Glycosylation Reactions Using Phenyl(trifluoroethyl)iodonium Salts

• US 20150099870A1
• Filed: 10/03/2014
• Published: 04/09/2015
• Est. Priority Date: 10/04/2013
• Status: Active Grant

• Current Assignee: Trustees of Tufts College
• Original Assignee: Trustees of Tufts College
• Inventors: Bennett, Clay S., Chu, An-Hsiang A.
• Granted Patent: US 9,422,325 B2
• Time in Patent Office: Days
• US Class Current: 536/5
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• CPC Class Codes: C07H 15/18 Acyclic radicals, substituted by carbocyclic rings
• CPC Class Codes: C07H 15/203 Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
• CPC Class Codes: C07H 3/02 Monosaccharides
• CPC Class Codes: C07H 3/04 Disaccharides
• CPC Class Codes: C07H 3/06 Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
• CPC Class Codes: C07J 17/005 Glycosides
• CPC Class Codes: C07J 41/0055 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
• CPC Class Codes: C07J 41/0088 containing unsubstituted amino radicals
• CPC Class Codes: C08B 37/00 Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof cellulose D21; microbiological processes C12P

Abstract

Provided are methods for the preparation of glycosylation products, including those represented by formula I:

Sugar-O—R′  I

• • comprising the step of combining R′—OH, a glycosyl sulfide glycosyl donor (“thioglycoside donor”), a hypervalent iodine alkyl-transfer activating reagent, and a base. In an embodiment, the hypervalent iodine alkyl-transfer activating reagent is (phenyl(trifluoroethyl)iodonium triflimide).

Claims

1. A method of preparing a compound represented by formula I:

Sugar-O—

R′

 

 

I

comprising the step of combining R′

—

OH, a glycosyl donor of formula II, a reagent of formula III, and a base;

wherein

said base is selected from the group consisting of pyridine, pyrimidine, 2,6-lutidine, 2,6-di-tert-butylpyridine, 2,4,6-trimethylpyridine (collidine), diisopropylethylamine (DIPEA), 1,4-diazabicyclo[2.2.2]octane (DABCO), 1,8-Bis(dimethylamino)naphthalene (Proton Sponge), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and 2,4,6-tri-tert-butylpyrimidine (TTBP);

Sugar is an optionally protected monosaccharide or oligosaccharide;

O is an oxygen atom attached to an anomeric carbon atom of Sugar;

R′

is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, heteroaralkyl, and heterocyclyl;

or R′

—

OH is a steroid or an optionally protected monosaccharide, disaccharide, trisaccharide, tetrasaccharide, pentasaccharide, or hexasaccharide, wherein O is not bonded to an anomeric carbon atom of R;

formula II is represented by;

Sugar-S—

R¹ 

 

II

wherein

S is a sulfur atom attached to the anomeric carbon atom of Sugar;

R¹ is a phenyl, naphthyl, ethyl, or adamantyl group, each optionally substituted with one or more substituents independently selected from the group consisting of halo, alkyl, haloalkyl, perhaloalkyl, alkoxy, and cyano;

formula III is represented by;

2. The method of claim 1, wherein Sugar is an optionally protected monosaccharide, disaccharide, or trisaccharide.

3. The method of claim 1, wherein Sugar is an optionally protected monosaccharide.

4. The method of claim 1, wherein Sugar is a protected glucopyranoside.

5. The method of claim 1, wherein R′

is selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, and heteroaralkyl;

or R′

—

OH is a steroid or an optionally protected monosaccharide, disaccharide, trisaccharide, or tetrasaccharide.

6. The method of claim 1, wherein R′

—

OH is cholesterol.

7. The method of claim 1, wherein R′

—

OH is a protected monosaccharide or disaccharide.

8. The method of claim 1, wherein the OH group of R′

—

OH that forms a bond to the anomeric carbon atom of Sugar is the C3 or C6 hydroxyl of a protected monosaccharide or disaccharide.

9. The method of claim 1, wherein R′

—

OH is selected from the group consisting of

10. The method of claim 1, wherein R¹ is a phenyl or naphthyl group optionally substituted with one halo, alkyl, or haloalkyl.

11. The method of claim 1, wherein R¹ is an unsubstituted phenyl group.

12. The method of claim 1, wherein R² represents one or two substituents each independently selected from the group consisting of halo, alkyl, fluoroalkyl, and perfluoroalkyl.

13. The method of claim 1, wherein R² is absent.

14. The method of claim 1, wherein R³ is fluoroalkyl.

15. The method of claim 1, wherein R³ is 2,2,2-trifluoroethyl.

16. The method of claim 1, wherein X⁻

is selected from the group consisting of methanesulfonate, trifluoromethanesulfonate, benzenesulfonate, p-toluenesulfonate, bis(methanesulfonyl)amide, bis(trifluoromethanesulfonyl)amide, bis(benzenesulfonyl)amide, (trifluoromethanesulfonyl)(trifluoroacetyl)amide, and bis(p-toluenesulfonyl)amide.

17. The method of claim 1, wherein X⁻

is selected from the group consisting of bis(methanesulfonyl)amide, bis(trifluoromethanesulfonyl)amide, bis(benzenesulfonyl)amide, and bis(p-toluenesulfonyl)amide.

18. The method of claim 1, wherein X⁻

is bis(trifluoromethanesulfonyl)amide.

19. The method of claim 1, wherein the base is selected from the group consisting of pyridine, pyrimidine, 2,6-lutidine, 2,6-di-tert-butylpyridine, 2,4,6-trimethylpyridine (collidine), and 2,4,6-tri-tert-butylpyrimidine (TTBP).

20. The method of claim 1, wherein the base is 2,4,6-tri-tert-butylpyrimidine (TTBP).

21. The method of claim 1, wherein the glycosyl donor is selected from the group consisting of

22. The method of claim 1, wherein the reagent of formula III is

23. The method of claim 1, wherein Sugar is protected with one or more benzyl, para-methoxybenzyl, benzylidine, acetonide, methyl, acetyl, tert-butyloxycarbonyl, or silyl groups.