The chemical synthesis of sialosides is complicated mainly by the presence of a destabilizing carboxylic group at C-1 and the lack of hydroxyl group at C-3. Thus, sialylation reactions are often plagued by side reactions (hydrolysis and elimination) and the presence of the unnatural b-anomer.
To improve the efficiency of sialylations, different methodologies have been investigated in the past years, including structural modifications at C-1, C-3 and C-5 as well as the solvent effect.
Recently, C-5 modification of thiosialosyl donors as oxazolidinone trans-fused ring proved to enhance dramatically yields and stereoselectivities in sialylations for the synthesis of a(2-8) and a(2-9) dimers as well a(2-6) and a(2-3) linkages with galactosyl acceptors.
Despite notable achievements for the synthesis of alpha sialoside have been made, sialylation reactions often require low temperatures (-40-78 ºC) and the use of acetonitrile as a solvent. Herein we report that a oxazolidinone C-5 protected donor gives for the synthesis of a(2-6) sialosides excellent stereoselectivities and yields in the presence of a wide variety of solvents and temperatures, obtaining in some cases a-stereoselectivity even at room temperature.