Highly diastereoselective synthesis of nucleoside adducts from the carcinogenic benzo[a]pyrene diol epoxide and a computational analysis.

A diastereoselective synthesis of the nucleoside adducts corresponding to a cis ring-opening of the carcinogen (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP DE-2) by 2'-deoxyadenosine and 2'-deoxyguanosine is described. The key intermediate (+/-)-10alpha-amino-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene was synthesized by a highly diastereoselective dihydroxylation wherein phenylboronic acid was a water surrogate. The resulting boronate ester was converted to a tetraol derivative in which two of the four hydroxyl groups (trans 7, 8) were protected as benzoate esters while the remaining two (cis 9, 10) were free.

Facile Pd-catalyzed cross-coupling of 2'-deoxyguanosine O6-arylsulfonates with arylboronic acids.

[reaction: see text]. The O6-(2-mesitylenesulfonyl) derivative of 2'-deoxyguanosine undergoes a facile palladium-mediated C-C cross-coupling with arylboronic acids. Demonstrating the general applicability of this method, the synthesis of a previously undescribed class of 2-amino-6-arylpurine 2'-deoxynucleosides has been accomplished.