2.8.2 Simple β-Carboline Alkaloids
The alkaloids based on the β-carboline ring system obviously suggest the formation of a new sixmembered heterocyclic ring employing the ethylamine side-chain present in tryptamine exactly in the same manner to the evolution of tetrahydroisoquinoline alkaloids (see Section 2.7.2). The exact mechanism whereby the above rearrangement is accomplished may be explained by virtue of the fact that C-2 of the indole nucleus is nucleophilic due to the adjacent nitrogen atom. Therefore, C-2 can conveniently participate in a Mannich/Pictet-Spengler type reaction, thereby enabling it to attack a Schiff base produced from tryptamine and either an aldehyde (or keto acid) as given below:
It has been observed that relatively simpler structures make use of keto-acids, such as: harman, harmaline, harmine and elaeagnine. These alkaloids shall be treated individually in the sections that follow.
Interestingly, the comparatively complex carbolines, for instance: the terpenoid indole alkaloids e.g., ajmaline are usually generated by the help of a pathway that specifically utilize an aldehyde, such as: secologanin. This particular section shall be dealt with separately under Section 7.2.8.3.
A. Harman
Synonyms Aribine; Loturine; Passiflorin; 2-Methyl-b-carboline; 3-Methyl-4-carboline;
Biological Sources It is obtained from the bark fruit of Passiflora incarnata L. (Passifloraceae) (May pop, Passion flower); seed of Peganum harmala L. (Rutaceae) (Harmel, Syrian Rue, African Rue), bark of Sickingia rubra (Mart.) K. Schum. (Arariba rubra Mart.), (Rubiaceae); and bark of Symplocus racemosa Roxb. (Symplocaceae).
Chemical Structure
1-Methyl-9H-pyrido [3, 4, b] indole; (C12 H10 N2).
Isolation Poindexter and Carpenter* isolated this alkaloid from the cigarette smoke.
Characteristic Features
1. It is obtained as orthorhombic crystals from heptane and cyclohexane having mp 237-238°C.
2. It has a bitter taste.
3. It exhibits distinct bright blue fluorescence in uv light.
4. It pKa’s are 7.37 and 144.6.
5. It has uvmax (methanol): 234, 287, 347 nm (log ε 4.57, 4.21, 3.66).
6. It is practically insoluble in water and freely soluble in dilute acids.
Identification Test Harman Hydrochloride (C12H10N2.HCl) It is obtained as rosettes of needles from a mixture of ethanol + 20% HCl in water which sublimes at 120-130°C.
Uses It is a narcotic hallucinogen.
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* Poindexter and Corpenter, Chem. & Ind. (London), 1962, 176.
B. Harmaline
Synonyms Harmidine; Harmalol Methyl Ether; O-Methyl-harmalol; 3, 4-Dihydroharmine;
Biological Sources It is obtained from the seeds of Peganum harmala L. (Zugophyllaceae); and Banisteria cappi Spruce (Malpighiaceae). It is also obtained from the fruit of Passiflora incarnata L. (Passifloraceae) (Passionflower, Maypop).
Chemical Structure
4, 9-Dihydro-7-methoxy-1-methyl-3H-pyridol [3, 4,-β] indole; (C13H14N2O).
Characteristic Features
1. It is obtained as orthorhombic bipyramidal prisms, or tablets from methanol; and as rhombic octahedra from ethanol having the same mp 229-231°C.
2. Its solutions give a blue fluorescence.
3. Its dissociation constant pKa 4.2.
4. It has uvmax (methanol): 218, 260, 376 nm (log ε 4.27, 3.90 and 4.02)
5. It is found to be slightly soluble in water, ethanol, ether; and very soluble in dilute acids and hot ethanol.
Identification Tests Harmaline forms definite derivatives as shown below:
1. Harmaline Hydrochloride Dihydrate (C13H14N2O.HCl.2H2O): It is obtained as slender, yellow needles that are found to be moderately soluble in ethanol and water.
2. N-Acetylharmaline: It is obtained as needles having mp 204-205°C.
Uses
1. It is recognized as a narcotic hallucinogen.
2. It is used as a CNS-stimulant.
C. Harmine
Synonyms Telepathine; Leucoharmine; Yageine; Banisterine;
Biological Sources It is obtained from the seeds of Peganum harmala L. (Zygophyllaceae); Banisteria caapi Spruce. (Malpighiaceae); and Banisteriopsis inebrians Morton. (Malpighiaceae). It is also obtained from the fruit of Passiflora incarnata L. (Passifloraceae).
Chemical Structure
7-Methoxy-1-methyl-9H-pyrido [3, 4-β] indole; (C13H12N2O).
Isolation Harmin may be isolated from the seeds of Peganum harmala L. (Zygophyllaceae) by the method suggested by Reinhard et al.
Characteristic Features
1. It is obtained as slender, orthorhombic prisms from methanol having mp 261°C (decomposition).
2. It sublimes and has pKa value of 7.70.
3. It as uvmax (methanol): 241, 301, 336 nm (log ε 4.61, 4.21, 3.69).
4. It is found to be slightly soluble in water, ethanol, ether and chloroform.
Identification Tests
Harmine Hydrochloride Dihydrate (C13H12N2O.HCl.2H2O) It is obtained as crystals having mp 262°C (decomposition), but when anhydrous mp 321°C (decomposition), but when anhydrous mp 321°C. The aqueous solution exhibits a distinct blue fluorescence. It is found to be soluble in 40 parts of water and freely soluble in hot water.
Uses It finds its usage as a CNS-stimulant and also as a narcotic hallucinogen.
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* Rainhard et al. Phytochemistry, 7, 503, (1968).
D. Elaeagnine
Biological Source It is obtained from the bark of Elaeagnus angustifolia Linn., (Synonyms: E. hortensis Bieb.) (Elaeagnaceae).
Chemical Structure
Biosynthesis of Elaeagnine, Harman, Harmaline and Harmine The various steps involved in the biosynthesis of the above mentioned four alkaloids are briefly summarized as under:
1. Tryptamine and acetyl carboxylic acid (i.e., keto acid) undergoes a Mannich-like reaction to yield a β-carboline carboxylic acid, which on oxidative decarboxylation gives rise to 1-methyl β-carboline.
2. The resulting product on subsequent reduction gives rise to the alkaloid elaeagnine.
3. The 1-methyl β-carboline upon mild oxidation yields the alkaloids harman with the elimination of a mole of water from the 6-membered heterocyclic nucleus.
4. The 1-methyl β-carboline upon hydroxylation followed by methylation produces harmaline.
5. Harmaline on further oxidation generates harmine by the loss of a mole of water from the 6-membered pyridine ring at C-3 and C-4 positions.
The these steps are sequentially arranged in the following course of reactions:
