Conformationally restricted 3,5-O-(di-tert-butylsilylene)-d-galactofuranosyl thioglycoside donor for 1,2-cis α-d-galactofuranosylation

• A conformationally restricted 3,5-O-di-tert-butylsilylene-β-d-thiogalactofuranoside donor was synthesized.
• Unusual chemical behavior was observed after the introduction of 3,5-O-DTBS group.
• Moderate to high 1,2-cis stereoselectivity was obtained with p-NO2PhSCl/AgOTf as a promoting system.
• α-d-Galf-(1→6)-d-Man linkage was achieved with complete diastereoselectivity by preactivation of the donor.

A conformationally restricted 2-O-benzyl-3,5-O-di-tert-butylsilylene-β-d-thiogalactofuranoside donor was prepared from benzyl α-d-galactofuranoside and its donor capability was studied for stereoselective 1,2-cis α-d-galactofuranosylation. An unusual chemical behavior in benzylation and hydrogenolysis reactions was observed after the introduction of the 3,5-O-di-tert-butylsilylene protecting group into the galactofuranosyl moiety. The influence of the solvent, temperature, and activating system was evaluated. The NIS/AgOTf system, widely used in 1,2-cis β-arabinofuranosylation, was not satisfactory enough for 1,2-cis galactofuranosylation. However, moderate to high α-selectivity was obtained with all the acceptors employed when using p-NO2PhSCl/AgOTf as a promoting system, in CH2Cl2 at −78 °C. The order of the addition of the reactants (premixing or preactivation) did not affect substantially the stereochemical course of the glycosylation reaction. The α-d-Galf-(1→6)-d-Man linkage was achieved with complete diastereoselectivity by preactivation of the conformationally constrained thioglycoside donor.

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