Acid zeolites as efficient catalysts for O- and S-glycosylation

We report herein the first regioselective synthesis of β-galactofuranosides by Fischer glycosidation of GalNAc with methanol catalyzed by HY, HZSM-5 and HBEA acid zeolites. The zeolite HY (Si/Al ratio 3.1) was the most efficient catalyst, leading to the highest yield of methyl β-galactofuranoside, isolated as its acetylated or isopropylidene derivatives, indicating that with large pore zeolites, the reaction efficiency depends upon the concentration of the zeolite acid sites and its hydrophilicity. However, the best regioselectivity for β-galactofuranoside versus β-galactopyranoside was obtained with the medium pore zeolite HZSM-5, which also led to the lowest starting material conversion, suggesting that both the zeolite pore size and topology are determinant for the obtained results. Furthermore, these acid zeolites proved to be efficient catalysts to transform 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-d-arabino-hex-1-enitol (6) (3,4,6-tri-O-benzyl-d-glucal) exclusively in the 2,3-unsaturated-O- and -S-α-d-glycosides by Ferrier rearrangement, in moderate yield. For this reaction, the number of acid sites was the key factor for the reaction yield, being HY (Si/Al ratio 3.1) also the most effective zeolite.

Graphical abstractThe zeolites HY, HBEA and HZSM-5 were investigated for glycosylation using two glycosyl donor types: N-acetylgalactosamine and a glycal. Regioselectivity for the furanoside form occurred in the Fischer glycosidation with all the catalysts. They also proved to be effective in transforming a benzyl-protected glycal into Ferrier products. Their efficiency depended mainly upon their Brönsted acid sites concentration and hydrophilicity for both reactions.Figure optionsDownload full-size imageDownload as PowerPoint slide