[13C,15N]2-acetamido-2-deoxy-D-aldohexoses and their methyl glycosides: Synthesis and NMR investigations of J-couplings involving1H, 13C, and15N

Article abstract of DOI:10.1021/jo051510k

A series of 2-amino-2-deoxy-D-[1-¹³C]aldohexoses and their methyl glycosides was prepared with use of a simplified cyanohydrin reduction route. Four D-aldopentosylamines (arabino, lyxo, ribo, xylo) were prepared from the corresponding D-aldopentoses by reaction with NH₃(g) in MeOH solvent, isolated in solid form, and characterized by ¹³C and ¹H NMR. Hydrolysis of β-D-xylopyranosylamine was studied using ¹³C-labeled substrates to establish optimal solution conditions for cyanohydrin formation. Major hydrolytic intermediates were observed and identified by time-lapse 1D and 2D NMR analyses of reaction mixtures. The aldopentosylamines were subsequently employed in cyanohydrin reduction reactions with K¹³CN to yield C2-epimeric [1-¹³C]2-aminosugars, which were separated by chromatography on ion-exchange columns. N-Acetylation and methyl glycosklation followed by chromatography gave pure 2-acetamido-2-deoxy-D-[1-¹³C]aldohexopyranosicles, J_CH and J_CC spin-spin coupling constants involving the labeled anomeric carbon were measured and compared to those observed previously in methyl D-[1-¹³C]-aldohexopyranosides. In parallel studies, theoretical J-couplings were calculated in model N-acetylated aldopyranosides using density functional theory (DFT) to predict the effect of OH vs NHCOCH₃ substitution at C2 on J_CH and J_CC values in aldopyranosyl rings. The synthetic method was also modified to accommodate ¹⁵N- and ¹³C-labeling within the N-acetyl side-chain, and some J-couplings involving ¹H, ¹³C, and ¹⁵N atoms in 2-[1,2-¹³C₂;¹⁵N]acetamido-2-deoxy-D-[1- ¹³C]glucose were measured and interpreted.