A novel phosphate protection for oligonucleotide synthesis: the 2-[(1-naphthyl)carbamoyloxy]ethyl (NCE) group

The utility of the 2-(arylcarbamoyloxy)ethyl group for protection of internucleosidic phosphate linkages in oligonucleotide synthesis was studied. Of the three protecting groups tested, the 2-[(1-naphthyl)carbamoyloxy]ethyl demonstrated high coupling yields, favorable deprotection kinetics and the highest hydrolytic stability of the thymidine phosphoramidite building block. The mechanism of deprotection was confirmed by deprotecting a model phosphate triester and synthetic dodecathymidylate.