Preparation of Deoxynucleosides, Deoxynucleotides and Oligodeoxynucleotides Bearing Adducts of PAH Diol Epoxides at the N⁶ Position of Adenine

Abstract

Oligonucleotides bearing adducts of the diol epoxides of benzo[a]pyrene and other polycyclic aromatic hydrocarbons on the exocyclic amino group of adenine have been prepared in a regio and stereospecific manner. The strategy involves reversal of the electrophile-nucleophile relationship; the PAH is linked to the adenine nucleus via condensation of an aminotriol (derived from the diol epoxide) with 6−fluoropurine deoxyribonucleoside. This condensation is carried out after the fluoro nucleoside has been incorporated into the oligonucleotide, but while the oligomer is still immobilized on the solid matrix. The diastereomeric oligomers derived from (±)−anti−BPDE are readily separable by HPLC, thus circumventing the need for individual enantiomers of the diol epoxide.

Key Words:

• PAH adducts
• Oligonucleotides
• post-oligomerization strategy
• 6-fluoro-purine deoxyribonucleoside
• BPDE
• PAH aminotriols