AN ALTERNATIVE ROUTE TO THE PREPARATION OF (3'-]5') METHYLENE ACETAL LINKED DINUCLEOSIDES AND TRINUCLEOSIDES

Reaction of deoxynucleoside 3'-O-(methylthiomethyl) acetals 1 with N-i odosuccinimide (NIS) and dibutyl phosphate furnished the corresponding 3'-O-(dibutoxyphosphoryloxy)methyl acetals 6. Condensation of the lat ter with appropriately protected deoxynucleoside acceptors 3, in the p resence of trimethylsilyl trifluoromethanesulfonate (TMSOTf), afforded in most cases the (3'-->5') methylene acetal linked d(B1 AND B2) dime rs 4. In addition, TMSOTf-promoted coupling of donor 6 (B1 = C(Bz)) wi th 3'-O-(methylthiomethyl)thymidine (8) yielded dimer 9. Reaction of 9 with NIS and dibutyl phosphate gave dimer 10, which was applied succe ssfully in the TMSOTf-assisted fusion with acceptors 3 (B2 = C(Bz) and A(Bz)), to afford the corresponding trimers d(C AND T AND C)11 and d( C AND T AND A)12.