SYNTHESIS OF NOVEL 3'-C-(HYDROXYMETHYL)THYMIDINES AND OLIGODEOXYNUCLEOTIDE ANALOGS CONTAINING COMPRESSED 3'-C-HYDROXYMETHYL-LINKED PHOSPHODIESTER BACKBONES

Lombardo methylenation of the novel 2'-deoxy-3'-ketonucleosides 4 affo rded 2',3'-dideoxy-3'-C-methylene nucleosides 5, which were subjected to catalytic dihydroxylation reactions. In the case of 5'-deoxynucleos ide 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 5a and 7a as a 10:3 mixture. 5'-O-Silylated nucleoside 6b was converted into the phosphoramidite synthon 9, which was applied in automated synthes es of oligodeoxynucleotides containing novel compressed 3'-C-hydroxyme thyl-linked phosphodiester backbones.