A new and efficient method is described for the synthesis in gram quantities of the benzo[a]pyrene (B[a]P) metabolic adducts of 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) substituted, respectively, at the N(2)- and N(6)- positions. When the racemic form of the tris(benzoyloxy)amine 5 (related to the notoriously carcinogenic epoxydiol 2) is coupled with the bromoinosine derivative 6 by means of a Buchwald-Hartwig reaction, the expected pair of diastereomers, 7 and 8, is obtained in high (combined) yield. Selective deblocking of this mixture then gave cleanly the pair of diastereomers 9. These were used in the synthesis of a series of DNA oligomers via their 5'-O-DMT-3'-O-phosphoramidites (10) using standard automated methods. Coupling efficiencies were 94-98% at the point of introduction of the xeno-2'-deoxynucleoside, and in all cases the mixtures of the two diastereomeric oligomers (DMT-off stage) were easily separated by HPLC. By a similar sequence of reactions beginning with 5 and the protected 6-bromopurine 2'-deoxynucleoside 11, it was possible with equal efficiency to introduce the N(6)-modified diastereomers (16) of dA into oligomeric DNA. Circular dichroism measurements were used to establish the fundamental configurations at the xeno-2'-deoxynucleoside site for each of the oligomers. Mass spectral data in both the dG and the dA series confirmed the presence of the xeno-2'-deoxynucleoside in the oligomers. This was complemented by enzymatic degradation of one of the oligomers from each of the series. In both of these cases, after HPLC separation, circular dichroism measurements on the reisolated xenonucleoside also confirmed its presence in the oligomer.