A 2,3-carbamate-bearing allyl galactosamine donor for the synthesis of repeating alfa-(1 4)-linked galactosamine units

The 1,2-cis-linked 2-amino-2-deoxy sugar structure is found in various oligosaccharides of biological importance. The repeating GalpNAc--(1→4)-GalpNAc unit constitutes for example an essential motif incorporated in a range of oligosaccharides, e.g. the repeating unit of the O-antigen moiety of the lipopolysaccharide from Escherichia Coli O142 or Sphaerotilus natans.[1] Vi antigen is instead a linear homopolymer of -(1→4)-linked N-acetyl galactosaminuronic monomers, with a variable degree of O-acetylation at the C3 position. Vi antigen is a capsular polysaccharide found mainly in Salmonella typhi and Salmonella paratyphi C, two serotypes of Salmonella that are responsible for severe infection in humans.[2] Although in the past years there has been much progress in carbohydrate chemistry, 1,2-cis-selective glycosylation of gluco- or galactosamines is still a challenge. 2-Azidoglycosyl donors, developed many years ago, are still employed for the synthesis of 2-amino-2-deoxy -glycosides, even if glycosylations suffer of low selectivity. Progress in resolving these issues has been made with the development of donors carrying a 2,3-trans-carbamate group, which has attracted much attention as a stereodirecting protection in glycosylation reactions. The fused carbamate ring proved to be a non-participating group and favors the formation of -glycosides. So far, different studies have demonstrated that 2,3-oxazolidinone protected thioglycosides are highly efficient substrates for the synthesis of -linked glycosides.[3] Herein we report a new 2,3-oxazolidinone protected galactosamine donor, bearing an allyl group at the anomeric position. The allyl group, in addition to its traditional role as a valuable anomeric protecting group, can also be converted into a good leaving group for glycosylation. Thus, the allyl glycoside is first isomerized to the corresponding prop-1-enyl glycoside, which, after chemoselective activation of the anomeric enol ether moiety with a suitable electrophile in the presence of the glycosyl acceptor, leads to the formation of the disaccharide product.[4] This method has the advantage that prop-1-enyl glycoside can be directly derived from allyl glycoside with a variety of facile and highly effective isomerization methods and immediately subjected to glycosylation. Herein we describe the synthesis of a galactosamine building block, which has the anomeric position protected by an allyl group, and positions 2 and 3 involved in the formation of an oxazolidinone ring. The proper donor and acceptor to perform a -(1→4) glycosylation have been obtained from this common building block. The new 2,3-oxazolidinone protected allyl galactosamine donor has been subjected to glycosylation reactions to study its reactivity and the stereoselectivity of the process. 1. a) Landersjö, C.; Widmalm, G. Biopolymers 2002, 64,283; b) Takeda, M.; Nakamori, T.; Hatta, M.; Yamada, H.; Koizumi, J.I. Int. J. Biol. Macromol. 2003, 33, 245 2. a) Daniels, E.M.; Schneerson, R.; Egan, W.M.; Szu, S.C.; Robbins, J.B. Infect. Immun. 1989, 57, 31592; b) Heyns, K.; Kiessling, G. Carbohydr. Res. 1967, 3, 340 3. See for examples: a) Kerns R.J., Zha C., Benakli K.,. Liang Y.Z, Tetrahedron Lett. 2003, 44, 8069; b) Olsson, J. D. M.; Eriksson, L.; Lahmann, M.; Oscarson, S. J. Org. Chem: 2008, 73, 7181; c) Yang, L.; Ye, X-S. Carbohydr. Res. 2010, 345, 1713; d) Yang, L.; Zhu, J. ; Zheng, X-J. ; Tai, G. ; Ye, X-S. Chem. Eur. J. 2011, 17, 14518 4. Wang, Y.; Zhang, X.; Wang, P. Org. Biomol. Chem. 2010, 8, 4322 and references herein reported. We acknowledge MIUR-Italy (PRIN 2008) for financial support.