Mono- vs. di-fluorous-tagged glucosamines for iterative oligosaccharide synthesis

Fluorous-tagged protecting groups are attractive tools for elongating carbohydrate chains in oligosaccharide synthesis. To eliminate the accumulation of failed sequences during automated oligosaccharide synthesis conditions, an additional C8F17 ester derived protecting group was attached to the glycosyl donor to better retain the desired doubly tagged glycosylation product on fluorous solid-phase extraction (FSPE) cartridges. Initial studies show that the double-fluorous-tagging strategy offers a robust enough separation using a commercial FSPE cartridge using simple gravity filtration to separate the desired product from the singly fluorous-tagged starting materials and their decomposition products. In addition, removal of the fluorous acetate and its by-products after sodium methoxide treatment and neutralization required only dissolution of the desired sugar in toluene and subsequent removal of the toluene layer from the denser fluorous by-products.

A light fluorous acetate protecting group on an oligoglucosamine glycosyl donor allowed facile separation by FSPE of the resulting double-fluorous-tagged glycosylation product from the single-fluorous-tagged acceptor as well as donor by-products. This double-fluorous-tagging strategy offers a robust simple separation to eliminate failed glycosylation sequences in solution-based oligosaccharide synthesis.Figure optionsDownload as PowerPoint slide