Synthesis of 3 '-phosphate adducts of cyclopenta[cd]pyrene with deoxyguanosine via 3 '-H-phosphonate intermediates

P-32-postlabeling, a highly sensitive chromatographic technique used to det ect DNA adducts in vivo, requires synthetic chromatographic standards to de finitively identify stereochemical configurations of adducts. Herein is rep orted a versatile synthetic route to stereochemically pure deoxyguanosine-3 '-phosphate adducts of cyclopenta[cd]pyrene (CPP), a widespread environment al mutagenic and carcinogenic nonalternant PAH. The synthetic route, applic able to deoxyadenosine and other PAH nucleotide adducts, proceeds through a 3'-H-phosphonate intermediate which also serves as a valuable synthon for site-specifically modified oligomers. Stereochemically pure nucleotide addu cts of CPP with deoxyguanosine were obtained by condensation of racemic tra ns 3-amino-4-hydroxy-CPP with 2-fluoro-2'-deoxyinosine-3 '-H-phosphonate de rivatives followed by oxidation to the corresponding 3'-phosphate and subse quent separation of the diastereomers by reverse phase HPLC. The separated adducts were characterized by proton and phosphorus NMR as well as mass spe ctrometry.