Facile amide formation via S-nitroso thioacid intermediates
Provided are methods for forming a reactive S-nitroso thioacid (NTA), comprising nitrosation of a thioacid with a nitrosation reagent. Also provided are methods for: acylating a nucleophile including selective acylation with a high degree of selectivity toward amines over hydroxyls; amide or peptide bond formation; forming a dipeptide or polypeptide; and peptide coupling/ligation, comprising use of thioacid and amine starting materials, wherein the reactions are mediated by very reactive S-nitroso thioacid (NTA) intermediates enabling extremely fast reactions under mild conditions, providing for broad applications.
1. A method for forming a reactive S-nitroso thioacid (NTA), comprising nitrosation of a thioacid with a nitrosation reagent in solution to form a reactive S-nitroso thioacid (NTA) intermediate wherein the thio moiety of the thioacid is nitrosated by the nitrosation reagent, wherein the thioacid is selected from a compound having formula I:
wherein R 1 is selected from any moiety or group.
2. The method of claim 1 , wherein the solution comprises an aqueous solution.
3. The method of claim 1 , wherein the solution comprises an aqueous-organic mixture.
4. The method of claim 1 , wherein the solution comprises an organic solution.
5. The method of claim 1 , wherein the nitrosation reagent comprises at least one reagent selected from the group consisting of an organonitrite (RONO), HCl/NaNO 2 , and a nitrosonium salt.
6. The method of claim 5 , wherein the organonitrite comprises amyl nitrite.
7. A method for acylating a nucleophile, comprising: nitrosation of a thioacid with a nitrosation reagent in solution to form a reactive S-nitroso thioacid (NTA) intermediate wherein the thio moiety of the thioacid is nitrosated by the nitrosation reagent; and contacting the NTA intermediate with a nucleophile to provide for acylation of the nucleophile, wherein the thioacid is selected from a compound having formula I:
wherein R 1 is selected from any moiety or group.
8. The method of claim 7 , wherein the nucleophile is selected from a primary or secondary amine.
9. The method of claim 7 , wherein the solution comprises an aqueous solution.
10. The method of claim 7 , wherein the solution comprises an aqueous-organic mixture.
11. The method of claim 7 , wherein the solution comprises an organic solution.
12. The method of claim 7 , wherein the nitrosation reagent comprises at least one reagent selected from the group consisting of an organonitrite (RONO), HCl/NaNO 2 , and a nitrosonium salt.
13. The method of claim 12 , wherein the organonitrite comprises amyl nitrite.
14. A method for forming an amide bond, comprising: nitrosation of a thioacid with nitrosation reagent in solution to form a reactive S-nitroso thioacid (NTA) intermediate wherein the thio moiety of the thioacid is nitrosated by the nitrosation reagent; and contacting the NTA intermediate with an amine to provide for forming an amide bond, wherein the thioacid is selected from a compound having formula I:
wherein R 1 is selected from any moiety or group.
15. The method of claim 14 , wherein the solution comprises an aqueous solution.
16. The method of claim 14 , wherein the solution comprises an aqueous-organic mixture.
17. The method of claim 14 , wherein the solution comprises an organic solution.
18. The method of claim 14 , wherein the amine is selected from a primary and/or secondary amine.
19. The method of claim 14 , wherein the nitrosation reagent comprises at least one reagent selected from the group consisting of an organonitrite (RONO), HCl/NaNO 2 , and a nitrosonium salt.
20. The method of claim 19 , wherein the organonitrite comprises amyl nitrite.
21. The method of claim 14 , wherein contacting the NTA intermediate with an amine to provide for forming an amide bond comprises forming a dipeptide or polypeptide.
22. The method of claim 21 , wherein the solution comprises an aqueous solution.
23. The method of claim 21 , wherein the solution comprises an aqueous-organic mixture.
24. The method of claim 21 , wherein the solution comprises an organic solution.
25. The method of claim 17 , wherein the amine is selected from a primary and/or secondary amine.
26. The method of claim 17 , wherein the nitrosation reagent comprises at least one reagent selected from the group consisting of an organonitrite (RONO), HCl/NaNO 2 , and a nitrosonium salt.
27. The method of claim 26 , wherein the organonitrite comprises amyl nitrite.
28. The method of claim 21 , further comprising nitrosation of a thioacid derivative of the dipeptide or the polypeptide with a nitrosation reagent in solution to form a reactive S-nitroso thioacid (NTA) intermediate; and contacting the NTA intermediate with an amine group of a second polypeptide to provide for forming a larger, ligated polypeptide.
29. The method of claim 23 , wherein the first and the second polypeptides comprise contiguous amino acid subregions of a desired larger polypeptide.
30. The method of claim 28 , wherein the nitrosation reagent comprises at least one reagent selected from the group consisting of an organonitrite (RONO), HCl/NaNO 2 , and a nitrosonium salt.
31. The method of claim 30 , wherein the organonitrite comprises amyl nitrite.