Abstract: This invention relates to a process for preparing an oligonucleotide 5?-triphosphate.

Abstract: 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.

Abstract: A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large-scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3?-protected compound of formula: with a nucleotide derivative having a 5?-protection group, or reacting a 5?-protected compound of formula with a nucleotide derivative having a 3?-protection group.

Abstract: The present invention describes simple, efficient, and enzyme-free method of making oligonucleotides with 5?-triphosphate. This invention presents novel process for synthesizing triphosphate oligonucleotides using a diaryl phosphonate as reagent. The process of the present invention is amenable to large-scale, economic 5?-triphosphate oligonucleotide synthesis.

Abstract: 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.

Abstract: A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large- scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3?-protected compound of formula: with a nucleotide derivative having a 5?-protection group, or reacting a 5?-protected compound of formula with a nucleotide derivative having a 3?-protection group.

Abstract: A solution phase synthesis method for preparing an oligonucleotide, wherein at least some of the reagents are solid supported. The method suitable for large-scale synthesis comprises coupling a protected compound with a nucleotide derivative having a protection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond; optionally processing the elongated oligonucleotide by capping by reaction with a solid supported capping agent and/or by oxidizing or sulfurizing by reaction of the oligonucleotide with a solid supported oxidizing or sulfurization reagent; and removing the protection group. The coupling may include reacting a 3?-protected compound of formula: with a nucleotide derivative having a 5?-protection group, or reacting a 5?-protected compound of formula with a nucleotide derivative having a 3?-protection group.

Abstract: A method for preparing an oligonucleotide comprising the steps of a) providing a 3-protected compound having the formula: wherein B is a heterocyclic base R2 is H, a protected 2-hydroxyl group, F, a protected amino group, an O-alkyl group, an O-substituted alkyl, a substituted alkylamino or a C4?-O2?methylen linkage R3 is OR?3, NHR?3, NR?3R??3, a 3?-protected nucleotide or a 3?-protected oligonucleotide, R?3 is a hydroxyl protecting group, R?3, R??3 are independently an amine protecting group, b) reacting said compound with a nucleotide derivative having a 5-proctection group in the presence of a solid supported activator to give an elongated oligonucleotide with a P(III)-internucleotide bond c) optionally processing the elongated oligonucleotide with a P(III)-internucleotide bond by either or both of steps c1) and c2) in any sequence c1) capping preferably by reacting with a solid supported capping agent c2) oxidizing preferably by reacting the oligonucleotide with a solid supported oxidizing reagent d) remo

Abstract: Therapeutic oligonucleotide analogues which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligomers with four atom linking groups forms unique di- and poly-nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

Abstract: Therapeutic oligonucleotide analogues which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligomers with four atom linking groups forms unique di- and poly-nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

Abstract: Therapeutic oligonucleotide analogues which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligomers with four atom linking groups forms unique di- and poly-nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.

Abstract: Therapeutic oligonucleotide analogues which have improved nuclease resistance and improved cellular uptake are provided. Replacement of the normal phosphorodiester inter-sugar linkages found in natural oligomers with four atom linking groups forms unique di- and poly- nucleosides and nucleotides useful in regulating RNA expression and in therapeutics. Methods of synthesis and use are also disclosed.