https://patents.google.com/patent/US6242603B1/en patent] specifies a high-yield (81.6% RRi, 2.8% iso-LA) isomerization using a tetra(C1-C6)alkylammonium hydroxide. In that same patent, he cites previous isomerizations using 2N sodium hydroxide or 0.5N potassium hydroxide, reporting 59.3% RRi with NaOH (6.8% iso-LA) and 49.8% RRi with KOH (1% iso-LA), described in the Swiss journal <i>Helvetica Chimica Acta</i> in 1981 and 1964, respectively. [https://patents.google.com/patent/WO2005082902A1/en Cvac + Mojczek claimed] to do even better purity-wise in 2005 by following the metallic hydroxide with a methanol wash.
 ===Extraction of ergopeptines from ergot broth===
@@ Line 57: / Line 66: @@
 Lysergic: discovered via hydro''lys''is of ''erg''otamine (-ic: a suffix meaning "characterized by").
-A Table I precursor under the [https://en.wikisource.org/wiki/United_Nations_Convention_Against_Illicit_Traffic_in_Narcotic_Drugs_and_Psychotropic_Substances UN Convention Against Psychotropic Substances] and a Schedule III controlled substance. About 15 tons of DLA (also seen as (+)-lysergic acid) are legitimately manufactured each year, primarily from submerged fermentation of special strains of Calviceps purpurea, but also from field harvests wherever eastern europeans can be convinced to tromp around filling their baskets with balls of mycotoxic jizz.
+A Table I precursor under the [https://en.wikisource.org/wiki/United_Nations_Convention_Against_Illicit_Traffic_in_Narcotic_Drugs_and_Psychotropic_Substances UN Convention Against Psychotropic Substances] and a Schedule III controlled substance. About 15 tons of DLA (also seen as (+)-lysergic acid) are legitimately manufactured each year, primarily from submerged fermentation of special strains of Calviceps purpurea, but also from field harvests wherever eastern europeans can be convinced to tromp around filling their baskets with mycotoxic jizz.
 {| class="wikitable"
@@ Line 90: / Line 99: @@
 (6aR,9R)-N,N-diethyl-7-methyl-4,6,6a,7,8,9-hexahydroindolo[4,3-fg]quinoline-9-carboxamide is a guaranteed cure for boredom.
-Hoffman first synthesized LSD ("Lysergsäurediethylamid", C<sub>20</sub>H<sub>25</sub>N<sub>3</sub>O) 1938-11-16 at Sandoz Pharmaceuticals. It was the twenty-fifth substance synthesized in a program of systematically exploring the ergot alkaloids, hence the name LSD-25. On 1943-04-19, he accidentally ingested about 250 micrograms, and discovered its potent effects. Some claim this to be direct evidence of God's intervention in human affairs, but I am unconvinced.
+Hoffman first synthesized LSD ("Lysergsäurediethylamid", C<sub>20</sub>H<sub>25</sub>N<sub>3</sub>O) 1938-11-16 at Sandoz Pharmaceuticals. It was the twenty-fifth substance synthesized in a program of systematically exploring the ergot alkaloids, hence the name LSD-25. On 1943-04-19, he accidentally ingested about 250 micrograms, and discovered its potent effects. Some claim this to be evidence of God's direct intervention in human affairs, but I am unconvinced.
 ===Production from DLA===
@@ Line 110: / Line 119: @@
 ===Testing===
 UV flourescence spectroscopy will destroy the sample.
-* Ehrlich '''WRITEME'''
+The Ehrlich reagent is sensitive to indole alkaloids, turning purple or dark pink. This is qualitative (basically "present" or "not present"), has many false positives (pyridoxine, other tryptamines...), and can't speak to purity. If it fails, however, you almost certainly have no ergoline, and will not be going to space today. The Marquis reagent ought turn "olive black", whatever that is. The Marquis reagent is [https://www.erowid.org/columns/crew/2015/06/marquis-and-lsd-is-color-change-visible/ not considered a good test for LSD].
 * NMR '''WRITEME'''
 ====Mass spectrometry====
@@ Line 155: / Line 166: @@
 * [https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Book%3A_Complex_Molecular_Synthesis_(Salomon)/06%3A_Amino_Acids_and_Alkaloids/6.04%3A_Lysergic_Acid Biosynthesis of Tryptophan and Lysergic Acid]. Salomon. ''Complex Molecular Synthesis'' LibreTexts Chemistry 2021.
 * [https://www.sciencedirect.com/science/article/abs/pii/S1099483120300298 Biosynthesis, total synthesis, and biological profiles of ergot alkaloids]. Tasker & Wipf. ''The Alkaloids: Chemistry and Biology'' 2020.
+* [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4829483/ Return of the Lysergamides] Parts I-VII. Brandt et al. ''Drug Testing and Analysis'' 2016-09.
 * [https://sci-hub.se/10.1023/A:1014050926916 The Chemistry of Peptide Ergot Alkaloids]. Komarova & Tolkachev. ''Pharmaceutical Chemistry Journal'' 2001-02, translated 2001-09.
 * Lysergamides Revisited. Nichols et al. ''Hallucinogens: An Update''. National Institute on Drug Abuse Research Monograph Series #146 1994.