Facile Synthesis of per-O-tertbutyldimethylsilyl-beta-D-Galactofuranose and Efficient Glycosylation via the Galactofuranosyl Iodide

CARLA MARINO; LUCIANA BALDONI

Oslo, Noruega

Simposio; XXIV International Carbohydrate Symposium; 2008

Highly immunogenic galactofuranosyl residues are present in glycoconjugates of many pathogenic bacteria, fungi, and protozoan parasites. The fact that D-Galf is essential for the survival or virulence of various pathogenic bacteria, but it is absent in higher eukaryotes, prompted investigation on its biosynthetic pathways. Therefore, the synthesis of oligosaccharides containing D-Galf units is an area of active research.             The compounds most frequently used as precursors of D-Galf units in oligosaccharides and glycoconjugates are the peracylated derivatives. With the exception of the perbenzoylated derivative, which can be obtained in one step and it is purified from the pyranosic forms by fractionated crystallization, the other precursors need at least three reaction steps and the corresponding purifications. Our continuing interest in the development of methodologies for the synthesis of galactofuranose derivatives led us to explore the synthesis of per-O-silylated derivatives of D-Galf. Herein we report the easy preparation of a new precursor of D-galactofuranosyl moieties, the persilylated derivative 1, obtained as a crystalline product in one step from D-galactose. As protective group, TBS combines stability under a wide range of reaction conditions and it is susceptible to easy removal by highly specific reagents.             On the other hand, a wide variety of successful glycosylation reactions have been developed for the assembly of D-Galf units in the synthesis of oligosaccharides and glycoconjugates. Nevertheless, the development of new efficient methodologies is still desirably for design novel strategies. With compound 1 in hand, we decided to investigate the glycosylation reaction promoted by TMSI, extensively used for glycopyranoses. Thus, the galactofuranosyl iodide 2 was generated in situ and coupled with simple alcohols in the presence of EtN(iPr)2 as an acid scavenger.             A number of coupling experiments have been carried out with selected glycosyl acceptors to afford precursors of relevant galactofuranose-containing disaccharides. Aspects of stability of different protective groups and regioselectivity on the acceptors will be discussed.