Use of Ionically Tagged Glycosyl Donors in the Synthesis of Oligosaccharide Libraries

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2009 Oct 20

PMID 19837587

Authors

Eun Ju Kim

Gary R Gray

Affiliations

Soon will be listed here.

Abstract

We have developed a new procedure based on the random glycosyl reaction of a partially benzoylated glycosyl acceptor with a glycosyl donor containing a 4,6-O-(4-methoxycarbonylbenzylidene) protecting group as a masked/caged ion-tag. Glycosylated products are ionically tagged by saponification of the methyl ester and the use of this anion-tag greatly simplifies the separation of the desired oligosaccharides from unreacted or excess glycosyl acceptors as well as from over-glycosylated oligosaccharides. In addition, the use of partially benzoylated acceptors greatly improves their solubility in dichloromethane increasing the yield of product formation and, also, of altering the distribution of positional isomers in favor of products derived by reaction of the donors at hydroxyl groups which otherwise would be considerably less reactive. Using this new approach in random glycosyl reactions, several oligosaccharide libraries were readily prepared in overall yields of 60-70% and the individual positional isomers present in the libraries were identified using the 'reductive-cleavage' method.

References

Paulson J . Glycoproteins: what are the sugar chains for?. Trends Biochem Sci. 1989; 14(7):272-6. DOI: 10.1016/0968-0004(89)90062-5. View

Cundell D, Tuomanen E . Receptor specificity of adherence of Streptococcus pneumoniae to human type-II pneumocytes and vascular endothelial cells in vitro. Microb Pathog. 1994; 17(6):361-74. DOI: 10.1006/mpat.1994.1082. View

Dube D, Bertozzi C . Glycans in cancer and inflammation--potential for therapeutics and diagnostics. Nat Rev Drug Discov. 2005; 4(6):477-88. DOI: 10.1038/nrd1751. View

Love D, Hanover J . The hexosamine signaling pathway: deciphering the "O-GlcNAc code". Sci STKE. 2005; 2005(312):re13. DOI: 10.1126/stke.3122005re13. View

Elvebak 2nd L, Cha H, McNally P, Gray G . Authentic standards for the reductive-cleavage method. The positional isomers of partially methylated and acetylated or benzoylated 1,5-anhydro-D-mannitol. Carbohydr Res. 1995; 274:71-83. DOI: 10.1016/0008-6215(95)00082-5. View

Harris S, Varma V, Pinto B . Convergent synthesis of an elusive hexasaccharide corresponding to the cell-wall polysaccharide of the beta-hemolytic Streptococcus group A. Carbohydr Res. 1993; 245(2):245-57. DOI: 10.1016/0008-6215(93)80075-p. View

Tsuchiya T . Chemistry and developments of fluorinated carbohydrates. Adv Carbohydr Chem Biochem. 1990; 48:91-277. DOI: 10.1016/s0065-2318(08)60032-3. View

Dwek R . Glycobiology: Toward Understanding the Function of Sugars. Chem Rev. 1996; 96(2):683-720. DOI: 10.1021/cr940283b. View

Helenius A, Aebi M . Intracellular functions of N-linked glycans. Science. 2001; 291(5512):2364-9. DOI: 10.1126/science.291.5512.2364. View

10.

Liang R, Yan L, Loebach J, Ge M, Uozumi Y, Sekanina K . Parallel synthesis and screening of a solid phase carbohydrate library. Science. 1996; 274(5292):1520-2. DOI: 10.1126/science.274.5292.1520. View

11.

Thompson L, Ellman J . Synthesis and Applications of Small Molecule Libraries. Chem Rev. 1996; 96(1):555-600. DOI: 10.1021/cr9402081. View

12.

ROLF D, Gray G . Analysis of the linkage positions in D-fructofuranosyl residues by the reductive-cleavage method. Carbohydr Res. 1984; 131(1):17-28. DOI: 10.1016/0008-6215(84)85399-9. View

13.

Matsuzaki Y, Nunomura S, Ito Y, Sugimoto M, Nakahara Y, Ogawa T . Stereocontrolled synthesis of GD2. Carbohydr Res. 1993; 242:C1-6. DOI: 10.1016/0008-6215(93)80049-k. View

14.

Elvebak 2nd L, Gray G . Authentic standards for the reductive-cleavage method. The positional isomers of partially methylated and acetylated or benzoylated 1,5-anhydro-D-glucitol. Carbohydr Res. 1995; 274:85-97. DOI: 10.1016/0008-6215(95)00094-a. View

15.

Ding Y, Liu Y . Stereoselective syntheses of acetylated o-tolyl 1-thioglycosides. Carbohydr Res. 1991; 209:306-10. DOI: 10.1016/0008-6215(91)80168-m. View

16.

Elvebak 2nd L, Abbott C, Wall S, Gray G . Authentic standards for the reductive-cleavage method. The positional isomers of partially methylated and acetylated or benzoylated 1,5-anhydro-D-galactitol. Carbohydr Res. 1995; 269(1):1-15. DOI: 10.1016/0008-6215(94)00353-h. View

17.

Gordon E, Barrett R, Dower W, Fodor S, Gallop M . Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions. J Med Chem. 1994; 37(10):1385-401. DOI: 10.1021/jm00036a001. View

18.

Gallop M, Barrett R, Dower W, Fodor S, Gordon E . Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries. J Med Chem. 1994; 37(9):1233-51. DOI: 10.1021/jm00035a001. View

19.

Bowie J, Trescony P, Gray G . Analysis of linkage positions in Saccharomyces cerevisiae D-mannans by the reductive-cleavage method. Carbohydr Res. 1984; 125(2):301-7. DOI: 10.1016/0008-6215(84)85165-4. View

20.

Ding Y, Labbe J, Kanie O, Hindsgaul O . Towards oligosaccharide libraries: a study of the random galactosylation of unprotected N-acetylglucosamine. Bioorg Med Chem. 1996; 4(5):683-92. DOI: 10.1016/0968-0896(96)00064-8. View