Harmaline syntheses

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°. 

SYNTHESIS A stirred solution of 1.0 g harmaline hydrochloride in 25 mL H2O was covered with a pad of Argon, and there was added 0.1 g Pt02 followed by the dropwise addition of 0.4 g NaBH4 in 4.0 mL H2O over the course of 20 min. The pH was determined periodically and the reaction mixture was kept acidic during this... 

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... 

The structure of harman (II R = H) has been discussed already in connection with that of harmaline. Many additional syntheses of it and of its tetrahydro derivative have been recorded (39-44). Owing to the extremely active 2-position in the indole nucleus, cyclizations which yield quinolines from /3-phenethylamines proceed with greater ease from tryptamines, often yielding the tetrahydro bases under so-called physiological conditions (43, 44). A novel synthesis of harman depends upon... 

In order to explain the Na stimulation of ATP synthesis driven by a diffusion potential the presence of a Na /H antiporter was proposed [175]. In this artificial system the acidification of the cytoplasm, which occurs in response to electrogenic potassium efflux, could be prevented by the antiporter. Subsequently, Na /H antiporter activity has been demonstrated in both Methanobacterium thermoautotrophicum [176] and in Methanosarcina harden [108]. An important result of these studies was that the Na /H antiporter could be inhibited by amiloride and harmaline, which have been described as inhibitors of eucaryotic Na" /H" antiporters [177]. Using these inhibitors it has been shown that an active antiporter is essential for methanogenesis from H2/CO2 [176,178]. The antiporter also accepts Li instead of Na, since Li stimulates CH4 formation from H2/CO2 in the absence of Na [176]. In subsequent studies the use of amiloride and the more potent derivative ethyl-isopropylamiloride permitted the discrimination of primary and secondary Na potentials generated in partial reactions of the CO2 reduction pathway. 

Manske, R.H.F. et ai tChemical Society (Organic) 1-15,... 

Important work on alkaloids, particularly quinine, was done by Skraup (see p. 837) and his collaborator Wilhelm Konigs (Diilken, 22 April 1851-Munich, 15 December 1906), a pupil of Kekule and professor in the University of Munich. R. F. Pschorr, professor in the Technical High School, Char-lottenburg, worked on the synthesis of phenanthrene derivatives and their relation to morphine and other alkaloids. The important work on berberine and harmaline by W. H. Perkin jimr. and collaborators can only be mentioned. 

N-acyltryptamine if the harmaline system is desired and the Pictet-Spengler route, the tryptamine plus the appropriate aldehyde for a tetrahydro-j8-carboline (cf. p. 25). If a -carboline itself is required a tryptophan is substituted for the tryptamine in the latter synthesis and the product oxidized with chromic acid. 

---