Synthesis and Evaluation of Fluorinated Benzyl Ethers as Alternate Protecting Groups for Enhanced NMR Resolution in Oligosaccharide Synthesis

Abstract

Oligosaccharides have been playing an important role in biological systems. Synthesis of oligosaccharides requires the protection from hydroxyl groups present in the corresponding monosaccharide units. The existing methods of protection have drawbacks, including formation of anomeric mixtures, change in hydrophilicity or lipophilicity and solubility of the products, participation of the protecting groups in the reactions of the core of monosaccharide units, problems associated with chemoselectivity, regioselectivity and overall stereochemical outcomes of reactions. Additionally, there has been a spectral overlap of these protecting groups with carbohydrate core, which yielded more complex spectra. Therefore, the identification and synthesis of suitable alternative protecting groups have received attention in the oligosaccharide synthesis. The objective of the present study was to synthesize various fluorinated benzyl ethers of methyl-α-D-mannopyronoside and to evaluate these ethers as the alternative protecting groups for enhancing NMR resolution in the oligosaccharide synthesis. Various fluorinated benzyl ethers of methyl-α-D-mannopyronoside were prepared through the reaction of methyl-α-D-mannopyronoside with various fluorinated benzyl bromides by using Williamson ether synthesis method. Spectral analysis of these fluorinated benzyl ethers showed that the peaks of methylene carbons shifted to a value of 10-20 parts per million (ppm) to a high field region in the ¹³C NMR, compared to the non-fluorinated benzyl ether. As a result, the spectral complexity decreased and enhanced the spectral resolution. In this study, we concluded that fluorinated benzyl ethers could be a suitable alternative to the non-fluorinated benzyl ethers to protect the hydroxyl groups of monosaccharides in the synthesis of oligosaccharides.