Norharman discussion

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. 

In his 1968 review of tobacco and tobacco smoke composition, Stedman (3797) discussed the identification of tumorigenic A-heterocyclic compounds [dibenz[fl,/t]acridine, dibenz[fl, ]acridine, and 7//-dibenzo[c, carbazole] reported by Van Duuren et al. (4027), as well as the identification of the following A-heterocyclic compounds 5//,10//-dipyrrolo[l,2-fl T,2 -(i]pyrazine-5,10-dione (pyrocoll), 9//-pyrido[3,4-fc] indole (norharman), l-methyl-9/f-pyrido[3,4-fc]indole (harman), and 9//-pyrido[2,3-fc]indole. 

In his early 1970s outline of recent research on tobacco and tobacco smoke composition, Wakeham (4103) noted the reported presence of 9//-pyrido[3,4- ]indole (norharman) and l-methyl-9//-pyrido[3,4-fc]indole (harman) in cigarette smoke and discussed their possible formation by reaction of tryptophan and an aldehyde. As noted by Rodgman (3253a), the structure of the aldehyde reacting with tryptophan ultimately dictates the structure of alkylated norharmans found in CSC (see Table XVH.E-2). 

Rodgman also discussed the already identified and other possible theoretical relationships (Figure XVII.F-5) between tryptophan XX and 9//-pyrido[3,4-( ]indole (norharman) II its methyl homolog l-methyl-9//-pyrido[3,4-fc]indole (harman) III and other substituted norharmans VI, R = C2H5, CH3CH=CH, and -C4H9, the tryptophan pyrolysis products 3-amino-1,4-dimethyl-5/7-pyrido-[4,3-( Jindole (Trp-P-1) IV and 3-amino-l-methyl-5//-pyrido[4,3-( ] indole (Trp-P-2) V the alkyl- and dialkyl-indoles indole-... 

In the 1982 Snrgeon General report (4010), 9//-pyrido[3,4-f>]indole (norharman) and l-methyl-9//-pyrido[3,4-f>]mdole (harman) were classified as toxic and tnmorigenic agents of cigarette smoke in amonnts of 3.2 to 8.1 xg/cig and 1.1 to 3.1 pg/cig, respectively, in cigarette MSS. None of the other mutagenic A/-heterocyclic amines in tobacco smoke was discussed. 

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