Sialic acid is a principal building block for mono, di, or polysaccharides that are found at the outermost of the cell surface. Due to the presence of multiple hydroxyl groups, modification creates a diverse family of glycoconjugates. O-Acetylation is a common modification and 9-O-acetyl sialic acid is the most common form found in human biology. However, 4-O-acetyl, 4,9-O-diacetyl- or 7,9-O-diacetyl sialic acids have also been characterized as receptors for viruses or in cancer progression. Synthesizing these derivatives is challenging because of the multiple protection and deprotection steps required and purification is difficult due to similar polarity of desired products and by products. Our lab has established a Regioselective Silyl Exchange Technology (ReSET) method to acetylate mono, di, tri, and tetra O-acetylated sialic acids using microwave radiation. We also characterized and assigned the silicon signal to the per-silylated sialic acid intermediates. The silicon NMR allows one to see the order of silyl-acetyl group exchange and the chemistry behind each exchange. In this presentation, we are reporting silicon NMR experiments of five silyl-acetyl sialic acid derivatives in three different solvents. Several trends were observed from the experiments of the five derivatives allowing chemical exchange to be correlated with 29Si chemical shift. Meanwhile, the silicon group at C7 (Si7) consistently appeared the furthest downfield and was the only silicon group not to exchange under the established conditions. We also found that the signals in pyridine-d5 and benzene-d6 are more upfield compared to chloroform d3. Monitoring silicon exchange will help to establish continuous flow chemistry conditions to selectively acetylate sialic acid analogs with little or no by products in future projects.

Silicon NMR approach to determine the chemistry of acetylation per-O-TMS sialic acid derivatives

ACS Spring 2022

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