Norharmane

Apart from the syntheses already quoted as of possible biological interest, mention must be made of a series which are primarily of chemical interest. Kermack, Perkin and Rob mson prepared norharman, i.e., /S-carboline (VII) by warming A-methylindole-2-carboxyacetalylamide (XVIII) with alcoholic hydrogen chloride, thereby converting it into 2-keto-l-methyl-2 3-dihydro-/S-carboline (XIX), which on distillation... 

The nomenclature used to describe the fused benzene-pyrrole-pyridine system of the compounds under discussion has been repeatedly modified, and the compounds have been numbered in an astonishing variety of ways since Perkin and Robinson introduced the name carboline for the ring system, which was encountered for the first time in the harmala alkaloids. In the earliest version of carboline nomenclature, the parent compound of the series, whose trivial name was norharman, was referred to as 4-carboline and numbered as in 1. Harmine (2) then became ll-methoxy-3-methyl-4-carboline. 

Chemical Abstracts), and a-carboline is sold commercially under the name 1-azacarbazole. The trivial norharman nomenclature, in conjunction with numbering as in 1 or as in 6, is still to be found in recent papers. Other systems of numbering, as well as some incorrect systems of nomenclature, are to be found and add to the confusion. 

Note that the plant elaborates a series of carboline alkaloids including 1-carbobutoxy-(3-carboline, N9-formylharman, 1 -carboethoxy- (3-carboline, 1-carbomethoxy- fl-carboline, perlolyrine, harman, and norharman (23). An interesting development would be to assess these alkaloids for central nervous activity. 

Poindexter, E., Carpenter, R. The isolation of harmane and norharmane from tobacco and cigarette smoke. Phytochemistry. 1 215, 1962. 

Structures 23, 24. Harman (82) and norharman (83) have been isolated from cigarette smoke (175), and Janiger and deRios (122) have suggested that some of the tobacco-induced altered states reported by South American Indians might be related to the cumulative effects of these beta-carbolines. 

Figure 13.7 Mutagenic and carcinogenic heterocyclic amines of the carboline group (a) AaC (2-amino-9//-p5Tido[2,3,-i)]indole), (b) norharman (9f/-pyrido[4,3-i)]indole), (c) Trp-P-1 (3-amino-l,4-dimethyl-57/-pyrido[4,3-/)]indole), (d) Glu-P-1 (2-amino-6-methyl-dipyrido[l,2-a 3, 2 -d]imidazole).

Indole alkaloids, such as harmane and norharmane, were also reported to be present in tobacco but in minute quantities. 

Siderhurst, M. S., James, D. M., Rithner, C. D Dick, D. L. and Bjostad, L. B. 2005. Isolation and characterization of norharmane from Reticulitermes termites (Isoptera Rhinotermitidae). Journal of Economic Enthomology, 98 1669-1678. 

Nagao, M., Yahagi, T. Sugimura, T. (1978) Differences in effects of norharman with various classes of chemical mutagens and amounts of S-9. Biochem. biophys. Res. Commun., 83, 373-378... 

PhIP 2-amino-l-methyl-6-phenylimidazo[4,5-/)]pyridine n T Vnh2 Nr" harman 1 -methyl-9H-pyrido[4,3-b]indole O7O ch3 norharman 9H-pyrido[4,3-b]indole v. L Jj... 

Fig. 4 (a) Polar extracts of fish pan fried and barbecued for 9 min. Pan frying at 200°C produced more MelQx (peak B) than barbecuing for the same time at 270°C (peak C). MelQx peak C (< 1 ng/g) illustrates the DL of the method. Online recorded UV spectra from MelQx peaks are shown at the right, (b) Polar and apolar extracts of fish barbecued per side at 270°C. These samples contained detectable PhIP in the polar extract (left) and AaC, norharman, and harman in the apolar extract (right). (From Ref. 177.)... 

Trp-P-2 (3-amino-l-methyl-5//-pyrido[4,3-h]indole), AaC (2-amino-9//-pyrido[2,3-bJindole), MeAaC (2-amino-3-methyl-9//-pyrido[2,3- ]indole), and PhIP (2-amino-1-methyl-6-phenyl-imidazo[4,5-h]pyridine) and two /3-carbolines comutagens harman (l-methyl-9//-pyrido[4,3-h]indole) and norharman (9//-pyrido[4,3-h]indole). The optimized SPE procedure for isolation and preconcentration comprises the use of diatomaceous earth, propylsulfonyl silica gel, and C18 cartridges to separate selectively the imidazopyridine and indolpyridine derivatives from those of... 

Suzuki J, Koyama T, Suzuki S. 1983. Mutagenicity of mono-nitrobenzene derivatives in the presence of norharman. Mutat Res 120 105-110. 

Some of these compounds have been detected upon thermal decomposition of certain foods, amino acids, and proteins. Significant amounts of compound (13), known as norharman, and its 9-methyl derivative, commonly called harman, have been found in tryptophan pyrolyzates. Similarly, cigarette smoke condensate has been found to contain significant amounts of both of these compounds <82JC331>. 

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