ORGN 654

This paper reports the use of common peptide coupling reagents such as dicyclohexylcarbodiimide and HATU to effect the coupling of 5'-Fmoc protected H-phosphonate nucleotide monomers to a second nucleotide in the solution phase. Novel chemistry for the amine-selective acetylation of cytidine and 2'-deoxycytidine using electron-deficient benztriazole derivatives was also discovered and will be discussed.

This technique has the potential to be extended to solid-phase synthesis, utilising on-line UV monitoring of the dibenzofulvene adduct produced by deprotection of Fmoc with piperidine and offers significant opportunities in alternative approaches to oligonucleotide synthesis.