Fluorinated Protective Groups for On-Resin Quantification of Solid-Phase Oligosaccharide Synthesis with 19F NMR Spectroscopy
✍ Scribed by Mickael Mogemark; Mikael Elofsson; Jan Kihlberg
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 181 KB
- Volume
- 3
- Category
- Article
- ISSN
- 1439-4227
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✦ Synopsis
Solid-phase synthesis is an attractive approach for the generation of large numbers of compounds for biological studies, for instance in the pharmaceutical industry. [1] In addition, automated procedures for solid-phase synthesis of oligopeptides and oligonucleotides have been of major importance in developing an understanding of the functions of proteins and nucleic acids in the processes of life. As compared to knowledge about these two biopolymers, the roles played by carbohydrates in different glycoconjugates in nature are less well understood. [2] Unfortunately, the difficulties associated with the synthesis of oligosaccharides constitute a major impediment for the development of glycobiology. [3] For instance, the assembly of complex oligosaccharides on solid support or in solution is still a considerable challenge for all but a few laboratories.
Although major advances in the solid-phase synthesis of oligo-and polysaccharides have been made during the past few years, [4] the lack of simple and powerful analytical techniques for on-resin validation of the chemistry involved is a significant limitation. [5] In general, the use of nondestructive methods, such as IR and NMR spectroscopy, for elucidating reactions directly on the solid phase constitutes the most attractive approach. [6,7] However, applications of these techniques in solid-phase oligosaccharide synthesis are rare and include the use of highresolution magic-angle-spinning NMR spectroscopy, [8] as well as employment of 13 C-enriched acetyl protective groups. [9,10] These methods are somewhat restricted by costs and the requirement for specialized NMR spectroscopy equipment. On the other hand, fluorinated reagents corresponding to the most common protective groups used in oligosaccharide synthesis are commercially available and are usually cheap. Use of saccharide building blocks that carry fluorinated protective groups should therefore allow optimization of solid-phase oligosaccharide synthesis by using gel-phase 19 F NMR spectroscopy. Gel-phase 19 F NMR spectroscopy has several favorable properties including high sensitivity (the natural abundance of 19 F is 100 %) and a wide dispersion of the 19 F chemical shifts. Hence, magic-angle spinning is not required and high-quality spectra can be obtained in a couple of minutes with a conventional NMR spectrometer. [11±16] To investigate the potential of 19 F NMR spectroscopy for monitoring solid-phase oligosaccharide synthesis we have undertaken the synthesis of the a-Gal epitope (Gal(a1-3)-Gal(b1-4)Glc), which is responsible for hyperacute rejection in xenotransplantation of porcine organs. [17] The synthetic sequence started with immobilization of glycoside A (Scheme 1) on the linker-loaded ArgoGel resin 1 [15] through an ester linkage [18] to afford resin 2 (Scheme 2). The outcome of the