Harminic acid

A similar oxidative ring opening is reported to take place when 7-methoxy-l-styryl-j8-carboline is oxidized. The product, which was reported to be identical with harminic acid, is presumably the related compound 283 (R = CO2H or H). 

Azaindoles are nitrated readily by treatment with fuming nitric acid at 0°. In his early work, Fischer nitrated apoharmine, obtaining a high-melting crystalline compound, which reacted with methyl iodide and alkali, to give, presumedly, 3-nitro-6,7-dimethyl-6fl -6-azaindole. The stepwise decarboxylation of harminic acid gives a monocarboxylic acid, 7-methyl-6-azaindole-2-carboxylic acid, which was also nitrated. The position of nitration was not established in either case. 

Harmine, C13H12ON2, crystallises from methyl alcohol in colourless rhombic prisms, m.p, 266°, [a]D 0°. The hydrochloride, m.p. 269-5-270-5° (Chen ), nitrate, platinichloride, m.p. 264-6°, acid chromate and oxalate crystallise well. The salts show a deep blue fluorescence in dilute solution. Harmine behaves as a monoacidic base. It gives a methiodide, from which methylharmine, needles, m.p. 209°, may be prepared, and this in turn yields methylharmine methiodide. On demethylation harmine yields the phenolic base harmol, C12H10ON2, m.p. 321°.i ... 

In view of its possible interest as the mode of formation of harman, harmine and harmaline in plants, Kermack, Perkin and Robinson investigated the conversion of tryptophan (II) into harman (I) and nor-harman (IV). The latter is produced when tryptophan is condensed with formaldehyde in presence of dilute sulphuric acid and the product (III) oxidised by potassium dichromate. Harman is formed when formaldehyde in this process is replaced by acetaldehyde. 

The bromination of 7-methoxy-l-methyl-j8-carboline (harmine) was studied by Fischer. He obtained a compound, Ci3Hi2Br4N20, which he called tetrabromoharmine, by the action of bromine water on a dilute sulfuric acid solution of harmine. The bromination of harmine was reinvestigated by Hasenfratz, who found that two products (both hydrobromides) could be isolated when harmine was treated with bromine in aqueous acetic acid. The major component formed colorless needles and was called bromoharmine hydrobromide (free base colorless needles, m.p. 275°), while the product obtained in lesser amount was a canary-yellow dihydrate which was named isobromoharmine hydrobromide (free base colorless needles, m.p. 

Seven groups of these drugs can be separated based on their various chemical f structures (a) lysergic acid derivatives, of which lysergide (LSD) is the prototype (b) phenylethylamine derivatives, of which 3,4,5-trihydroxyphenylethylamine (mescaline) is the prototype (c) indolealkylamines, such as 4-phosphorodi-methyltryptamine (psilocybin) (d) other indolic derivatives, such as the harmine... 

Banisteriopsis caapi The primary hallucinogenic constituents of B. caapi are the jS-carbolines. These include harmaline, tetrahydroharmine, harmol, harmic acid methyl ester, harmic amide, acetyl norharmine, harmine A/-oxide, harmalinic acid, and ketotetrahydronorharmine (figure 9.8). B. rusbyana also contains DMT, as well as A/-methyltryptamine, 5-methoxy-N,/V-dimethyltryptamine, and 5-hydroxy-N,/V-dimethyltryptamine (bufotenin). /V-methyltetrahydro-jS-carboline is found in trace amounts. 

Anthranilic acid-derived Zygophyllaceae Peganum harmala Harmin... 

How can this enigma be answered Put away a sample of pure harmaline, with its spectral identification, onto the shelf for 50 or 100 years, and then re-analyze it Who knows, but what might be needed for this conversion is heat, or a bit of iron catalyst, or some unknown species of South American mold. Acid is certainly known to promote this oxidation. It would be very much worth while to answer this question because some, perhaps much, of the results of human pharmacological studies that involve harmaline as a metabolic poison, may be influenced by the independent action of harmine as a harmaline contaminant. 

Harmaline is dihydroharmine and is easily oxidized to harmine. The position of the one double bond in the pyridine ring is fixed by its synthesis from 2-acetyl-3-(/J-aminoethyl)-6-methoxyindole (IV) by warming in acid solution (35). Harmaline is therefore V. A number of later syntheses have been reported (28, 36, 37). A very recent one (38) achieved a synthesis in which the one double bond might have been... 

During their early investigations of harmine, Perkin and Robinson attempted a synthesis of what they thought to be isoharman. The 2-quinolone amide (74) was cyclized with phosphoryl chloride to a chloro compound (75), which gave 2.ff-pyrrolo[2,3-6]quinoline (76, R = H) with tin and hydrochloric acid, and its 3-methyl derivative (75, R = Me) with methylmagnesium iodide. The name quinindole ... 

Smythies s model is supported by evidence that 5HT and many of its analogs, including LSD-25, N,N-DMT, and harmine can bond to DNA, RNA, or both. The evidence for the binding of tryptamine and its analogs to nucleic acids is central both to an understanding of Smythies s model and also to our own hypothesis of drug action. It is quoted at length below ... 

We have chosen to present one such speculation. As noted in the discussion of bonding sites for indoles to nucleic acids, some compounds appear to bind better to DNA than to RNA. One such compound is harmine, and its affinity for DNA is not surprising in view of its previously mentioned similarity to proflavin. It is possible, therefore, that harmine or one of its analogs, such as 6-methoxytetrahydroharman, would exhibit a superior capability to bond to DNA if it were enabled to cross the membrane. Perhaps in the normal organism, the DNA is unintercalated by any compounds, or perhaps serotonin is the normal intercalator. When a hal-... 

The ionization constants of the first excited states of p-carboline and three of its derivatives - harmane. harmine, and 2-methylharmine - have been re-ported, and the fluorescence and phosphorescence spectra of harmine, harmaline, and 3-dehydroreserpines have been determined in neutral, acidic, and basic solution at 298 and 77 K. The photo-oxidation of 3-dehydroreserpines has also been examined in this work. The luminescence spectra of a series of indole alkaloids have also been reported by the same workers. The effect of pH on the absorption and fluorescence spectra of sanquinonine, a benzophenanthridine alkaloid, have been studied in detail. 

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