Water-promoted Synthesis of Stereoselective Oxazoline-fused Saccharides and Construction for 1, 2-cis Glycosylamines of Multi-modifications of Polyhydroxyl groups

Abstract

The multi-modifications of polyhydroxyl groups and the stereoselective formation of 1,2-cis glycosidic bonds are difficult in glycochemistry. Herein we disclosed a concise synthesis of the oxazoline-fused saccharides (oxazolinoses) from acetyl saccharides and benzonitriles under acidic conditions promoted by the stoichiometric water. The oxazolinoses can be easily converted into 1,2-cis glycosylamines with differentiated modifications at 2,3-positions on the saccharide ring in few steps and the 1-NH2 can further be simply transformed to the 1-OH. Oxazolinoses can also be directly used to synthesize complex chiral molecules such as schisandrins. Saccharides screening have shown that the oxazolinoses could be synthesized from various monosaccharides and oligosaccharides. Accordingly, 1-α- or 1-β-1,2-cis glycosylamines can be obtained from different oxazolinoses which are 1,2-cis stereoselectivity controlled by neighboring group participation. The density functional theory (DFT) calculations have revealed the origin of the stereoselectivity and the key role of water.