SYNTHESIS OF ADDUCTS FORMED BY IODINE OXIDATION OF AROMATIC-HYDROCARBONS IN THE PRESENCE OF DEOXYRIBONUCLEOSIDES AND NUCLEOBASES

Polycyclic aromatic hydrocarbons (PAH) undergo two main pathways of me tabolic activation related to the initiation of tumors: one-electron o xidation to give radical cations and monooxygenation to yield bay-regi on diol epoxides. Synthesis of standard adducts is essential for ident ifying biologically formed adducts. Until recently, radical cation add ucts were synthesized by oxidation of the PAH in an electrochemical ap paratus, not readily available in many organic chemistry laboratories. We have developed a convenient and efficient method for synthesizing PAH-nucleoside adducts by using It as the oxidant. Adducts of benzo[a] pyrene (BP), dibenzo[a,l]pyrene (DB[a,l]P), and 7,12-dimethylbenz[a]an thracene were synthesized with deoxyguanosine (dG), deoxyadehosine, gu anine (Gua), or adenine in either Me2SO or dimethylformamide (DMF) wit h or without AgClO4. When, for example, the potent carcinogen BP was d issolved in DMF in the presence of 3 equiv of I-2, 5 equiv of dG, and 1 equiv of AgClO4, 45% of the BP was converted to BP-6-N7Gua. When BP was placed under the same reaction conditions in the absence of AgClO4 , the extent of formation of BP-6-N7Gua decreased to 30%. When the pot ent carcinogen DB[a,l]P was dissolved in DMF in the presence of 3 equi v of It, 5 equiv of dG, and 1 equiv of AgClO4, 43% of the DB[a,l]P was converted to DB[a,l]P-10-N7Gua. In the more polar solvent Me2SO under the same reaction conditions, however, the yield of DB[a,l]P-10-N7Gua was only 20%. Synthesis of adducts with the oxidant It is more conven ient and, in some cases, more efficient than synthesis by electrochemi cal oxidation. This method simplifies the synthesis of PAH-nucleoside and nucleobase adducts that are essential for studying biologically fo rmed PAH-DNA adducts.