Synthesis of novel 3'-C-(hydroxymethyl)thymidines and oligodeoxynucleotide analogues containing compressed 3'-C-hydroxymethyl-linked phosphodiester backbones

Article abstract of DOI:10.1080/15257779508009485

Lombardo methylenation of the novel 2'-deoxy-3'-ketonucleosides 4 afforded 2',3'-dideoxy-3'-C-methylene nucleosides 5, which were subjected to catalytic dihydroxylation reactions. In the case of 5'-deoxynucleoside 5a, a 1:1 mixture of 3'-C-hydroxymethyl diastereoisomers 6a and 7a was obtained, whereas the 5'-O-silylated nucleoside 5b afforded 3'-C- (hydroxymethyl)thymidine derivative 6b as the only product. Sharpless asymmetric dihydroxylation of 5a proceeded in low yield to give 6a and 7a as a 10:3 mixture. 5'-O-Silylated nucleoside 6b was converted into the phosphoramidite synthon 9, which was applied in automated syntheses of oligodeoxynucleotides containing novel compressed 3'-C-hydroxymethyl linked phosphodiester backbones.