Regioselective 5-O-Opening of Conformationally Locked 3,5-O-Di-tert-butylsilylene-d-galactofuranosides. Synthesis of (1→5)-β-d-Galactofuranosyl Derivatives

Abstract

The use of thiogalactofuranoside as donors for the construction of internal Galf containing oligosaccharide is limited, probably due to the difficulty to functionalize thiogalactofuranoside derivatives showing O-2, O-3, and O-5 with similar reactivity. An efficient method for complete regioselective 5-O-opening of conformationally restricted 3,5-O-di-tertbutylsilylene-D-galactofuranoside derivatives was developed. The use of a solution nBu4NF (1.1 equiv) in CH2Cl2 on 6 gave the 5-OH free derivative 10 as the only product (90%). 3-O-Di-tert-butylhydroxysilyl derivative 10 was stable upon purification and glycosylation reaction. Preactivation of conformationally restricted thioglycoside 6 employing p-NO2-benzensulfenyl chloride/AgOTf followed by condensation over the 5-OH thioglycoside acceptor 10 gave the corresponding disaccharide 12 without autocondensation byproduct. Regioselective 5-O-deprotection was also successfully performed over the (1→5)-β-D-galactofuranosyl di- and trisaccharide derivatives 12 and 13. This methodology allowed the differentiation between the secondary hydroxyl groups OH-3 and OH-5 of 1,2-cis or 1,2-trans D-galactofuranoside derivatives, and it still constitutes an innovative approach to access oligosaccharides of pharmacological importance.