Thioether substituted aryl carbonate protecting groups

• US 8,097,711 B2
• Filed: 08/31/2007
• Issued: 01/17/2012
• Est. Priority Date: 09/02/2006
• Status: Active Grant

• Current Assignee: Agilent Technologies, Inc., The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: Agilent Technologies, Inc.
• Inventors: Timar, Zoltan, Kupihar, Zoltan, Dellinger, Douglas J., Caruthers, Marvin H.
• Primary Examiner(s): OLSON, ERIC
• Application Number:
  US11/897,898
• Publication Number:
  US 20080146787A1
• Time in Patent Office: 1,600 Days
• Field of Search: None
• US Class Current: 536/23.1
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C07H 21/02 with ribosyl as saccharide radical
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Embodiments of the invention include nucleotide and nucleoside monomers protected at the 5′- or 3′-hydroxyls with thioether substituted aryl carbonate protecting groups. In certain cases, the carbonate protecting groups include an aryl moiety, e.g., a phenyl group, attached to the carbonate, where the aryl moiety further includes a thioether group, e.g., an alkyl or aryl thioether group, bound directly to the aryl ring. Aspects of the invention further include methods of synthesizing nucleic acids, e.g., oligonucleotides, using such protected nucleoside monomer monomers, as well as nucleic acids produced using methods of the invention and compositions thereof.

Claims

1. A compound having one of the following structures:

2. The compound according to claim 1, wherein R1 has the structure:

3. A method comprising:

(a) contacting a first nucleoside moiety comprising a free hydroxyl group with a compound having one of the following structures;

4. The method according to claim 3, wherein said first nucleoside moiety is covalently bonded to a solid support.

5. The method according to claim 3, wherein R1 has the structure:

6. The method according to claim 3, wherein said polynucleotide is bonded to a solid support.

7. The method according to claim 6, wherein said method further comprises separating said polynucleotide from said solid support to produce a free polynucleotide.

8. The method according to claim 7, wherein said method further comprises combining said free polynucleotide with a pharmaceutically acceptable carrier to form a pharmaceutically acceptable composition.

9. The method according to claim 7, wherein said method further comprises chemically modifying said free polynucleotide to produce a modified free polynucleotide.

10. The method according to claim 9, wherein said method further comprises combining said modified free polynucleotide with a pharmaceutically acceptable composition.

11. The method according to claim 3, wherein said polynucleotide is a DNA.

12. The method according to claim 3, wherein said polynucleotide is a RNA.