C-3 '-branched thymidines as precursors for the selective generation of C-3 '-nucleoside radicals

C-3'-nucleoside radicals can be generated via Norrish type I photocleavage of C-3'-acyl nucleoside derivatives. In monomer experiments employing C-3'- acylthymidine derivatives 2 and 3, a 1:1 mixture of isomers of the H-abstra ction products was obtained when the photolysis was carried out in the pres ence of a hydrogen donor. Derivatives 2 were synthesized by an approach whi ch involves the formation of a silyl-protected cyanohydrin, which is subseq uently alkylated with organolithium reagents, followed by hydrolysis. Deriv atives 3 could be obtained via a multistep synthesis starting from diol 7. Several different methods were attempted to oxidize the unprotected diol to the alpha-hydroxy aldehyde. Finally, a route was chosen which involves a p rotection-deprotection sequence followed by oxidation of the free primary a lcohol. The resulting modified nucleosides should facilitate the study of C -3'-DNA radicals.