title: Efficient syntheses of C(8)-aryl adducts of adenine and guanine formed by reaction of radical cation metabolites of carcinogenic polycyclic aromatic hydrocarbons with DNA.
abstract: The synthesis of the C(8)-aryl adducts of adenine and guanine formed by reaction of the radical cation metabolites of carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BP) and dibenzo[def,p]chrysene (DBC), with DNA is reported. The synthetic approach involves in the key step direct reaction of a PAH aldehyde with a di- or triamine precursor of a purine. The method is operationally simple, affords good yields of adducts, and is broad in its scope. The C(8)-aryl adducts of adenine and guanine derived from BP (6-BP-8-Ade and 6-BP-8-Gua) and DBC (10-DBC-8-Ade and 10-DBC-8-Gua) were synthesized in good yields by this method. Analogous C(8)-aryl adenine and guanine derivatives of other PAHs (anthracene, benz[a]anthracene, and chrysene) were also readily prepared via this approach. This method of synthesis is superior to the only method that is currently available. It entails direct reaction of short-lived PAH radical cations (generated electrochemically or chemically) with 2'-deoxyribonucleosides or the corresponding purine bases. It provides the adducts in low yields accompanied by complex mixtures of secondary products. An alternative synthesis that involves Pd-catalyzed Suzuki-Miyaura coupling of arylboronic acids with 8-bromopurine nucleosides was also investigated. Although the C(8)-purine adducts of PAHs, such as naphthalene, phenanthrene, pyrene, and chrysene, could be prepared by this method, analogous adducts of carcinogenic PAHs and other structurally related PAHs, e.g., anthracene, benz[a]anthracene, benzo[a]pyrene, and dibenzo[def,p]chrysene, could not be obtained. This difference was shown to be a consequence of the facility of competing hydrolytic deboronation of the corresponding arylboronic acids.
authors.affiliation: The Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Dai
authors.forename: Daiwang
authors.initials: D
authors.lastname: Xu
authors.forename: Keunpoong
authors.initials: K
authors.lastname: Lim
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Harvey
mesh_terms: D000225:Adenine / Q000737:chemistry*; D001564:Benzo(a)pyrene / Q000737:chemistry; D001897:Boronic Acids / Q000737:chemistry; D002273:Carcinogens / Q000737:chemistry*; D002412:Cations / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006147:Guanine / Q000737:chemistry*; D015394:Molecular Structure; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry*
chemical_list: D001897:Boronic Acids; D002273:Carcinogens; D002412:Cations; D005609:Free Radicals; D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene; D006147:Guanine; D004247:DNA; D000225:Adenine