Activators for oligonucleotide synthesis

C - Chemistry – Metallurgy – 07 – H

Patent

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C07H 21/00 (2006.01)

Patent

CA 2330192

The present invention relates to improved methods for the preparation of nucleoside phosphoramidites and oligonucleotides. In one aspect, the methods of the invention are used to prepare phosphitylating reagents using pyridinium salts as activators. In a further aspect, the methods of the invention are used to prepare internucleoside linkages using activators which include at least one pyridinium salt and at least one substituted imidazole. In a further aspect, methods are provided for the preparation of internucleoside linkages between nucleosides having 2'-substituents using imidazolium or benzimidazolium salts as an activator. In a further aspect, methods are provided for the preparation of internucleoside linkages between nucleosides having bioreversible protecting group that confers enhanced chemical and biophysical properties, without exocyclic amine protection, using imidazolium or benzimidazolium salts as an activator.

L'invention concerne des procédés améliorés permettant d'élaborer des oligonucléotides et des phosphoramidites de nucléoside. Selon un aspect, les procédés considérés permettent d'élaborer des réactifs de phosphitylation en utilisant des sels de pyridinium comme activateurs. Selon un deuxième aspect, les procédés décrits permettent d'établir des liaisons internucléoside en utilisant des activateurs qui comportent au moins un sel de pyridinium et au moins un imidazole substitué. Selon un troisième aspect, on décrit des procédés qui permettent d'établir des liaisons internucléoside entre nucléosides à substituants en 2', en utilisant comme activateurs des sels d'imidazolium ou de benzimidazolium. Selon un quatrième aspect, les procédés présentés permettent d'établir des liaisons internucléoside entre nucléosides à groupe de protection bioréversible qui confère des propriétés chimiques et biophysiques améliorées, sans protection amine exocyclique, en utilisant comme activateurs des sels d'imidazolium ou de benzimidazolium.

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