Synthesis of cis adducts of cyclopenta[cd]pyrene with deoxyguanosine and deoxyadenosine

Recent analysis of DNA adducts of cyclopenta[cd]pyrene (CPP) formed in vitr o by reaction of CPP-3,4-oxide, with calf thymus DNA, suggested ring openin g of the enantiomeric 3,4-epoxide predominantly by cis addition. We describ e herein the chemical synthesis of DNA adducts resulting from benzylic cis ring opening of CPP-3,4-oxide by the exocyclic amino group of 2'-deoxyguano sine (dc) and 2'-deoxyadenosine (dA). The methodology involves synthesis of cis-3,4-dihydro-3-amino-4-hydroxycyclopenta [cd] pyrene followed by its co upling with appropriately protected halopurinedeoxyribose intermediates. Th e diastereomeric mixture of products resulted in the coupling reaction was separated by HPLC and characterized by H-1 NMR and MS analysis. Co-chromato graphy of the synthetic standards with in vitro adducts confirmed the ident ity and the stereochemical preference of the CPP-DNA adducts.