Sialylations reactions: Expanding the effect of silicon protecting groups at C-4.

As a part of a general research goal into evaluating the effect of O-protecting groups in sialylation reactions, we compared the reactivities of phenylthio α- and ß-sialyl donors protected at C-4 with tert-butyldimethyl silyl (TBDMS) and tri-isopropylsilyl (TIPS) groups in the coupling with primary and secondary galactosyl acceptors. The effect of the solvent and the donor's anomeric configuration were investigated and compared to previously published data. It is demonstrated that silicon groups at C-4 have a significant influence on sialylation reactions, and in general their overall performance is optimized with the use of acetonitrile.

Comparative Study on the Effects of Picoloyl Groups in Sialylations Based on Their Substitution Pattern.

A novel 8-O-picoloylated sialyl donor has been developed, and the performance of various picoloylated sialyl donors in glycosylations with primary glycosyl acceptors has been evaluated. 8-O-Picoloyl and 4,9-di-O-picoloyl sialyl donors produced moderate to excellent yields of disaccharides with complete α-stereoselectivities. Synergistic effects between picoloyl and the accompanying O-protecting groups (benzoyl vs acetyl) were evaluated, as well as the effects of triflic acid concentration on the 8-O-picoloyl donor. 1H NMR analysis was also carried out to assess differences in the hydrogen-bonding net between sialyl donors.

Facile and robust methods for the regioselective acylation of N-acetylneuraminic acid.

The stereoselective synthesis of sialic acid glycoconjugates is still a challenge in the field. Surprisingly, little is known on the regioselective O-substitution of sialic acids. Consequently, the effect of O-protecting groups and/or regioselectively protected building blocks in sialylations, remains practically unexplored. O-Picoloyl protecting groups have emerged as novel substituents that have a profound effect on sialylations. Recently, high stereoselectivities were obtained by introducing picoloyl groups at the C-4 and C-7/C-8 positions. However, to understand the relationship between the position of the picoloyl group and its exact effect in sialylations, a convenient access to a wider range of regioselectively picoloylated building blocks is needed. Reported herein is a new method that provides an accessible route to a wide array of regioselectively acylated building blocks. The regioselective introduction of picoloyl groups at various O-positions was achieved either by controlled direct picoloylation or by applying a modified ReSET methodology.