Pyrocoll

In total, 185 substances were found in the wing-sac liquid of male S. bilineata from a Costa Rican population. For a more detailed analysis the relative peak area of thirteen focus compounds was compared (Table 14.1). Of these nine were male-specific substances (indole, indol-3-carboxaldehyde, indole-3-carboxylic acid, 2-aminoacetophenon, anthranilic acid, SHJOH-dipyrrolofl -aT -dJpyrazine-5,10-dione (pyrocoll), indolo[2,l-b]quinazoline-6,12-dione (tryptanthrin), 2,6,10-trimethyl-3-oxo-6,10-dodecadienolide, and a compound C15H24O2 of unknown structure), three were fatty acids (tetradecanoic acid, hexadecanoic acid, and octadecanoic acid), and one a steroid (cholesterol). On average, the cumulative peak area of these substances made up 62.5 20.7% of the whole chromatogram area. 

Pyrolysis and smoke studies of amino acids indicate that they are potential precursors of several nitrogen heterocyclic ring systems found in tobacco smoke. Proline has been shown to be efficiently converted to pyrrole upon pyrolysis (3219, 3724) and in addition has been proposed as a possible precursor of pyrocoll (2593, 4336). y-Amino acids and dicarboxy-lic amino acids are capable, under pyrolytic conditions, of forming 2-pyrrolidones (1967, 3079) and by a similar mechanism, A-amino acids can form 2-piperidones (1967, 3079). A side effect of the pyrolysis of amino acids is the formation of hydrogen cyanide. 

In 1960, Mold et al. (2592) reported the isolation and identification of the tricyclic A-heterocyclic 5H, QH-dipyrrolo[l,2-fl r,2 -(i]pyrazine-5,10-dione (pyrocoll) V (Figure XVlI.E-3) from CSC and demonstrated its relationship to its precursor in tobacco, the amino acid proline. Obviously, pyrocoll is not an aza-arene but an amide. Rodgman and Cook (3279) reported the identification of indole, carbazole, and several alkylated indoles and car-bazoles in CSC and confirmed the presence of 5H, QH-dipyrrolo[l,2-fl r,2 -(i]pyrazine-5,10-dione (pyrocoll) V described previously by Mold et al. (2592). Rodgman and Cook also assessed previously reported biological studies on indole, 3-methylindole (skatole), and carbazole None was reported to be tumorigenic in laboratory animals [Hartwell (1544), Shubik and Hartwell (3664)]. 

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. 

Although not originally classified at the time as cooked food mutagens, several amino acid-derived iV-heterocyclic compounds were identified in cigarette smoke condensate (CSC) in the early 1960s 5//,10//-Dipyrrolo[l,2-a r,2 -(i] pyrazine-5,10-dione (pyrocoll) 1 by Mold et al. (2592) and 9H-pyrido[3,4-fc]indole (norharman) 11 and l-methyl-9-H-pyrido[3,4-fc ]indole (harman) 111 by Poindexter and Carpenter (2972) (Figure XVll.F-1). 

Proline is the precursor in tobacco of 57/,107/-dipyrrolo[l,2-fl r,2 -(i]pyrazine-5,10-dione (pyrocoll) 1 in tobacco smoke. Tryptophan is the major precursor in tobacco of 1-methyl-... 

Rodgman and Cook (3279) conflrmed the presence in CSC of 5//,10//-dipyrrolo[l,2-a r,2 -alkylated indoles and carbazoles. Rodgman and Cook (3279) also reviewed the previously reported biological studies on indole, 3-methylindole (skatole), and carbazole None of the three was reported to be tumorigenic. 

In a 1974 in-house report, a 1975 TCRC presentation, and a 1977 publication on their study of the water-soluble portion of CSC, Schumacher et al. (3553) reported the identifications of l-methyl-97/-pyrido[3,4-/>]indole (barman), 5H,10H-dipyrrolo[l,2-a r,2 -(f pyrazine-5,10-dione (pyrocoll), octahydro-5//,107/-dipyrrolo[l,2-a r,2 -]indole. 

Testa, A. and P. Testa Heterocyclic nitrogen compounds in tobacco smoke condensate. I. Lower members Pyrrole, indole, skatole, carbazole, pyrocoll CORESTA Inf. Bull. 1964(2) 7-10. 

The barrier irt phertartthrerte 215 (160 kj mol ) (X = OEt, R = Me) was 30 kJ mol higher thart irt the rtaphthalene analogue 214. Interestingly, the phenanthrene compound underwent spontaneous resolution. Lactonization resulted in racemization. Optically pure atropisomers were employed to prepare optically pure (S,S)- and (R,R)-pyrocoll derivatives 216 and 217. All these atropisomers were screened with success as catalysts in the ethylation of aldehydes by diethylzinc. 

Some pyrrole-2-carboxylic acids, treated with acetic anhydride, give pyrocolls (73), whilst suitable 3-carboxylic acids form s quinones (74). 

Streptomyces sp. AK409 Pyrocoll Arthrobacter strains. Filamentous fungi, pathogenic protozoa, human tumor cell lines Dieter et al. (2003)... 

Dieter, A., Hamm, A., Fiedler, H. R, Goodfellow, M., Mueller, W. E. G., Brun, R., Beil, W, Bringmarm, G. Pyrocoll, an antibiotic, antiparasitic and antitumor compound produced by a novel alkaliphilic Streptomyces strain. JAntibiot. 2003,56(7), 639-646. 

P. G. Sammes has dehydrogenated the iminoethers of piperazine-diones with 2,3-dichloro-5,6-dicyanobenzoquinone 243). Cyclo-L-Pro-L-Pro can be oxidized with this reagent directly to pyrocoll 243). The use of sulfur as oxidizing agent has been successful only with N-acetylated piperazinediones 242). 

Current attention should focus on the search for novel secondary metabolites and novel enzymes from Halophilic/alkaU-tolerant and thermophilic actinobacteria from extreme environments. Novel alkaliphilic actinobacteria Nocardiopsis alkaliphUa, Nocardiopsis metallicus and Bogoriella caseilytica are a valuable source of novel products of industrial interest, including enzymes and antimicrobial agents (Mitsuiki et al., 2002 Tsujibo et al., 2003). Pyrocoll, an antibiotic compound, was recently detected in a novel alkaliphilic Streptomyces strain (Dietera et al., 2003). 

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