Multiple phosphate-linked nucleotide couplings via 5′ silyl ether protection in the phosphite triester and phosphoramidite approaches

Phosphite triester and phosphoramidite coupling methodologies are described for performing fourfold solution phase installations of standard deoxynucleotides onto a single cavitand template molecule. The methodologies here are based on 5′ silyl ether protection of the appropriate nucleoside or nucleoside phosphoramidite. Synthesis of a novel water-soluble species incorporating four covalently-linked guanine nucleotides is shown.