Preparation of C-glycoside pendant β2- and β2,2-amino acids

Facile preparations of C-glycosyl beta(2)- and beta(2,2)-amino acids are described. Selective formation of a beta-C-glycoside linkage was achieved by the reaction of a 2,3,4,6-tetra-O-acetyl-alpha-D-gluco/galactopyranosyl bromide (alpha-acetobromo-glucose/galactose) with the carbanion of a cyanoacetate ester. Crystallization selectively afforded one of two diastereomers with respect to the chiral center at the alpha-carbon of the side chain (C-2), however, this compound was found to epimerize during the following nitrile reduction. Separation of the diastereomers was achieved via the Fmoc derivatives. Diastereomerically pure C-glycosyl beta(2,2)-amino acids were prepared by diastereoselective alkylation of C-glycosylated enolate, followed by nitrile hydrogenation. The present procedure serves as an efficient route to C-glycosylated beta-amino acids containing a non-biodegradable linkage.