Protective group for synthesis of RNA and derivative
AssigneeChiralgen, Ltd.
InventorsTakeshi Wada, Mamoru Shimizu
Life of this patent
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Abstract
A protective group represented by the following general formula (I) (the oxygen atom attached with * represents oxygen atom of 2′-hydroxyl group of a ribonucleoside, a ribonucleotide or a derivative thereof; R1 and R2 both represent hydrogen atom, or represent a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group; R3 and R4 represent hydrogen atom, a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group; and R5 and R6 represent a halogen atom, a C1-6 halo-substituted alkyl group, cyano group, nitro group, or the like), which is stable under the reaction conditions of the nucleic acid synthetic cycles and has little steric hindrance, and can be removed under mild conditions using fluoride ions as a base.
Claims14
A protective group for 2′-hydroxyl group of a ribonucleoside or ribonucleotide, which is represented by the following general formula (I):
- wherein, the oxygen atom attached with * represents an oxygen atom of the 2′-hydroxyl group of a ribonucleoside or ribonucleotide;
- R1 and R2 both represent a hydrogen atom, or independently represent a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group;
- R3 and R4 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group;
- and R5 and R6 represent the same fluoro-substituted C1-6 alkyl group or the same perfluoro(C1-6 alkyl) group.
A method for introducing a protective group for a 2′-hydroxyl group of a ribonucleoside or ribonucleotide, which is represented by the following general formula (I):
- wherein, the oxygen atom attached with * represents an oxygen atom of the 2′-hydroxyl group of a ribonucleoside or ribonucleotide;
- R1 and R2 both represent a hydrogen atom, or independently represent a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group;
- R3 and R4 independently represent a hydrogen atom, a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group;
- and R5 and R6 represent the same fluoro-substituted C1-6 alkyl group or the same perfluoro(C1-6 alkyl) group, wherein the method comprises reacting a reagent comprising a compound represented by the following general formula (III):
- wherein, R3, R4, R5, and R6 have the same meanings as those defined above, and R21 represents a hydroxyl group, with a ribonucleoside or a ribonucleotide of which the 2′-hydroxyl group is protected with a C1-6 alkylthiomethyl group.
A method for introducing the protective group for a 2′-hydroxyl group of a ribonucleoside or a ribonucleotide, which is represented by the following general formula (I):
- wherein, the oxygen atom attached with * represents oxygen atom of 2′-hydroxyl group of a ribonucleoside, a ribonucleotide or a derivative thereof;
- R1 and R2 both represent hydrogen atom, or independently represent a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group;
- R3 and R4 independently represent hydrogen atom, a halogen atom, a C1-6 alkyl group, or a C1-6 halo-substituted alkyl group;
- and R5 and R6 represent the same fluoro-substituted C1-6 alkyl group or the same perfluoro(C1-6 alkyl) group,
- wherein the method comprises reacting a reagent comprising a compound represented by the following general formula (III):
- wherein, R3, R4, R5, and R6 have the same meanings as those defined above, R21 represents R22—S—C(R1)(R2)—O—, wherein in the formula R22 represents a C1-6 alkyl group, and R1 and R2 have the same meanings as those defined above, or X—C(R1)(R2)—O—, wherein in the formula, X represents a leaving group, and R1 and R2 have the same meanings as those defined above, with a ribonucleoside or ribonucleotide of which the 2′-hydroxyl group is not protected.
Dependencies are inferred from the claim text.