Alkynes and methods of reacting alkynes with 1,3-dipole-functional compounds

Patent metadata

Field	Value
Publication number	US-9932297-B2
Application number	US-201715657601-A
Country	US
Kind code	B2
Filing date	Jul 24, 2017
Priority date	Nov 21, 2007
Publication date	Apr 3, 2018
Grant date	Apr 3, 2018

Abstract

1,3-Dipole-functional compounds (e.g., azide functional compounds) can be reacted with certain alkynes in a cyclization reaction to form heterocyclic compounds. Useful alkynes (e.g., strained, cyclic alkynes) and methods of making such alkynes are also disclosed. The reaction of 1,3-dipole-functional compounds with alkynes can be used for a wide variety of applications including the immobilization of biomolecules on a substrate.

First claim

What is claimed is:

1. A compound of the formula:

wherein:
each R 1 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
each R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
X represents C═O, C═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ;
each R 3 and R 4 independently represents hydrogen or an organic group; and
R 8 represents an organic group.

2. The compound of claim 1 wherein R 8 represents a biomolecule.

3. The compound of claim 2 wherein the biomolecule is selected from the group consisting of peptides, proteins, glycoproteins, nucleic acids, lipids, saccharides, oligosaccharides, polysaccharides, and combinations thereof.

4. A compound of the formula:

wherein:
each R 1 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
each R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
X represents C═O, C═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ; and
each R 3 , R 4 , and R 10 independently represents hydrogen or an organic group, with the proviso that at least one R 10 represents an organic group.

5. The compound of claim 4 wherein the at least one R 10 representing an organic group represents a biomolecule.

6. The compound of claim 5 wherein the biomolecule is selected from the group consisting of peptides, proteins, glycoproteins, nucleic acids, lipids, saccharides, oligosaccharides, polysaccharides, and combinations thereof.

7. A method of preparing the compound of claim 1 , the method comprising:
combining at least one alkyne with at least one 1,3-dipole-functional compound, comprising a nitrile oxide-functional compound; and
allowing the at least one 1,3-dipole-functional compound and the at least one alkyne to react under conditions effective to form the heterocyclic compound;
wherein the alkyne is of the formula:

wherein:
each R 1 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
each R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
X represents C═O, C═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ; and
each R 3 and R 4 independently represents hydrogen or an organic group.

8. The method of claim 7 wherein conditions effective to form the heterocyclic compound comprise the substantial absence of added catalyst.

9. The method of claim 7 wherein the at least one 1,3-dipole-functional compound comprises a 1,3-dipole-functionalized biomolecule.

10. The method of claim 7 wherein the at least one 1,3-dipole-functional compound comprises a detectable label.

11. The method of claim 10 further comprising detecting the heterocyclic compound.

12. The method of claim 10 wherein the detectable label is an affinity label.

13. The method of claim 12 further comprising isolating the heterocyclic compound using affinity binding.

14. A method of preparing the compound of claim 4 , the method comprising:
combining at least one alkyne with at least one 1,3-dipole-functional compound comprising a nitrone-functional compound; and
allowing the at least one 1,3-dipole-functional compound and the at least one alkyne to react under conditions effective to form the heterocyclic compound;
wherein the alkyne is of the formula:

wherein:
each R 1 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
each R 2 is independently selected from the group consisting of hydrogen, halogen, hydroxy, alkoxy, nitrate, nitrite, sulfate, and a C1-C10 organic group;
X represents C═O, C═N—OR 3 , C═N—NR 3 R 4 , CHOR 3 , or CHNHR 3 ; and
each R 3 and R 4 independently represents hydrogen or an organic group.

15. The method of claim 14 wherein conditions effective to form the heterocyclic compound comprise the substantial absence of added catalyst.

16. The method of claim 14 wherein the at least one 1,3-dipole-functional compound comprises a 1,3-dipole-functionalized biomolecule.

17. The method of claim 14 wherein the at least one 1,3-dipole-functional compound comprises a detectable label.

18. The method of claim 17 further comprising detecting the heterocyclic compound.

19. The method of claim 17 wherein the detectable label is an affinity label.

20. The method of claim 19 further comprising isolating the heterocyclic compound using affinity binding.

Assignees

• Univ Georgia

Inventors

• Boons Geert-Jan
• Guo Jun
• Ning Xinghai
• Wolfert Margaretha

Classifications

• A61P37/04

  Immunostimulants · CPC title

• C07C35/37 Primary

  with a hydroxy group on a condensed system having three rings · CPC title

• A61K49/0021 Primary

  the fluorescent group being a small organic molecule · CPC title

• A61K49/0052

  Small organic molecules (oligomers, polymers, dendrimers A61K49/0054) · CPC title

• A61K49/0043

  Fluorescein, used in vivo · CPC title