Comparative studies on the O-sialylation with four different α/β-oriented (N-acetyl)-5-N,4-O-carbonyl-protected p-toluenethiosialosides as donors

• The sialylations of four p-toluenethiosialoside donors were thoroughly studied.
• The acceptor amount and the promoter have great influence on the sialylation.
• The configuration of N-acetylated sialyl donors has little effect on the coupling.
• The N-deacetylated α/β sialyl donors show complex sialylation profiles.

Four types of 5-N,4-O-carbonyl-protected p-toluenethiosialosides were synthesized and their couplings with different acceptors were thoroughly investigated. The results indicate that the sialyl donor structure, the amount of glycosyl acceptor, and the detailed promotion conditions have great influence on the sialylation stereoselectivties and product yields. Under the (p-Tol)2SO/Tf2O activation conditions, the glycosylations with simple alcohols provided declined α-selectivities and higher yields with increasing the amounts of acceptors from 1.1 equiv to 2.0 equiv. However, the outcome of same sialylation was independent of the relative amounts of sugar alcohol acceptors. With NIS/TfOH as promoter, the α-selectivities of the sialylations were significantly improved compared with the cases activated by (p-Tol)2SO/Tf2O. In general, the difference in configuration of N-acetylated sialyl donors (D2 and D4) has little effect on the sialylation yield and stereoselectivity. In contrast, the N-deacetylated α/β sialyl donors (D1 and D3) show complex sialylation profiles with different acceptors.

Figure optionsDownload as PowerPoint slide