378 Solvent and C-5 Effect in Sialylations

Friday, November 6, 2009: 10:30 AM
Angus (Camino Real Hotel)
Cristina De Meo, Associate Professor , Chemistry, Southern Illinois University Edwardsville, Edwardsville, IL
Bonnie Gulley , Chemistry, Southern Illinois University Edwardsville, Edwardsville, IL
Daniel Mueller , Chemistry, Southern Illinois University Edwardsville, Edwardsville, IL
Uvege Priyadarshani , Chemistry, Southern Illinois University Edwardsville, Edwardsville, IL
Nathan Ginder , Chemistry, Southern Illinois University Edwardsville, Edwardsville, IL
Sialic acid containing glycoconjugates (sialosides) are important synthetic targets for the design of drugs and vaccines. In fact, the exposed position of these molecules enables them to numerous biological phenomena, ranging from cell-cell adhesion to cell growth regulation, to immune response and oncogenesis.

 

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.