Conformationally constrained 3,5-O-(di-tert-butylsilylene)-D-galactofuranosyl donor derivative. Glycosylation studies.

CAROLA GALLO -RODRIGUEZ; MARIANO J. TILVE

Oslo, Noruega

Congreso; 23th International Carbohydrate Symposium; 2008

Intenational Carbohydrate Organization

The synthesis of 1,2-cis galactofuranosides is a challenge due, among other factors, to the lesser anomeric effect in comparison to the pyranose form. Whereas the selectivity in the formation of a 1,2-trans glycoside is controlled by the anchimeric participation of an ester group in C-2; the formation of a 1,2-cis linkage requires, at least, a non-participant group. Recently, we have synthesized a di- and a trisaccharide alditols isolated from Clostridium thermocellum and Bacteriodes cellulosolvens with α-D-Galf, employing O-(2,3,5,6-tetra-O-benzyl-D-galactofuranoside) trichloroacetimidate as donor with moderate diastereoselectivities in the glycosylation reactions [1]. The presence of α-D-Galf unit in pathogenic microorganisms such as Streptococcus pneumoniae 22F, Escherichia coli O167, and Paracoccidioides brasiliensis prompted us the synthesis of oligosaccharides aimed at contributing to biosynthetic studies.Woerpel et al. suggested that the nucleophilic attack to furanose oxocarbenium ions, in C-glycosylations, ocurrs from inside the envelope (inside attack). Mixtures are obtained with arabinofuranose derivatives due to the stereoelectronic influence of C-2 and C-3 substituents in a trans relationship, and in conformational equilibrium [2]. The introduction of a 3,5-O-di-tert-butylsilylene group in L-arabinose locks the ring in a E3 conformation, thus the inside attack of the acceptor occurs from the a face, giving rise to a 1,2-cis linkage [3]. Moreover, Crich et al. have employed the sulfoxide and thioglycoside glycosylation methods in similar derivatives of D-arabinose [4]. Taking into account the stereochemical relationship between arabinose and galactose, the synthesis of a conformationally restricted derivative donor was proposed for the construction of 1,2-cis galactofuranosyl linkages. Compound 1 was synthesized from allyl α-D-galactofuranoside [5] in 7 steps. Glycosylation reactions were performed with several acceptors and stereoselectivities obtained showed an important dependency on the temperature and the nature of the acceptor.