Harman, 6-methoxy-1,2,3,4-tetrahydro · β-Carboline, 6-methoxy-1-methyl-1,2,3,4-tetrahydro · 6-Methoxy-1,2,3,4-tetrahydroharman · 10-Methoxy-3,4,5,6-tetrahydroharman · 6-Methoxy-1-methyl-1,2,3,4-tetrahydro-β-carboline · 1-Methylpinoline · Adrenoglomerulotropin · Aldosterone-stimulating hormone · McIsaac’s compound
SYNTHESIS: (from 2O5 over the course of 45 min. The solvent was removed under vacuum, and the residue treated with H2O, then made basic with dilute NaOH, and extracted with Et2O. Removal of the solvent from the pooled extracts and recrystallization of the residue from EtOH gave 1.0 g 6-methoxyharmalan with a mp 205–207 °C. High vacuum sublimation gave a product with a mp 208–209 °C. IR (in cm-1): 801, 824, 849, 990, 1031, 1076, 1182. MS (in m/z): Parent ion -1, parent ion 213, 214 (100%, 83%); 170 (22%); 195 (19%). This base can be dehydrogenated by heating 0.7 g with 3 g of Pd-black in a sealed tube for 30 min at 200 °C. The reaction mixture was treated with hot alcohol, filtered, and the filtrate stripped of solvent under vacuum. This gave 0.4 g 6-methoxyharman with a mp 266–267 °C from aqueous EtOH. The mp after recrystallization from MeOH is reported to be 273–274 °C. IR (in cm-1): 621, 698, 835, 1028, 1075, 1184. MS (in m/z): 197 (100%); parent ion 212 (66%); 169 (37%).
To a solution of 0.10 g 6-methoxyharmalan in 5 mL dilute HCl there was added 10 mg PtO2 followed by the dropwise addition of 40 mg NaBH4 dissolved in 1 mL of H2O. The solids were removed by filtration through paper, and the cream-colored filtrate made basic with 5% NaOH and extracted with 4×20 mL portions of CH2Cl2. The extracts were pooled, the solvent removed under vacuum, and the solid residue recrystallized from MeOH to give, after air drying to constant weight, 75 mg of free base 6-methoxytetrahydroharman (6-MeO-THH) as a white solid. IR (in cm-1): 797, 832, 975, 1112, 1121, 1148. MS (in m/z): 201 (100%); 186 (43%); parent ion 216 (38%); 172 (21%); 144 (16%).
(from 5-methoxytryptamine) A solution of 1.00 g 5-methoxytryptamine in 25 mL H2O was brought to a pH of 4 with 0.1 M HCl and put in a nitrogen placed under an N2 atmosphere. There was then added a solution of 1.5 g acetaldehyde in 15 mL of 85% aqueous EtOH. The solution was stirred for 2 days at room temperature, and then made basic and held at 0 °C allowing crystallization. There was thus obtained 175 mg (19%) of 6-methoxy-tetrahydroharman 6-methoxytetrahydroharman (6-MeO-THH) as a white solid, with a mp 160–161 °C. The literature also reports a mp of 224–226 °C.
EXTENSIONS AND COMMENTARY: I have decided to completely eliminate the dosage, duration and qualitative comments for this compound, and all related It still is. Rich and promising. It still is rich and promising. And still virgin. And it still is virgin.
Before the any particulars, some rather broad generals about nomenclature. This world of carbolines is a total bear as to the assignment of chemical names, so this is a logical place to talk about it. Many terms will be encountered. Some are totally trivial such as a specific compound that has been given a name from the binomial of the plant where it had been discovered, as in Leptactinia densiflora. Some are based on the completely general parent ring system itself, beta-carboline. Many compounds have many synonyms, and the carboline appendix in the back of this book would be a good place to save these names as you find them. For me, I look for middle territory. I look for two clues. The first is a sound that catches my attention immediately, the prefix, “harm-.” This demands that there is a methyl group in the molecule and that it is at the 1-position. The second clue is the vowel that follows the harm-. It will usually be an “a” or an “i” or occasionally and “o.” The harma- things have nothing on the aromatic ring, and the harmi- things have a 7-methoxy group there, and the harmo- things are usually phenolic, with an oxygen attachment there. And the numbering systems can be totally off the wall.
Let me try organize the “harm” chaos first, always with that methyl group at the C-1 position of the carboline ring. And the The second collection has a hydrogen atom there.
|indole sub.||aromatic (H0)||dihydro (H2)||tetrahydro (H4)|
|with a 1-methyl substituent|
|with a 1-hydrogen substituent|
Some minor stumbling blocks remain in this system. βC (β-carboline) has been called nor-harman, since it is harman without the methyl group. This is incorrect in theory in that the prefix “nor” implies that the lost group comes from a nitrogen. Incorrect, but common. Many additional synonyms and botanical locations are given in the carboline appendix. And throughout this discussion, I will totally ignore the chemically correct way of naming beta-carboline, which is
A brief comment on the numbering systems that can be found. The procedure used here and in the appendix starts counting at the carbon atom of the pyridine ring that is closest to the indole nitrogen. The pyridine nitrogen atom becomes two, and on around hitting every substitutable atom ending on the indole nitrogen as the 9-position. However, as usually in the older literature but still seen sometimes today, the indole nitrogen is the 1-position (as it still is when a structure is seen as an indole) and then every atom, substitutable or not, is numbered sequentially. This brings the 7-substitution identifier of
Back to the individual chemical stories. This commentary will cover the scatter of beta-carbolines that might play some major role in the human nervous system, other than the six 6-position oxygen can come directly from
6-Methoxy-tetrahydroharman 6-Methoxytetrahydroharman (6-MeO-THH) is the title chemical of this recipe. This particular β-carboline is a focal points of an ongoing controversy. To put all the cards directly on the table, this compound can in theory be made easily in the body and thus it could be present as a normal component in the brain. It has been synthesized by McIsaac, in Texas, under physiological conditions, with acetaldehyde and 5-methoxytryptamine. And, so the reasoning goes, if it can be made under these conditions in the laboratory, why not in the brain? He was completely convinced that it would be found some day to play an important role in mental health, just as he was convinced that it would prove to be a psychoactive compound. Perhaps it would be the product of some psychological trauma, or maybe be the source of such a trauma. He once told me (at a meeting years ago, over a quiet breakfast) that one of his ambitions was to assay the brains of people who were in all different kinds of mental states at the time of their deaths, and to correlate the carboline levels with that mental state. I asked him if he had personally tasted the material, and apparently he had not.
It is a component of the bark of the legume Arariba rubra (Sickingia rubra), native to the Bahia state in Brazil, as well as from the bark of Symplocus racemosa. This tree was introduced into Goa in the mid-nineteenth century, and from it has come a drug called Araroba powder (or Goa Powder, Brazil powder, or Ringworm powder). This turn of the century drug of commerce contains the non-nitrogenous anthracene Chrysarobin, isolated commercially from the closely related legume, Andira araroba (Vouacapoua araroba). It has been used in the treatment of ringworm and a number of skin diseases.
It is, however, a recognized component of the extracts of the passion flower Passiflora incarnata, but the much more plentiful inventory of flavinoids present in this marvelously named plant seem to be the agents that are responsible for its sedative properties. Again,
The positional isomer with the hydroxyl group at the 7-position,
About TiHKAL · info
This version of Book II of TiHKAL is based on the Erowid online version created by Bo Lawler with the help of Erowid, from content generously provided in electronic format by the Authors.
The Erowid online version does not always align precisely with the printed version. Text appears to have been inserted, deleted, or changed at various points. Where the two are seen to diverge both the Erowid and print versions are given. Sharp-eyed readers are encouraged to report novel discrepancies.
As with PiHKAL, I’ve again attempted to reproduce the typographic style of the printed edition. I’ve again made minor changes to some chemical names in line with current nomenclature practice. Typically the change is little more than expanding a prefix or setting it in italics. The history page has further details.
“At the present time, restrictive laws are in force in the United States and it is very difficult for researchers to abide by the regulations which govern efforts to obtain legal approval to do work with these compounds in human beings.“No one who is lacking legal authorization should attempt the synthesis of any of the compounds described in these files, with the intent to give them to man. To do so is to risk legal action which might lead to the tragic ruination of a life. It should also be noted that any person anywhere who experiments on himself, or on another human being, with any of the drugs described herein, without being familiar with that drug’s action and aware of the physical and/or mental disturbance or harm it might cause, is acting irresponsibly and immorally, whether or not he is doing so within the bounds of the law.”
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