Compositions and methods for sulfation of carbohydrates
In one aspect, the disclosure relates to a facile strategy to introduce electron-deficient aryl sulfate diesters to silylated hydroxyl groups of carbohydrates and amino acids, among other substrates, wherein selective hydrolysis and the removal of an electron-deficient aromatic group allows for the efficient generation of sulfated carbohydrates, peptides, and other compounds. The incorporation of electron-deficient aryl sulfate diesters in the early stage of the synthesis of glycans, peptides, and the like, disclosed herein avoids time-consuming protecting group manipulations, simplifies the purification of sulfated products, and improves the overall yield and efficiency. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
1. A method for synthesis of masked sulfate diesters, the method comprising contacting a substrate having at least one hydroxyl group with an aryl fluorosulfate, a silylating reagent, and a base catalyst in a solvent to produce a product sulfate diester, and wherein the substrate comprises a sugar, a sugar comprising at least one protected hydroxyl group, a polysaccharide, a glycosaminoglycan, or a combination thereof.
2. The method of claim 1 , wherein the substrate comprises
or a combination thereof.
3. The method of claim 1 , wherein the silylating reagent comprises trimethylsilyl chloride (TMSCI), bis(trimethylsilyl)amine (HMDS), or a combination thereof.
4. The method of claim 1 , wherein the aryl fluorosulfate comprises
or a combination thereof.
5. The method of claim 1 , wherein the base catalyst comprises 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), tert-butylamino-tri(pyrrolidino)phosphorane (BTPP), 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP), 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), triazabicyclodecene (TBD), imidazole, or a combination thereof.
6. The method of claim 1 , wherein the masked sulfate diester comprises from about 1 to about 3 sulfate diester linkages.
7. The method of claim 1 , wherein the masked sulfate diester comprises
or a combination thereof.
8. The method of claim 1 , wherein the substrate is first contacted with silylating reagent and then contacted with the aryl fluorosulfate and the catalyst.
9. The method of claim 1 , wherein the substrate is contacted with the aryl fluorosulfate, catalyst, and the silylating reagent simultaneously.