Novel protective group for synthesis of RNA and derivative

• US 20110178284A1
• Filed: 09/15/2010
• Published: 07/21/2011
• Est. Priority Date: 09/16/2009
• Status: Active Grant

• Current Assignee: WAVE Life Sciences Ltd.
• Original Assignee: Chiralgen, Ltd.
• Inventors: SHIMIZU, Mamoru, WADA, Takeshi
• Granted Patent: US 8,470,987 B2
• Time in Patent Office: Days
• US Class Current: 536/25.3
• CPC Class Codes: C07F 9/65586 at least one of the hetero rings does not contain nitrogen as ring hetero atom
• CPC Class Codes: C07F 9/65616 containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
• CPC Class Codes: C07F 9/65844 the phosphorus atom being part of a five-membered ring which may be condensed with another ring system
• CPC Class Codes: C07H 19/067 with ribosyl as the saccharide radical
• CPC Class Codes: C07H 19/167 with ribosyl as the saccharide radical
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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 C_1-6 alkyl group, or a C_1-6 halo-substituted alkyl group; R³ and R⁴ represent hydrogen atom, a halogen atom, a C_1-6 alkyl group, or a C_1-6 halo-substituted alkyl group; and R⁵ and R⁶ represent a halogen atom, a C_1-6 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.

Claims

1. A protective group for 2′

-hydroxyl group of a ribonucleoside, a ribonucleotide, or a derivative thereof, which is represented by the following general formula (I);

2. The protective group according to claim 1, wherein both R¹ and R² are hydrogen atoms.

3. The protective group according to claim 1, wherein both R³ and R⁴ are hydrogen atoms.

4. The protective group according to claim 1, wherein R⁵ and R⁶ independently represent a halogen atom or a fluoro-substituted C_1-6 alkyl group.

5. The protective group according to claim 1, wherein R⁵ and R⁶ represent the same fluoro-substituted C_1-6 alkyl group.

6. The protective group according to claim 1, wherein R⁵ and R⁶ represent the same perfluoro(C_1-6 alkyl) group.

7. The protective group according to claim 1, wherein both R⁵ and R⁶ are trifluoromethyl groups.

8. The protective group according to claim 1, wherein the derivative of ribonucleotide is a phosphoroamidite compound.

9. A ribonucleoside, a ribonucleotide, or a derivative thereof, wherein oxygen atom of 2′

-hydroxyl group is protected with the protective group according to claim 1.

10. The derivative of ribonucleotide according to claim 9, which is a phosphoroamidite compound.

11. The derivative of ribonucleotide according to claim 10, wherein the phosphoroamidite compound is a compound represented by the following general formula (II):

12. The derivative of ribonucleotide according to claim 11 which is a compound represented by the following formula (IIA):

13. A method for preparing an oligoribonucleic acid, which uses the phosphoroamidite compound according to claim 11.

14. A reagent for protecting 2′

-hydroxyl group of a ribonucleoside, a ribonucleotide, or a derivative thereof, which comprises a compound represented by the following general formula (III);

15. A method for introducing a protective group for 2′

-hydroxyl group of a ribonucleoside, a ribonucleotide, or a derivative thereof, which is represented by the following general formula (I);

16. A method for introducing the protective group for 2′

-hydroxyl group of a ribonucleoside, a ribonucleotide, or a derivative thereof, which is represented by the following general formula (I);