Method for 2-sulfation of glycosides

1. A method for sulfating an iduronate glycoside at the 2-position, comprising:

(a) treating an iduronate glycoside having hydroxyl groups at positions 2 and 4 in a cis relationship with a tin reagent to provide a glycoside 2,4-stannylene acetal; and

(b) treating the 2,4-stannylene acetal with a sulfating agent to selectively provide a 2-sulfated iduronate glycoside.

2. The method of claim 1 , wherein the 2-sulfated glycoside is sulfated at the 2-position with a selectivity greater than 90%.

3. The method of claim 1 , wherein the 2-sulfated glycoside is sulfated at the 2-position with a selectivity greater than 95%.

4. The method of claim 1 , wherein the glycoside is an α-L-iduronate glycoside.

5. The method of claim 1 , wherein the tin reagent is a dialkyltin IV oxide.

6. The method of claim 1 , wherein the tin reagent is dibutyltin (IV) oxide.

7. The method of claim 1 , wherein the sulfating agent is sulfur trioxide.

8. The method of claim 1 , wherein the sulfating agent is a sulfur trioxide complex selected from the group consisting of sulfur trioxide trimethylamine complex, sulfur trioxide pyridine complex, and sulfur trioxide N,N-dimethylformamide complex.

9. The method of claim 1 , wherein the glycoside has the formula:

10. The method of claim 1 , wherein the 2-sulfated iduronate glycoside has the formula:

11. The method of claim 10 further comprising saponifying the 2-sulfated glycoside methyl ester to provide a 2-sulfated iduronate glycoside having the formula:

12. The method of claim 1 , wherein the iduronate glycoside has the formula:

wherein the glycoside forms a parent ion when subjected to electrospray ionization-tandem mass spectrometry,

M is a moiety that cleaves from the parent ion to provide a fragment ion on collision-induced dissociation,

L covalently links M to the iduronate glycoside moiety, and

R is a C1-C6 alkyl group.

13. The method of claim 1 , wherein the 2-sulfated iduronate glycoside has the formula:

wherein the sulfated iduronate glycoside forms a parent ion when subjected to electrospray ionization-tandem mass spectrometry,

M is a moiety that cleaves from the parent ion to provide a fragment ion on collision-induced dissociation,

L covalently links M to the iduronate glycoside moiety,

R is a C1-C6 alkyl group, and

X is hydrogen, an ammonium ion, or a metal ion.

14. The method of claim 13 further comprising saponifying the 2-sulfated glycoside ester to provide a 2-sulfated iduronate glycoside having the formula:

wherein the sulfated iduronate glycoside forms a parent ion when subjected to electrospray ionization-tandem mass spectrometry,

M is a moiety that cleaves from the parent ion to provide a fragment ion on collision-induced dissociation,

L covalently links M to the iduronate glycoside moiety, and

X is hydrogen, an ammonium ion, or a metal ion.

15. The method of claim 13 , wherein M is a butyloxycarbonyl [C 4 H 9 C(═O)—].

16. The method of claim 13 , wherein L is —NH—(CH 2 ) n —NHC(═O)CH 2 —, where n is 1-8.

17. The method of claim 13 , wherein the ammonium ion is trimethylammonium.

18. The method of claim 13 , wherein the metal ion is a sodium ion.