The α-Glycosidation of Partially Unprotected N-Acetyl and N-Glycolyl Sialyl Donors in the Absence of a Nitrile Solvent Effect.

Abstract

The synthesis of α-sialosides is one of the most difficult reactions in carbohydrate chemistry and is considered to be both a thermodynamically and kinetically disfavored process. The use of acetonitrile as a solvent is an effective solution for the α-selective glycosidation of N-acetyl sialic acids. In this report, we report on the α-glycosidation of partially unprotected N-acetyl and N-glycolyl donors in the absence of a nitrile solvent effect. The 9-O-benzyl-N-acetylthiosialoside underwent glycosidation in CH2 Cl2 with a good α-selectivity. On the other hand, the 4,7,8-O-triacetyl-9-O-benzyl-N-acetylthiosialoside was converted to β-sialoside as a major product under the same reaction conditions. The results indicate that the O-acetyl protection of the sialyl donor was a major factor in reducing the α-selectivity of sialylation. After tuning of the protecting groups of the hydroxy groups at the 4,7,8 position on the sialyl donor, we found that the 9-O-benzyl-4-O-chloroacetyl-N-acetylthiosialoside underwent sialylation with excellent α-selectivity in CH2 Cl2 . To demonstrate the utility of the method, straightforward synthesis of α(2,9) disialosides containing N-acetyl and/or N-glycolyl groups was achieved by using the two N-acetyl and N-glycolyl sialyl donors.