Solid-phase and solution-phase synthesis of glycosylphosphatidylinositol glycans

• US 7,943,594 B2
• Filed: 07/10/2003
• Issued: 05/17/2011
• Est. Priority Date: 07/10/2002
• Status: Expired due to Fees

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Massachusetts Institute of Technology
• Inventors: Snyder, Daniel A., Seeberger, Peter H., Hewitt, Michael C.
• Primary Examiner(s): Jiang; Shaojia Anna
• Assistant Examiner(s): Henry; Michael C
• Application Number:
  US10/520,963
• Publication Number:
  US 20060089330A1
• Time in Patent Office: 2,868 Days
• Field of Search: 514/54, 514/25, 514/35, 514/53, 514/62, 536/17.2, 536/18.7, 536/124
• US Class Current: 514/54
• CPC Class Codes: A61P 33/02 Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07H 15/203 Monocyclic carbocyclic rings other than cyclohexane rings; Bicyclic carbocyclic ring systems
• CPC Class Codes: C07H 15/207 Cyclohexane rings not substituted by nitrogen atoms, e.g. kasugamycins
• CPC Class Codes: C08B 37/006 Heteroglycans, i.e. polysaccharides having more than one sugar residue in the main chain in either alternating or less regular sequence; Gellans; Succinoglycans; Arabinogalactans; Tragacanth or gum tragacanth or traganth from Astragalus; Gum Karaya from Sterculia urens; Gum Ghatti from Anogeissus latifolia; Derivatives thereof

Abstract

One aspect of the present invention relates to solution-phase approaches to GPI synthesis. Another aspect of the present invention relates to key building blocks, and syntheses thereof, useful for GPI assembly. Yet another aspect of the invention relates to an automated method for the synthesis of GPIs and fragments thereof.

Claims

1. A compound represented by formula I:

2. The compound of claim 1, wherein n is 3.

3. The compound of claim 1, wherein R is H.

4. The compound of claim 1, wherein R¹ and R² taken together are P(O)OR⁵.

5. The compound of claim 1, wherein R³ is N₃.

6. The compound of claim 1, wherein R³ is —

NH₃X.

7. The compound of claim 1, wherein R⁴ represents independently for each occurrence —

CH₂Ph, or —

Si(alkyl)₃.

8. The compound of claim 1, wherein R⁴ represents independently for each occurrence —

CH₂Ph, or —

P(O)OR⁵; and

R⁵ is an optionally substituted alkyl group.

9. A compound represented by formula II:

10. The compound of claim 9, wherein n is 3.

11. The compound of claim 9, wherein m is 3.

12. The compound of claim 10, wherein R represents independently for each occurrence —

CH₂-aryl or —

Si(alkyl)₃.

13. The compound of claim 10, wherein R represents independently for each occurrence benzyl or —

Si(iPr)₃.

14. The compound of claim 10, wherein R¹ is trichloroacetimidate and R represents independently for each occurrence benzyl or —

Si(iPr)₃.

15. The compound of claim 10, wherein said compound of formula II is selected from the group consisting of:

16. A compound represented by formula I:

17. The compound of claim 16, wherein R is H;

R¹ and R² taken together are P(O)OR⁵;

R⁴ is H; and

R⁶ is -P(O)(OR⁵)₂.

18. A compound represented by formula I: