Reagent controlled stereoselective glycosylation
Provided are methods for the efficient stereoselective formation of glycosidic bonds, without recourse to prosthetic or directing groups.
1. A method of forming a glycosidic bond, comprising:
combining a first solvent, a reducing sugar, and a first strong Bronsted base, thereby forming a first reaction mixture;
combining a sulfonylating agent and the first reaction mixture, thereby forming a glycosyl sulfonate;
combining a second solvent, a glycosyl acceptor, and a second strong Bronsted base, thereby forming a second reaction mixture; and
combining the glycosyl sulfonate and the second reaction mixture, thereby forming a glycosidic bond;
wherein the reducing sugar is a pyranose; the sulfonylating agent is selected from the group consisting of tosyl 4-nitroimidazole, benzenesulfonyl 4-nitroimidazole, and p-toluenesulfonic anhydride; and the glycosidic bond is formed with greater than or equal to 90% stereoselectivity for a β linkage.
2. The method of claim 1 , wherein the glycosidic bond is formed with greater than or equal to 95% stereoselectivity for a β linkage.
3. The method of claim 1 , wherein the reducing sugar is a 2-deoxy sugar.
4. The method of claim 1 , wherein the reducing sugar is a D -sugar.
5. The method of claim 1 , wherein the reducing sugar is an L -sugar.
6. The method of claim 1 , wherein the first strong Bronsted base is non-nucleophilic.
7. The method of claim 1 , wherein the second strong Bronsted base is non-nucleophilic.
8. The method of claim 1 , wherein the first strong Bronsted base is non-nucleophilic; and the second strong Bronsted base is non-nucleophilic.
9. The method of claim 1 , wherein the first strong Bronsted base is selected from the group consisting of: alkali metal alkoxides, alkali metal amides, alkaline earth metal alkoxides, and alkaline earth metal amides.
10. The method of claim 1 , wherein the first strong Bronsted base is selected from the group consisting of: sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, lithium diisopropylamide, lithium tetramethylpiperidide, sodium hexamethyldisilazane (NaHMDS), and potassium hexamethyldisilazane (KHMDS).
11. The method of claim 1 , wherein the second strong Bronsted base is selected from the group consisting of: alkali metal alkoxides, alkali metal amides, alkaline earth metal alkoxides, and alkaline earth metal amides.
12. The method of claim 1 , wherein the second strong Bronsted base is selected from the group consisting of: sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, lithium diisopropylamide, lithium tetramethylpiperidide, sodium hexamethyldisilazane (NaHMDS), and potassium hexamethyldisilazane (KHMDS).
13. The method of claim 1 , wherein the first strong Bronsted base is same as the second strong Bronsted base.
14. The method of claim 1 , wherein the first reaction mixture further comprises tri-tert-butylpyrimidine (TTBP).
15. The method of claim 1 , wherein the glycosyl acceptor comprises an alcohol, a thiol, or an amine.
16. The method of claim 1 , wherein the glycosyl acceptor is a monosaccharide, a disaccharide, an oligosaccharide, or a polysaccharide, each comprising at least one —OH, —SH, or primary or secondary amino group.
17. The method of claim 1 , wherein the first solvent is selected from the group consisting of tetrahydrofuran (THF), diglyme, and a combination of THF and diglyme.
18. The method of claim 1 , wherein the second solvent is selected from the group consisting of tetrahydrofuran (THF), diglyme, and a combination of THF and diglyme.
19. The method of claim 1 , wherein the first solvent is the same as the second solvent.
20. The method of claim 1 , wherein the sulfonylating agent is tosyl 4-nitroimidazole.
21. The method of claim 1 , wherein the sulfonylating agent is benzenesulfonyl 4-nitroimidazole.
22. The method of claim 1 , wherein the sulfonylating agent is p-toluenesulfonic anhydride.