Towards novel amide-modified oligonucleotides: asymmetric synthesis of 5′-(S)-methyl-3′-carboxymethylene-3′-deoxythymidine

The synthesis of novel 5′-(S)-methyl-3′-carboxymethylene-3′-deoxythymidine is reported. Key steps involve diastereoselective lactonization, enantioselective enzymatic ester hydrolysis and diastereoselective glycosidation of a key intermediate with thymine with 100% β-selectivity via Lewis acid mediated cleavage of a [3.2.1] oxabicyclic lactone.