Reagents that facilitate the purification of compounds synthesized on a solid support

• US 20030232978A1
• Filed: 08/15/2002
• Published: 12/18/2003
• Est. Priority Date: 08/24/2001
• Status: Abandoned Application

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Palmacci, Emma R., Plante, Obdiah J., Seeberger, Peter H., Hewitt, Michael C.
• Application Number:
  US10/219,129
• Publication Number:
  US 20030232978A1
• Time in Patent Office: Days
• US Class Current: 536/25.3
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07B 63/02 by treatment giving rise to a chemical modification
• 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 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C40B 40/12 Libraries containing saccharides or polysaccharides, or derivatives thereof
• CPC Class Codes: C40B 50/14 Solid phase synthesis, i.e. wherein one or more library building blocks are bound to a solid support during library creation; Particular methods of cleavage from the solid support
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes
• CPC Class Codes: C40B 99/00 Subject matter not provided for in other groups of this subclass

Abstract

Disclosed is a novel capping-and-tagging (“cap-tag”) strategy that aids in the purification of compounds assembled by multi-step synthetic methods. The incorporation of a unique cap-tag into undesired intermediates during a multi-step synthesis allows for the straightforward removal of these undesired compounds at the conclusion of the synthetic protocol by several methods based on affinity chromatography and scavenging resins. Importantly, this invention may be exploited in any automated synthetic protocol. In preferred embodiments, the cap-tag system is exploited for the purification of carbohydrates prepared via automated solid-phase methods.

Claims

1. A method of facilitating the purification of compounds synthesized on a solid support, comprising the step of:

treating a compound covalently tethered to a solid support, wherein said compound comprises a nucleophilic functional group, with a capping-tagging reagent selected from the group consisting of activated azido-carboxylic acids, azido-carboxylic acid anhydrides, fluoroalkylsilyl sulfonates, and fluoroalkylsilyl halides, thereby forming a second compound tethered to a solid support.

2. The method of claim 1, wherein the compound covalently tethered to a solid support is a biopolymer.

3. The method of claim 1, wherein the compound covalently tethered to a solid support is an oligosaccharide.

4. The method of claim 1, wherein the compound covalently tethered to a solid support is an oligonucleotide.

5. The method of claim 1, wherein the nucleophilic functional group is an alcohol.

6. The method of claim 1, wherein the nucleophilic functional group is an amine.

7. The method of claim 1, wherein the capping-tagging reagent is an activated 2-azido-carboxylic acid or 2-azido-carboxylic acid anhydride.

8. The method of claim 1, wherein the capping-tagging reagent is a 2-azido-carboxylic acid anhydride.

9. The method of claim 1, wherein the capping-tagging reagent is 2-azido-isobutyric acid anhydride.

10. The method of claim 1, wherein the capping-tagging reagent is a fluoroalkylsilyl triflate.

11. The method of claim 1, wherein the capping-tagging reagent is a fluoroalkyldiisopropylsilyl triflate.

12. The method of claim 1, wherein the capping-tagging reagent is heptadecafluorodecyldiisopropylsilyl triflate.

13. The method of claim 1, wherein the compound covalently tethered to a solid support is an oligosaccharide;

and the nucleophilic functional group is an alcohol.

14. The method of claim 1, wherein the compound covalently tethered to a solid support is an oligonucleotide;

and the nucleophilic functional group is an alcohol.

15. The method of claim 1, wherein the compound covalently tethered to a solid support is an oligosaccharide;

the nucleophilic functional group is an alcohol; and

the capping-tagging reagent is 2-azido-isobutyric acid anhydride.

16. The method of claim 1, wherein the compound covalently tethered to a solid support is an oligonucleotide;

the nucleophilic functional group is an alcohol; and

the capping-tagging reagent is 2-azido-isobutyric acid anhydride.

17. The method of claim 1, wherein the compound covalently tethered to a solid support is an oligosaccharide;

the nucleophilic functional group is an alcohol; and

the capping-tagging reagent is heptadecafluorodecyldiisopropylsilyl triflate.

18. The method of claim 1, wherein the compound covalently tethered to a solid support is an oligonucleotide;

the nucleophilic functional group is an alcohol; and

the capping-tagging reagent is heptadecafluorodecyldiisopropylsilyl triflate.

19. The method of any of claims 1-18, further comprising the steps of:

cleaving said tether of said second compound covalently tethered to a solid support to produce a compound in solution; and

purifying said compound in solution using affinity chromatography or a scavenging resin.

20. The method of claim 19, wherein said compound in solution is purified using affinity chromatography with a fluorous silica gel as a stationary phase.

21. The method of claim 19, wherein said compound in solution is purified using a scavenging resin comprising an isocyanate, isothiocyanate, alkyl halide, aryl halide, aryl boronic acid, alkyl sulfonate, aldehyde, carboxylic acid halide, carboxylic acid anhydride, or sulfonyl halide.

22. The method of claim 19, wherein said compound in solution is purified using a scavenging resin comprising an isocyanate or isothiocyanate.