Sintesi dell'LSD dall'acido lisergico tramite PyBOP
- Thread starter William D.
- Start date
Ciao ragazzi, qualcuno conosce l'idrolisi dell'ergotamina con sodio ditionito e KOH?
Questo argomento sembra molto sottovalutato. Sembra davvero rivoluzionario rispetto al modo in cui ho imparato a produrlo.
Ho letto uno scambio in cui qualcuno suggeriva che l'estere metilico potrebbe racemizzare durante l'idrolisi. È un problema che riguarda l'isomero d entiopuro? Ho notato che la TLC non è inclusa nel lavoro.
Il rotovap è davvero facoltativo? Questo metodo si avvicina alla sintesi in vasca da bagno senza di essa. Niente calore? Sembra più semplice dell'Mdma o dell'anfetamina.
Cosa mi sfugge? Si lavora sotto luce gialla o rossa? Quali sono le maggiori complicazioni? Il prodotto finale produce isolato?
Ho letto uno scambio in cui qualcuno suggeriva che l'estere metilico potrebbe racemizzare durante l'idrolisi. È un problema che riguarda l'isomero d entiopuro? Ho notato che la TLC non è inclusa nel lavoro.
Il rotovap è davvero facoltativo? Questo metodo si avvicina alla sintesi in vasca da bagno senza di essa. Niente calore? Sembra più semplice dell'Mdma o dell'anfetamina.
Cosa mi sfugge? Si lavora sotto luce gialla o rossa? Quali sono le maggiori complicazioni? Il prodotto finale produce isolato?
- By Nicoino
Ottenere un LA ragionevolmente puro è una rottura, quasi tutte le idrolisi portano a un prodotto marrone/nero che deve essere purificato.
Anche con LA di buona qualità la miscela di reazione di accoppiamento diventa marrone-nera e il lavoro non è così semplice come viene detto (forse se si inizia con precursori puri al 100%, solventi degassati e attrezzature professionali si ha una piccola possibilità che non accada, ma per il chimico casalingo la soluzione scura deve essere prevista).
La purificazione del prodotto non è uno scherzo se non si ha accesso alla cromatografia su colonna o se non si vogliono rimuovere litri di solvente sotto vuoto.
Anche con LA di buona qualità la miscela di reazione di accoppiamento diventa marrone-nera e il lavoro non è così semplice come viene detto (forse se si inizia con precursori puri al 100%, solventi degassati e attrezzature professionali si ha una piccola possibilità che non accada, ma per il chimico casalingo la soluzione scura deve essere prevista).
La purificazione del prodotto non è uno scherzo se non si ha accesso alla cromatografia su colonna o se non si vogliono rimuovere litri di solvente sotto vuoto.
- By PlanckB1
Questa è stata anche la mia esperienza: ripetute ricristallizzazioni dell'acido lisergico dall'idrolisi hanno dato come risultato una polvere che diventa ogni volta di colore marrone più chiaro, ma non è ancora così chiara/pura come ci si aspetterebbe. Consigliate la cromatografia su colonna del LA o solo la cromatografia su colonna dell'LSD finale a base libera?
- By Nicoino
Non credo che valga per il LA, probabilmente con un buon lavoro e un numero sufficiente di esperimenti non è nemmeno necessario per il prodotto finale.
Grandi chimici dell'acido come pichard sintetizzavano chili ogni mese, e dubito davvero che fossero in grado di cromatografare quella quantità di prodotto, quasi impossibile con una fabbrica.
Grandi chimici dell'acido come pichard sintetizzavano chili ogni mese, e dubito davvero che fossero in grado di cromatografare quella quantità di prodotto, quasi impossibile con una fabbrica.
@G.Patton @William Dampier, si può usare invece l'idrossido di sodio o l'idrossido di potassio?
L'idrossido di ammonio viene utilizzato per raggiungere un determinato PH o dona uno ione?
Qualche fornitore offre: "idrossido di ammonio (NH4OH)"?
L'idrossido di ammonio viene utilizzato per raggiungere un determinato PH o dona uno ione?
Qualche fornitore offre: "idrossido di ammonio (NH4OH)"?
Ciao @William Dampier grazie per il percorso di sintesi.
Non sono un esperto, ho solo esperienza di isomerizzazione del CBD a d8.
Ora sto cercando di capire se è possibile produrre LSD.
I miei obiettivi attuali sono:
Non sono un esperto, ho solo esperienza di isomerizzazione del CBD a d8.
Ora sto cercando di capire se è possibile produrre LSD.
I miei obiettivi attuali sono:
- Trovare un percorso dettagliato dall'estere metilico dell'acido D-Lisergico.
- Ottenere tutti i reagenti
- Imparare a maneggiare i reagenti in modo sicuro
- Imparare la cromatografia su strato sottile
- Apprendimento della cromatografia su colonna (Flash)
- Preparare l'LSD
- Riciclaggio e smaltimento sicuro dei reagenti
- Scrivete che ci servono 0,84 g di dietilammina (cas 109-89-7), è corretto?
- Lo chiedo perché secondo https://www.sigmaaldrich.com/ è un liquido e l'ho visto da venditori cinesi venduto in kg.
- Quali sono le piastre TLC più adatte per questa sintesi?
- Iltipo H non contiene legante gesso calcinato o agente fluorescente.
- Iltipo G non contiene agente fluorescente, ma contiene legante di gesso calcinato.
- Il tipoHF254 contiene agente fluorescente, non contiene legante di gesso calcinato.
- Il tipoGF254 contiene sia il legante gesso calcinato che l'agente fluorescente.
- Potete aiutarmi con il percorso dell'estere metilico dell'acido D-Lisergico?
- By HerrHaber
Si dà il caso che la dietilammina non sia regolamentata in alcuni Paesi e che io abbia accesso ad essa, per cui si può pensare di inviarne quantità inferiori alla media, soprattutto in forma protetta. In questa particolare sintesi penso che possa essere eluita attraverso il GF254.
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- By HerrHaber
In questa situazione particolare il liquido viene pesato per la precisione... volumetricamente è necessaria una micropipetta per ottenere quantità precise. A volte la precisione è decisiva nella sintesi, anche la metil-dietilammina NMe(Et)2 deve essere precisa. Raramente si pesano grandi volumi su .... poiché il volume è più facile a seconda della viscosità e della reattività. I liquidi reattivi possono essere trattati con una siringa in base al volume, ma a volte, se la quantità è piccola, viene pipettata in un matraccio su una bilancia, goccia a goccia, fino a raggiungere la massa necessaria. L'atmosfera inerte è complicata e richiede una linea Schlenk e un'attrezzatura, idealmente una glovebox (linea Schlenk e tutti i parafrenalia come le trappole per l'argon e l'azoto liquido), glovebox che ho fantasticato di costruire (in realtà ho costruito un microscopio funzionante quando avevo sette anni).
Esiste un'alternativa all'uso di una macchina rotovap?
- By William D.
Set per distillazione sotto vuoto
Set di 5 pezzi con 24/29 giunti per una distillazione sottovuoto precisa, in vetro borosilicato resistente.Eliminando le congetture sulle dimensioni corrette di ciascun componente, i set di distillazione sono completi e pronti all'uso. Con pezzi resistenti alle sostanze chimiche e alle temperature, la vetreria...
us.vwr.comLa mia domanda è se un'altra ammina può sostituire la dietilmetilammina. Ad esempio la diisopropilammina o la diisopropiletilammina? Qualunque cosa?
- By SYN
Yes should be possible.
Amide Synthesis
The direct coupling between a carboxylic acid and an amine is competing with the acid/base proton exchange and it hardly is a suitable choice in synthetic chemistry.
www.fishersci.nl
- By mycelium
There are several animes that can be used in place of diethylamine, but they are not as strong or awesome. Let me see if I can find it and cut n paste, hold on
edical literature. A number of analogues of LSD have maintained the diethylamide group unchanged, but additions or changes have been made in the pyrrole ring.
ALD-52. 1-Acetyl-N,N-diethyllysergamide. This material has been explored in the 50-175 microgram range and there are a number of human trials reported, with varying conclusions. One found that there was less visual distortion than with LSD and it seems to produce less anxiety and was somewhat less potent than LSD. Another report claimed it was more effective in increasing blood pressure. Yet another could not tell them apart. ALD-52 just may have been the drug that was sold as "Orange Sunshine" during the "Summer of Love" in the late '60's. Or "Orange Sunshine" may have been, really, LSD. This was the focus of a fascinating trial where two defendants were accused of distributing LSD, whereas they claimed that it was ALD-52 which was not an illegal drug. The prosecution claimed that as it hydrolyses readily to LSD, for all intents and purposes it was LSD, and anyway, you had to go through the illegal LSD to get to ALD-52 by any of the known chemical syntheses. The defendants were found guilty. And yet, I do not know who has actually measured the speed or ease of that reaction. If ALD-52 hydrolyses so easily to LSD, and the body is indeed a hydrolytic instrument, then these two drugs should be absolutely equivalent in every particular, This is the ergot equivalent of the psilocybin to psilocin argument, except this is an acetamide rather than a phosphate ester. MLD-41. 1-Methyl-N,N-diethyllysergamide. The 1-methyl homologue of LSD is has more of somatic than sensory effect, has fewer visuals and is less well accepted than LSD, with the range of dosages being from 100 to 300 micrograms. This indicates that it is perhaps a third the potency of LSD which is in accord with both pupilary dilation and reflex action. However, the cardiovascular responses are actually increased. Besides being less potent than LSD, it appears to have a slower onset but it is equally long lived. There is cross-tolerance between MLD-41 and LSD. BOL-148. 2-Bromo-N,N-diethyllysergamide. This synthetic ergot derivative, along with its 1-methyl homologue MBL-61 (mentioned below) should be used as powerful tools for studying the mechanism of action of LSD in the human animal. It does not have LSD-like effects in man. At 6 to 10 milligrams orally, there are some mental changes noted. But in another study, 20 milligrams was administered a day to a subject for 7 days, and there were no reported effects. And yet it is as potent a serotonin agonist as is LSD. How can serotonin be argued as a neurotransmitter that is a major player in explaining the action of psychedelic drugs, when this compound is nearly without activity. There are some suggestions that an intravenous route may be more effective. I have heard of effects being noted at maybe a milligram and a short (2-3 hour) intoxication following 20 milligrams administered over a 20 minute period. I was involved many years ago in a study of radio-labelled BOL-148 which was made by the bromination of LSD. I was quite sure that the only radioactive material present was BOL-148, but there could well have been some unreacted LSD still present which would, of course, still be psychoactive. The synthesis is not clean -- I was tempted to make an entry for this compound if only to reproduce Albert Hofmann's original published experimental procedure. He reacted 13.2 grams of N-bromosuccinimide (in 400 mL dioxane, with 1.2 liters of dioxane containing 25 grams of LSD. This gave 11 grams of crude product which had to be recrystallized. The radioactive syntheses uses effectively elemental bromine, and gave yields of from 5 to 15%. Visualize that reaction! A warm flask containing over a quart of warm solvent in which there was maybe half a million doses of LSD. 1-Hydroxymethyl-LSD, 1-dimethylaminomethyl-LSD and 2-iodo-LSD. These three additional compounds are shown here because they were described in a synthetic flurry that followed the discovery the activity of LSD. But at the moment I know neither their internal Sandoz codes nor if they had ever been explored in man. This is a kind of frustrating catch-all entry, in that the long index will send you here, and once here you realize that nothing is known. Well, at least the compounds are known, and perhaps there is something in the Sandoz vaults that might be interesting. I do not have access to them. MBL-61. 2-Bromo-N,N-diethyl-1-methyllysergamide. This is the compound BOL-148 (mentioned above) with a methyl group attached to the 1-position of the indole ring (LSD has a hydrogen there). This would be an even more tantalizing challenge to the serotonin theory for central activity of the psychedelics, in that it is without any activity in man at an oral dose of 14 milligrams (similar to the inactivity of the BOL-61 compound, but it is some five times more potent as a serotonin agonist. With it, as with the iodinated analogue MIL, there are many examples of the compromising of scientific integrity in the quest for funds and recognition. Both compounds are as effective as LSD itself in displacing labelled LSD that is bound to the post-synaptic serotonin receptor sites in animal brains. But neither of them show any LSD-like activity. But both have been labelled with 11C or 122I to give positron emitting forms that can be administered to man and localized in a positron emission tomography instrument (a PET scanner). I was at a meeting of a NIDA study section a few years ago, where some one presented some findings with a group of subjects who were complaining of continuing mental problems allegedly due to LSD exposure. A chart was put up showing the outline of the brain showing the locations of the EEG foci that were observed in one of these subjects. Along side it was a PET scan showing the distribution of radioactive LSD in a subject. The purpose was to discuss the similarities and differences of the coordinates of electrical activity and radio-isotope concentration. I innocently asked what positron isotope had been used, as I did not know of any successful positron labelling of LSD. Carbon 11, I was told. Where in the molecule was the label incorporated, I asked. In the 1-position methyl group. It was finally acknowledged that the compound that had actually been used was 2-iodo-1-methyl-LSD, our MIL compound, which is quite a different world. A pharmacologist might say that they are similar in action (looking at serotonin, not psychedelic action), and a chemist might say they are of similar structure (looking at the upper 80% of the molecule. But they are different compounds. This is a most subtle form of deceit. It is, in fact, out and out dishonest, but it looks good up there on the screen at a lecture. Let me mention in passing, that there are three stereoisomers possible for d-LSD. There are d-iso-LSD, l-LSD, and l-iso-LSD. The inversion of the stereochemistry of the attached diethylcarboxyamido group of d-LSD gives the diastereoisomer (d-iso-LSD) which is a frequent synthetic impurity of d-LSD itself. The corresponding optical antipodes l-LSD and l-iso-LSD are also known and have been tasted. All three are completely inactive: d-iso-LSD shows no psychological changes at an oral dose of 4 milligrams; l-LSD none at up to 10 milligrams orally; and l-iso-LSD none at 500 micrograms orally. These dramatic decreases in potency show both the stereoselectivity of the native LSD molecule in producing its central effects, and the LSD-free purity of these isomers. The second major location of variations in the structure of LSD has been in the nature of the alkyl groups on the amide nitrogen atom. Some of these are Sandoz syntheses, some are from other research groups, and a few of them are found in nature. Some of these have been studied in man, and some have not. A few of the original clutch of Sandoz compounds have both 1-substituents and amide alkyl (R) group variations: indole--- amide nitrogen substituents --- R=R=R=code name -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -CH3 -CH3 -COCH3 -CH3 -H -CH3 -CH2CH3 -(CH2)2CH3 -CH(CH3)CH2OH -CH(CH3)CH2OH -(CH2)CH3 -CH(CH3)CH2CH2OH -(CH2)4CH3 -CH(CH3)CH2CH2CH3 -CH(CH2CH3)2 -(CH2)5CH3 -CH(CH3)CH2CH2CH2CH3 -(CH2)6CH3 -CH(CH3)CH2CH2CH2CH2CH3 -CH3 -CH2CH3 -(CH2)2CH3 -CH(CH3)2 -CH(CH3)CH2C6H5 -CH2CH3 -(CH2)2CH3 -(CH2)2CH3 -CH(CH3)2 -CH2CH=CH2 -(CH2)2CH3 -CH2CH2CH2CH2- -CH2CH=CHCH2- -CH2CH2CH2CH2CH2- -CH2CH2OCH2CH2- -CH2CH3 -CH(CH2CH3)CH2OH -COCH3 -CH2CH2CH2CH2- -H -H -H -H -H* -H -H* -H* -H -H* -H -H -H* -H -H* -CH3 -CH3 -CH3 -CH3 -CH3* -CH2CH3 -CH2CH3 -(CH2)2CH3 -CH(CH3)2 -CH2CH=CH2 -(CH2)3CH3 -H -H* -CH2CH3 LA-111 LAE-32 Ergonovine Methergine DAM-57 LAMP LSD-25 DAL LPD-824 LSM-775 MLA-74 UML-491 ALA-10 MPD-75 In the amides marked with "*" there has been the introduction of a new asymmetric center, which of course doubles the number of isomers that is possible. In each case the resulting two optical forms were prepared separately, and evaluated separately as to their pharmacology. This listing is not intended to be thorough, but it is shown to suggest the amount of synthetic effort that has been made towards the exploring and understanding the high potency associated with those two remarkably important ethyl groups on the amide nitrogen of LSD. I have given the Sandoz code names, again, as far as I know them. Although none of these really warrant a dedicated recipe, there is sufficient animal and human pharmacology reported to justify listing them below as separate items. Most of these reports appeared in the mid-1950's but some studies are still being done and papers are published even today with new ideas but, sadly, only with animal pharmacology. I have been as guilty as the next person who has tried to mount all these compounds into a table with a "human potency" factor that compares them directly to LSD. This is an uncomfortable simplification. Here are the actual reported observations, and I'll let the reader provide his own potency index. LA-111, ergine, d-lysergamide. This is an active compound and has been established as a major component in morning glory seeds. It was assayed for human activity, by Albert Hofmann in self-trials back in 1947, well before this was known to be a natural compound. An i.m. administration of a 500 microgram dose led to a tired, dreamy state with an inability to maintain clear thoughts. After a short period of sleep, the effects were gone and normal baseline was recovered within five hours. Other observers have confirmed this clouding of consciousness leading to sleep. The epimer, inverted at C-8, is isoergine or d-isolysergamide, and is also a component of morning glory seeds. Hofmann tried a 2 milligram dose of this amide, and as with ergine, he experienced nothing but tiredness, apathy, and a feeling of emptiness. Both compounds are probably correctly dismissed as not being a contributor to the action of these seeds. It is important to note that ergine, as well as lysergic acid itself, is listed as a Schedule III drug in the Controlled Substances Act, as a depressant. This is, in all probability, a stratagem to control them as logical precursors to LSD. LAE-32, N-ethyllysergamide. Different people have observed and reported different effects, with different routes of administration. Subcutaneous administrations of from 500 to 750 micrograms have been said to produce a state of apathy and sedation. Clinical studies with dosages of 500 micrograms i.m. were felt to be less effective than the control use of 100 micrograms of LSD. And yet, oral doses of twice this amount, 1.6 milligrams, have been said to produce a short-lived LSD-like effect with none of these negatives. LPD-824, N-Pyrrolidyllysergamide. Five trials at a dosage of 800 micrograms orally led to the reporting of a fleeting effect that was similar to one tenth this amount of LSD. LSM-775, N-Morpholinyllysergamide. There are conflicting reports; one states that 75 micrograms is an effective dose, comparable to a similar dose of LSD, and the other stated that between 350 and 700 micrograms was needed to elicit this response, and that there were fewer signs of cardiovascular stimulation and peripheral toxicity. DAM-57, N,N-Dimethyllysergamide. This compound did induce autonomic disturbances at oral levels of some ten times the dosage required for LSD, presumably in the high hundreds of micrograms. There is some disagreement as to whether there were psychic changes observed. DAL, N,N-Diallyllysergamide. As the tartrate salt, there is at best a touch of sparkle seen at 600 micrograms orally, but there is a sedation also reported. It is certainly an order of magnitude less potent than LSD itself. UML-491, Methysergide, Sansert. This is the synthetic homologue of methergine (1-methyl) and is employed clinically as a treatment for migraine headaches. When the usual therapeutic dosage of two milligrams is scaled up by a factor of ten, there is a profound LSD-like response described by most subjects. A number of these ergot analogues from nature can be considered as potential precursors for the preparation of LSD. But here, there is a 1-methyl group that is effectively permanently attached, so it cannot play this role.
edical literature. A number of analogues of LSD have maintained the diethylamide group unchanged, but additions or changes have been made in the pyrrole ring.
ALD-52. 1-Acetyl-N,N-diethyllysergamide. This material has been explored in the 50-175 microgram range and there are a number of human trials reported, with varying conclusions. One found that there was less visual distortion than with LSD and it seems to produce less anxiety and was somewhat less potent than LSD. Another report claimed it was more effective in increasing blood pressure. Yet another could not tell them apart. ALD-52 just may have been the drug that was sold as "Orange Sunshine" during the "Summer of Love" in the late '60's. Or "Orange Sunshine" may have been, really, LSD. This was the focus of a fascinating trial where two defendants were accused of distributing LSD, whereas they claimed that it was ALD-52 which was not an illegal drug. The prosecution claimed that as it hydrolyses readily to LSD, for all intents and purposes it was LSD, and anyway, you had to go through the illegal LSD to get to ALD-52 by any of the known chemical syntheses. The defendants were found guilty. And yet, I do not know who has actually measured the speed or ease of that reaction. If ALD-52 hydrolyses so easily to LSD, and the body is indeed a hydrolytic instrument, then these two drugs should be absolutely equivalent in every particular, This is the ergot equivalent of the psilocybin to psilocin argument, except this is an acetamide rather than a phosphate ester. MLD-41. 1-Methyl-N,N-diethyllysergamide. The 1-methyl homologue of LSD is has more of somatic than sensory effect, has fewer visuals and is less well accepted than LSD, with the range of dosages being from 100 to 300 micrograms. This indicates that it is perhaps a third the potency of LSD which is in accord with both pupilary dilation and reflex action. However, the cardiovascular responses are actually increased. Besides being less potent than LSD, it appears to have a slower onset but it is equally long lived. There is cross-tolerance between MLD-41 and LSD. BOL-148. 2-Bromo-N,N-diethyllysergamide. This synthetic ergot derivative, along with its 1-methyl homologue MBL-61 (mentioned below) should be used as powerful tools for studying the mechanism of action of LSD in the human animal. It does not have LSD-like effects in man. At 6 to 10 milligrams orally, there are some mental changes noted. But in another study, 20 milligrams was administered a day to a subject for 7 days, and there were no reported effects. And yet it is as potent a serotonin agonist as is LSD. How can serotonin be argued as a neurotransmitter that is a major player in explaining the action of psychedelic drugs, when this compound is nearly without activity. There are some suggestions that an intravenous route may be more effective. I have heard of effects being noted at maybe a milligram and a short (2-3 hour) intoxication following 20 milligrams administered over a 20 minute period. I was involved many years ago in a study of radio-labelled BOL-148 which was made by the bromination of LSD. I was quite sure that the only radioactive material present was BOL-148, but there could well have been some unreacted LSD still present which would, of course, still be psychoactive. The synthesis is not clean -- I was tempted to make an entry for this compound if only to reproduce Albert Hofmann's original published experimental procedure. He reacted 13.2 grams of N-bromosuccinimide (in 400 mL dioxane, with 1.2 liters of dioxane containing 25 grams of LSD. This gave 11 grams of crude product which had to be recrystallized. The radioactive syntheses uses effectively elemental bromine, and gave yields of from 5 to 15%. Visualize that reaction! A warm flask containing over a quart of warm solvent in which there was maybe half a million doses of LSD. 1-Hydroxymethyl-LSD, 1-dimethylaminomethyl-LSD and 2-iodo-LSD. These three additional compounds are shown here because they were described in a synthetic flurry that followed the discovery the activity of LSD. But at the moment I know neither their internal Sandoz codes nor if they had ever been explored in man. This is a kind of frustrating catch-all entry, in that the long index will send you here, and once here you realize that nothing is known. Well, at least the compounds are known, and perhaps there is something in the Sandoz vaults that might be interesting. I do not have access to them. MBL-61. 2-Bromo-N,N-diethyl-1-methyllysergamide. This is the compound BOL-148 (mentioned above) with a methyl group attached to the 1-position of the indole ring (LSD has a hydrogen there). This would be an even more tantalizing challenge to the serotonin theory for central activity of the psychedelics, in that it is without any activity in man at an oral dose of 14 milligrams (similar to the inactivity of the BOL-61 compound, but it is some five times more potent as a serotonin agonist. With it, as with the iodinated analogue MIL, there are many examples of the compromising of scientific integrity in the quest for funds and recognition. Both compounds are as effective as LSD itself in displacing labelled LSD that is bound to the post-synaptic serotonin receptor sites in animal brains. But neither of them show any LSD-like activity. But both have been labelled with 11C or 122I to give positron emitting forms that can be administered to man and localized in a positron emission tomography instrument (a PET scanner). I was at a meeting of a NIDA study section a few years ago, where some one presented some findings with a group of subjects who were complaining of continuing mental problems allegedly due to LSD exposure. A chart was put up showing the outline of the brain showing the locations of the EEG foci that were observed in one of these subjects. Along side it was a PET scan showing the distribution of radioactive LSD in a subject. The purpose was to discuss the similarities and differences of the coordinates of electrical activity and radio-isotope concentration. I innocently asked what positron isotope had been used, as I did not know of any successful positron labelling of LSD. Carbon 11, I was told. Where in the molecule was the label incorporated, I asked. In the 1-position methyl group. It was finally acknowledged that the compound that had actually been used was 2-iodo-1-methyl-LSD, our MIL compound, which is quite a different world. A pharmacologist might say that they are similar in action (looking at serotonin, not psychedelic action), and a chemist might say they are of similar structure (looking at the upper 80% of the molecule. But they are different compounds. This is a most subtle form of deceit. It is, in fact, out and out dishonest, but it looks good up there on the screen at a lecture. Let me mention in passing, that there are three stereoisomers possible for d-LSD. There are d-iso-LSD, l-LSD, and l-iso-LSD. The inversion of the stereochemistry of the attached diethylcarboxyamido group of d-LSD gives the diastereoisomer (d-iso-LSD) which is a frequent synthetic impurity of d-LSD itself. The corresponding optical antipodes l-LSD and l-iso-LSD are also known and have been tasted. All three are completely inactive: d-iso-LSD shows no psychological changes at an oral dose of 4 milligrams; l-LSD none at up to 10 milligrams orally; and l-iso-LSD none at 500 micrograms orally. These dramatic decreases in potency show both the stereoselectivity of the native LSD molecule in producing its central effects, and the LSD-free purity of these isomers. The second major location of variations in the structure of LSD has been in the nature of the alkyl groups on the amide nitrogen atom. Some of these are Sandoz syntheses, some are from other research groups, and a few of them are found in nature. Some of these have been studied in man, and some have not. A few of the original clutch of Sandoz compounds have both 1-substituents and amide alkyl (R) group variations: indole--- amide nitrogen substituents --- R=R=R=code name -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -H -CH3 -CH3 -COCH3 -CH3 -H -CH3 -CH2CH3 -(CH2)2CH3 -CH(CH3)CH2OH -CH(CH3)CH2OH -(CH2)CH3 -CH(CH3)CH2CH2OH -(CH2)4CH3 -CH(CH3)CH2CH2CH3 -CH(CH2CH3)2 -(CH2)5CH3 -CH(CH3)CH2CH2CH2CH3 -(CH2)6CH3 -CH(CH3)CH2CH2CH2CH2CH3 -CH3 -CH2CH3 -(CH2)2CH3 -CH(CH3)2 -CH(CH3)CH2C6H5 -CH2CH3 -(CH2)2CH3 -(CH2)2CH3 -CH(CH3)2 -CH2CH=CH2 -(CH2)2CH3 -CH2CH2CH2CH2- -CH2CH=CHCH2- -CH2CH2CH2CH2CH2- -CH2CH2OCH2CH2- -CH2CH3 -CH(CH2CH3)CH2OH -COCH3 -CH2CH2CH2CH2- -H -H -H -H -H* -H -H* -H* -H -H* -H -H -H* -H -H* -CH3 -CH3 -CH3 -CH3 -CH3* -CH2CH3 -CH2CH3 -(CH2)2CH3 -CH(CH3)2 -CH2CH=CH2 -(CH2)3CH3 -H -H* -CH2CH3 LA-111 LAE-32 Ergonovine Methergine DAM-57 LAMP LSD-25 DAL LPD-824 LSM-775 MLA-74 UML-491 ALA-10 MPD-75 In the amides marked with "*" there has been the introduction of a new asymmetric center, which of course doubles the number of isomers that is possible. In each case the resulting two optical forms were prepared separately, and evaluated separately as to their pharmacology. This listing is not intended to be thorough, but it is shown to suggest the amount of synthetic effort that has been made towards the exploring and understanding the high potency associated with those two remarkably important ethyl groups on the amide nitrogen of LSD. I have given the Sandoz code names, again, as far as I know them. Although none of these really warrant a dedicated recipe, there is sufficient animal and human pharmacology reported to justify listing them below as separate items. Most of these reports appeared in the mid-1950's but some studies are still being done and papers are published even today with new ideas but, sadly, only with animal pharmacology. I have been as guilty as the next person who has tried to mount all these compounds into a table with a "human potency" factor that compares them directly to LSD. This is an uncomfortable simplification. Here are the actual reported observations, and I'll let the reader provide his own potency index. LA-111, ergine, d-lysergamide. This is an active compound and has been established as a major component in morning glory seeds. It was assayed for human activity, by Albert Hofmann in self-trials back in 1947, well before this was known to be a natural compound. An i.m. administration of a 500 microgram dose led to a tired, dreamy state with an inability to maintain clear thoughts. After a short period of sleep, the effects were gone and normal baseline was recovered within five hours. Other observers have confirmed this clouding of consciousness leading to sleep. The epimer, inverted at C-8, is isoergine or d-isolysergamide, and is also a component of morning glory seeds. Hofmann tried a 2 milligram dose of this amide, and as with ergine, he experienced nothing but tiredness, apathy, and a feeling of emptiness. Both compounds are probably correctly dismissed as not being a contributor to the action of these seeds. It is important to note that ergine, as well as lysergic acid itself, is listed as a Schedule III drug in the Controlled Substances Act, as a depressant. This is, in all probability, a stratagem to control them as logical precursors to LSD. LAE-32, N-ethyllysergamide. Different people have observed and reported different effects, with different routes of administration. Subcutaneous administrations of from 500 to 750 micrograms have been said to produce a state of apathy and sedation. Clinical studies with dosages of 500 micrograms i.m. were felt to be less effective than the control use of 100 micrograms of LSD. And yet, oral doses of twice this amount, 1.6 milligrams, have been said to produce a short-lived LSD-like effect with none of these negatives. LPD-824, N-Pyrrolidyllysergamide. Five trials at a dosage of 800 micrograms orally led to the reporting of a fleeting effect that was similar to one tenth this amount of LSD. LSM-775, N-Morpholinyllysergamide. There are conflicting reports; one states that 75 micrograms is an effective dose, comparable to a similar dose of LSD, and the other stated that between 350 and 700 micrograms was needed to elicit this response, and that there were fewer signs of cardiovascular stimulation and peripheral toxicity. DAM-57, N,N-Dimethyllysergamide. This compound did induce autonomic disturbances at oral levels of some ten times the dosage required for LSD, presumably in the high hundreds of micrograms. There is some disagreement as to whether there were psychic changes observed. DAL, N,N-Diallyllysergamide. As the tartrate salt, there is at best a touch of sparkle seen at 600 micrograms orally, but there is a sedation also reported. It is certainly an order of magnitude less potent than LSD itself. UML-491, Methysergide, Sansert. This is the synthetic homologue of methergine (1-methyl) and is employed clinically as a treatment for migraine headaches. When the usual therapeutic dosage of two milligrams is scaled up by a factor of ten, there is a profound LSD-like response described by most subjects. A number of these ergot analogues from nature can be considered as potential precursors for the preparation of LSD. But here, there is a 1-methyl group that is effectively permanently attached, so it cannot play this role.
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This is a link to shulgins LSD synth, with lots of notes on the switching out different amines
- By mycelium
This is a link to shulgins LSD synth, with lots of notes on the switching out different amines
