Synthesis of 13C2-benzo[a]pyrene and its 7,8-dihydrodiol and 7,8-dione implicated as carcinogenic metabolites

Ran, Chongzhao; Xu, Dongxin; Dai, Qing; Penning, T.M.; Blair, Ian A.; Harvey, Ronald G.

doi:10.1016/j.tetlet.2008.05.033

Cited by 17 publications

(13 citation statements)

References 23 publications

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“…31,32 2-Bromobenzene-1,3-dialdehyde ( 15 ) was synthesized by the reported method,31 and Suzuki-Miyaura coupling of 15 with the boronate ester ( 3 ) catalyzed by Pd(PPh 3 ) 4 furnished the dialdehyde adduct ( 16 ). Double Wittig reaction of 16 with (methoxymethylene)triphenylphosphine (CH 3 OCH=PPh 3 )24 provided the di(methoxyvinyl) derivative ( 17 ) as a mixture of E - and Z -isomers. Acid-catalyzed cyclization of 17 furnished 9-methoxybenzo[ α ]pyrene, and demethylation with BBr 3 gave 9-HO-BP.…”

Section: Resultsmentioning

confidence: 99%

“…An efficient synthesis of 13 C 2 -BP from was recently reported 24. Direct synthesis of 6-HO-BP from BP was accomplished via initial Vilsmeier-Haack reaction of BP with POCl 3 and DMF to furnish 8-formylbenzo[ a ]pyrene ( 23 ) (Scheme 4).…”

Section: Resultsmentioning

confidence: 99%

“…In this connection, we recently reported syntheses of 13 C 2 -BP, 13 C 2 -BP 7,8-diol, 13 C 2 -BP 7,8-dione, and 13 C 2 -8-HO-BP 24. We now report improved new syntheses of the principal phenol and quinone isomers of BP formed in its metabolism in human bronchoalveolar H358 cells 21.…”

Section: Introductionmentioning

confidence: 84%

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Synthesis of Phenol and Quinone Metabolites of Benzo[a]pyrene, a Carcinogenic Component of Tobacco Smoke Implicated in Lung Cancer

Penning

Blair

et al. 2008

J. Org. Chem.

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Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced in the combustion of organic matter. PAHs are present in automobile exhaust and tobacco smoke, and they have recently been designated as human carcinogens. Current evidence indicates that PAHs are activated enzymatically to mutagenic metabolites that interact with DNA. There is evidence for three pathways of activation, the diol epoxide path, the radical-cation path, and the quinone path. The relative importance of these paths for human lung cancer has not been established. We now report syntheses of the principal phenol and quinone isomers of the prototype PAH carcinogen benzo[a]pyrene (BP) that are known or are suspected to be formed as metabolites of BP in human bronchoalveolar cells. The methods of synthesis were designed to be adaptable to preparation of the 13C-labelled analogues of the BP metabolites. These compounds are needed as standards for sensitive LC-MS/MS methods for analysis of BP metabolites formed in lung cells. Efficient novel syntheses of the 1-, 3-, 6-, 9-, and 12-BP phenols, and the BP 1,6-, 3,6-, 6,12-, and 9,10-quinones are now reported. The syntheses of the BP phenols (except 6-HO-BP) involve in the key steps Pd-catalyzed Suzuki-Miyaura cross-coupling of a naphthalene boronate ester with a substituted aryl bromide or triflate ester. The BP quinones were synthesized from the corresponding BP phenols by direct oxidation with the hypervalent iodine reagents IBX or TBI. These reagents exhibited different regiospecificities. IBX oxidation of the 7- and 9- BP phenols provided the ortho-quinone isomers (BP 7,8-, and 9.10-dione), whereas TBI oxidation of the 1-, 3-, and 12-BP phenols furnished BP quinone isomers with carbonyl functions in separate rings (BP 1,6-, 3,6-, and 6,12-dione).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Synthesis of Phenol and Quinone Metabolites of Benzo[a]pyrene, a Carcinogenic Component of Tobacco Smoke Implicated in Lung Cancer

Penning

Blair

et al. 2008

J. Org. Chem.

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“…16 Benzo[ a ]-pyren-8-ol was synthesized by the published method. 14a Benzo[ a ]pyren-7-ol ( 42b ) was synthesized from 9,10-dihydrobenzo[ a ]pyrene -7(8H)-one ( 40 ) by conversion to the enol acetate ( 41 ), dehydrogenation with o -chloranil, and hydrolysis (Scheme 3) by the published procedure. 22 Benzo[ a ]pyren-10-ol ( 46b ) was synthesized from 40 by the sequence depicted in Scheme 3.…”

Section: Methodsmentioning

confidence: 99%

“…12 Its use for oxidation of simple phenols to ortho -quinones has been described, 13 and we reported several examples of IBX oxidation of PAPs to the corresponding ortho -PAQs. 14 Another potentially useful hypervalent iodine reagent is bis(trifluoro-acetoxy)iodobenzene [(CF 3 CO 2 ) 2 IC 6 H 5 ] (BTI). Oxidation of several 1-naphthol derivatives by BTI was reported to furnish para -naphthoquinones.…”

Section: Introductionmentioning

confidence: 99%

Regiospecific oxidation of polycyclic aromatic phenols to quinones by hypervalent iodine reagents

Duan

et al. 2010

Tetrahedron

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The hypervalent iodine reagents o-iodoxybenzoic acid (IBX) and bis(trifluoro-acetoxy)iodobenzene (BTI) are shown to be general reagents for regio-controlled oxidation of polycyclic aromatic phenols (PAPs) to specific isomers (ortho, para, or remote) of polycyclic aromatic quinones (PAQs). The oxidations of a series of PAPs with IBX take place under mild conditions to furnish the corresponding ortho-PAQs. In contrast, oxidations of the same series of PAPs with BTI exhibit variable regiospecificity, affording para-PAQs where structurally feasible and ortho-PAQs or remote PAQ isomers in other cases. The structures of the specific PAQ isomers formed are predictable on the basis of the inherent regioselectivities of the hypervalent iodine reagents in combination with the structural requirements of the phenol precursors. IBX and BTI are recommended as the preferred reagents for regio-controlled oxidation of PAPs to PAQs.

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2‐Iodoxybenzoesäure – ein einfaches Oxidationsmittel mit einer Vielfalt an Anwendungsmöglichkeiten

Duschek

Kirsch

2011

Angewandte Chemie

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Seit seiner Entdeckung durch Christoph Hartmann und Victor Meyer im Jahr 1893 hat sich 2‐Iodoxybenzoesäure (IBX) zu einem geradezu ubiquitär einsetzbaren Oxidationsmittel entwickelt. Insbesondere in den vergangenen zehn Jahren wurde eine Vielzahl von Anwendungsmöglichkeiten beschrieben, die weit über die einfache Oxidation von Alkoholen hinausgehen. Dieser Aufsatz behandelt das Potenzial von IBX in der Synthese, wobei insbesondere unerwartete Reaktivitäten und moderne Anwendungen im Mittelpunkt der Diskussion stehen.

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Synthesis of 13C2-benzo[a]pyrene and its 7,8-dihydrodiol and 7,8-dione implicated as carcinogenic metabolites

Cited by 17 publications

References 23 publications

Synthesis of Phenol and Quinone Metabolites of Benzo[a]pyrene, a Carcinogenic Component of Tobacco Smoke Implicated in Lung Cancer

Synthesis of Phenol and Quinone Metabolites of Benzo[a]pyrene, a Carcinogenic Component of Tobacco Smoke Implicated in Lung Cancer

Regiospecific oxidation of polycyclic aromatic phenols to quinones by hypervalent iodine reagents

2‐Iodoxybenzoesäure – ein einfaches Oxidationsmittel mit einer Vielfalt an Anwendungsmöglichkeiten

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