O6-allyl protected deoxyguanosine adducts of polycyclic aromatic hydrocarbons as building blocks for the synthesis of oligonucleotides

We describe a synthetic strategy for the preparation of oligonucleotides using N-2-alkylated and O-6-allyl protected deoxyguanosine phosphoramidite building blocks derived from cis- and trans-opened (+/-)-7 beta ,8 alpha -dihydroxy-9 alpha, 10 alpha -epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene and (+/- )7 beta ,8 alpha -dihydroxy-9 beta, 10 beta -epoxy-7,8,9, 10-tetrahydrobenzo [a]pyrene and from trans-opened (+/-)-3 alpha ,4 beta -dihydroxy- 1 alpha ,2 alpha -epoxy-1,2,3,4-tetrahydrobenzo [c] phenanthrene. The appropriately blocked phosphoramidite building blocks were obtained as mixtures of the cis- and trans-opened diol epoxide adducts upon initial reaction of the diol epoxides with O-6-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine. Key to the present approach is the removal of the O-6-allyl protecting group utilizing a palladium catalyst prior to release of the constructed oligonucleotide with ammonia from the solid support. The methodology described enables a very convenient access to oligonucleotides containing cis- and trans-N-2-deoxyguanosine adducts of polycyclic aromatic hydrocarbons in different sequence contexts.