THIOCARBON-PROTECTING GROUPS FOR RNA SYNTHESIS

• US 20120238737A1
• Filed: 05/31/2012
• Published: 09/20/2012
• Est. Priority Date: 05/10/2007
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc.
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Dellinger, Douglas J., Sierzchala, Agnieszka, Turner, John, Myerson, Joel, Caruthers, Marvin H., Dellinger, Geraldine F., Kupihar, Zoltan, Ferreira, Fernando
• Granted Patent: US 9,067,961 B2
• Time in Patent Office: Days
• US Class Current: 536/23.1
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 13/12 by acids having the group -X-C(=X)-X-, or halides thereof, in which each X means nitrogen, oxygen, sulfur, selenium or tellurium, e.g. carbonic acid, carbamic acid
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 21/02 with ribosyl as saccharide radical
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Aspects of the invention include 2′ protected nucleoside monomers that are protected at the 2′ site with thiocarbon protecting groups. Thiocarbon protecting groups of interest include thiocarbonate, thionocarbonate, dithiocarbonate groups, as well as thionocarbamate protecting groups. Aspects of the invention further include nucleic acids that include the protecting groups of the invention, as well as methods of synthesizing nucleic acids using the protecting groups of the invention.

Claims

1. A compound having the structure of formula (II):

2. The compound according to claim 1, wherein W is —

NH—

R⁴, and the compound has the structure of formula (IIe);

3. The compound according to claim 1, wherein W is —

NR⁴—

R⁵, and the compound has the structure of formula (IIf);

4. The compound according to claim 1, wherein W is —

NH—

O—

R⁴, and the compound has the structure of formula (IIg);

5. The compound according to claim 1, wherein W is —

NR⁴—

O—

R⁵, and the compound has the structure of formula (IIh);

6. The compound according to claim 1, wherein the compound is one of:

7. The compound according to claim 1, wherein the compound is:

8. The compound according to claim 1, wherein

B^P is a protected or unprotected heterocyclic base;

one of R¹ and R² is a protecting group, and the other of R¹ and R² is a phosphoramidite group.

9. A method comprising:

(a) providing a nucleoside residue, wherein said nucleoside residue comprises an unprotected hydroxyl group and a 2′

-protected nucleotide monomer, wherein said 2′

-protected nucleotide monomer has the structure of formula (II);

10. The method according to claim 9, wherein said method further comprises exposing said internucleotide bond to an oxidizing agent.

11. The method according to claim 10, wherein said method further comprises reiterating said contacting step at least once.

12. The method according to claim 9, wherein said method further comprises removing said 2′

-hydroxyl protecting group.

13. The method according to claim 9, wherein said nucleoside residue is covalently bound to a solid support.

14. The method according to claim 13, wherein said method further comprises cleaving said nucleic acid from said solid support to produce a free nucleic acid.

15. The method according to claim 9, wherein said 2′

-protected nucleotide monomer has the structure of formula (IIe) or formula (IIf);

16. The method according to claim 9, wherein said 2′

-protected nucleotide monomer has the structure of formula (IIg) or formula (IIh);

17. The method according to claim 9, wherein said 2′

-protected nucleotide monomer is one of;

18. The method according to claim 9, wherein said 2′

-protected nucleotide monomer is;

19. The method according to claim 9, further comprising:

(c) oxidizing said internucleotide bond to produce a nucleic acid;

(d) cleaving said nucleic acid from said solid support to produce a free nucleic acid; and

(e) chemically modifying said free nucleic acid to produce a modified nucleic acid.

20. A 2′

-O-protected nucleic acid comprising the structure;

21. The 2′

-O-protected nucleic acid of claim 20, wherein Q is