Chemical rna synthesis method

C - Chemistry – Metallurgy – 07 – H

Patent

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Details

C07H 1/00 (2006.01) C07H 19/06 (2006.01) C07H 19/16 (2006.01) C07H 21/02 (2006.01)

Patent

CA 2726260

The invention relates to a method for the chemical synthesis of RNA, comprising the following steps: a) bonding to a solid support of a monomer having formula (II) in which - X1 is a dimethoxytrityl group, - X6 is H or an OAc group or OX3,in which X3 is a group having formula (A), in which X is O or S, R' is H or CH3 and R is selected from a linear or branched alkyl group at C1 to C4 and a R1-O-R2 group in which R1 is an alkyl group at C1 to C2 and R2 is a CH3 group or CH2CH2-O-CH3 or aryl; b) assembly with the monomer having formula (II) bound to the support thereof obtained in step (a) of at least one monomer having formula (III) in which X1, Bp, X3 are as defined for formula (II) and X5 is a hydrogen phosphonate monoester or phosphoramidite group, preferably a 2-cyanoethyl-N, N-diisopropylphosphoramidite group, which is used to obtain a protected single-strand RNA bound to a support.

L'invention propose un procédé de synthèse d'ARN par voie chimique comprenant les étapes de : a) liaison à un support solide d'un monomère de formule (II) suivant dans laquelle: - X1 est un groupe diméthoxytrityle, - X6 est H ou un groupe OAc ou OX3 dans lequel X3 est un groupe de formule (A) suivante : dans laquelle X est O ou S, R' est H ou CH3 et R est choisi parmi un groupe alkyle en C1 à C4 linéaire ou ramifié et un groupe R1-O-R2 dans lequel R1 est un groupe en C1 à C2 et R2 est un groupe CH3 ou CH2CH2-O-CH3 ou aryle b) assemblage, avec le monomère de formule (II) lié à son supporr obtenu à l'étape a), d'au moins un monomère de formule (III) suivante : dans laquelle X1, Bp, X3 sont tels que definis pour la formule (I1) et X5 est un groupe hydrogènophosphonate monoester ou phosphoramidite, de préférence un groupe 2-cyanoéthyl-N, N-diisopropylphosphoramidite, ce par quoi on obtient un ARM simple brin protégé lié a un support.

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