The present invention discloses novel methods for the synthesis of
oligonucleotides and nucleoside phosphoramidites. The methods are based
on employing aryl-substituted 5-phenyl-1H-tetrazoles with perfluoroalkyl
groups on the aromatic ring as activators. In one aspect the novel
activators are used in the synthesis of oligonucleotides via the
phosphoramidite approach. In this aspect the activators are highly
efficient and can be applied with very short coupling times. In a further
aspect, the activators of the invention are used in the synthesis of
phosphoramidites through the reaction of nucleosides comprising a free
hydroxyl group with phosphitylating agents. In this aspect the activators
provide very pure phosphoramidites under mild conditions. The activators
of the invention are further characterized by being highly soluble,
non-hygroscopic and non-hazardous.