Harmaline

Harderian gland porphyrins in, 4, 382 Harderoporphyrin, 4, 382 Harmala alkaloids, 4, 529 Harmaline... 

On reduction harmaline yields tetrahydroharmine, C13HJ5ON2, m.p. 199°, and on gentle oxidation is converted into harmine. ... 

Constitution of Harmine and Harmaline. Harmaline is a dihydro-harmine. Both bases on reduction yield tetrahydroharmine and in both the single oxygen atom is present as methoxyl. Knowledge of the constitution of the two alkaloids is mainly due to the work of O. Fischer and his colleagues, and more recently to the researches of Perkin and Robinson. 

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. 

Since 1921 much work has been done to confirm the formula for harmine and that provisionally assigned to harmaline, both by synthetic methods and by reactions to explore and explain peculiarities in the... 

Of,the two other possible formulas for harmaline with the chain CHa C. NH. CHa. CHj— or —CHMe. NH. CH CH— in place of —CMe N. CH. CH — in positions 2 to 5, only the first is consistent with this synthesis, and, as work on methyl- and acetyl-harmaline (p. 493) has shown, this form is assumed with difficulty. 

Spath and Lederer have published a simplified synthesis of harmaline consisting in treating the acetyl derivative of 6-methoxytryptamine (XXIX) with phosphorus pentoxide in boiling xylene, the harmaline thus produced being converted into harmine by catalytic dehydrogenation at 200°. 

Non-oxidative conversion of a tetrahydro-)8-carboline into a 3,4-dihydro derivative has also been described. Dehydration of 1-hydroxymethyl-1,2,3,4-tetrahydro-j8-carboline (146) yielded 1-methyl-3,4-dihydro-j8-carboline (135). Harmaline and l-methyl-3,4-dihydro-j8-carboline-3-carboxylic acid were obtained in an analogous manner. ... 

Nitration of quinindoline gave the expected 9-nitro derivative (261). A single mononitro compound was formed from the 3,4-dihydro-jS-carboline, harmaline this was 6-nitroharmaline, since on oxidation it yielded 3-nitro-4-methoxybenzoic acid. 

In the course of structural investigations of a number of jS-carboline alkaloids, reactions leading to ring cleavage have been encountered. Oxidation of harmine (271) and of harmaline... 

Finally, mention should be made of the addition of nucleophilic reagents to the 1-position of 3,4-dihydro-j8-carbolines, Cyanide has been reported to yield adducts with harmaline, 6-nitroharm-aline, and 2-methylharmalinium salt similarly, hydroxylamine forms adducts with harmaline, 3,4-dihydro-j8-carboline (307 R = H), and l-phenyl-3,4-dihydro-)S-carboline (307 R =... 

Quaternization with alkyl halides of 3,4-dihydro-jS-carboline and its derivatives takes place at the pyr-N. Quaternary 3,4-dihydro-j8-carbolinium salts (309) derived from harmaline, 3,4-dihydro-j8-carboline, 6-methoxy-3,4-dihydro-j8-carboline, and 1 -methyl-3,4-dihydro-j8-carboline have been described. Further... 

The Eschweiler reaction (formaldehyde and formic acid) has been used for the pyr-A-methylation of l-methyl-l,2,3,4-tetrahydro-j8-carboline, as has formaldehyde and hydrogen in the presence of Raney nickel. Tetrahydroharmine has been reported to react with benzaldehyde to yield a condensation product, C33H36N403, which is presumably a pyr-iV-substituted derivative (318). It is not known whether a similar condensation product of benzaldehyde with harm-aline is a C- or V-substituted derivative of harmaline. Conden-... 

It has been postulated that harmaline itself may under certain conditions consist of an equilibrium mixture of the isomeric structures 122 and 441, with the former strongly predominating . Both forms are regarded as existing in equilibrium with the harmalinium cation (440), from which the former may be derived by deprotonation at the... 

These authors formulated the major steps in the biogenesis of the harmala bases as a condensation of a tryptamine derivative (460) with acetaldehyde to yield a l,2,3,4-tetrahydro-)3-carboline (461), which on oxidation in two stages would give harmaline (462 R = OCH3) and then harmine (463 R = OCH3). 

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