Solution phase synthesis of oligonucleotides

C - Chemistry – Metallurgy – 07 – H

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C07H 21/00 (2006.01) C07D 207/48 (2006.01) C07D 265/33 (2006.01) C07F 9/165 (2006.01) C07F 9/18 (2006.01) C07H 19/10 (2006.01) C07H 19/20 (2006.01)

Patent

CA 2300874

A process for the synthesis in solution phase of a phosphorothioate triester is provided. The process comprises the solution phase coupling of an H- phosphonate with an alcohol in the presence of a coupling agent to form an H- phosphonate diester. The H-phosphonate diester is oxidised in situ with a sulfur transfer agent to produce the phosphorothioate triester. Preferably, the H-phosphonate and alcohol are protected nucleosides or oligonucleotides. Oligonucleotide H-phosphonates which can be used in the formation of phosphorothioate triesters are also provided.

Procédé servant à effectuer la synthèse dans une phase de solution d'un triester de phosphorothioate. Ce procédé consiste à coupler la phase de solution d'un H-phosphonate avec un alcool en présence d'un agent de couplage afin d'obtenir un diester de H-phosphonate. On oxyde ce diester de H-phosphonate in situ par un agent de transfert de soufre, de manière à obtenir le triester de phosphorothioate. Le H-phosphonate et l'alcool sont, de préférence, des nucléosides ou des oligonucléotides protégés. L'invention concerne également des H-phosphonates d'oligonucléotides qu'on peut utiliser afin de produire des triesters de phosphorothioate.

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