Investigations towards the Synthesis of 5-Amino-l-lyxofuranosides and 4-Amino-lyxopyranosides and NMR Analysis

Abstract

The reactivity of trifluoromethanesulfonyl esters derived from L-lyxofuranosides and L-lyxopyranosides was investigated with various 5-aminopyrimidines as nucleophiles with the expectation to synthesize N-substituted 5-amino-ribosugars. The lyxopyranoside forms were found to be unreactive, while the lyxofuranoside forms were found to be reactive with 5-aminopyrimidines, yielding novel N-substituted 5-amino-lyxofuranosides. We report on the synthesis of these novel N-substituted lyxofuranosides and the systematic analyses of NMR data that demonstrate trends within each series: furano-, pyrano-, β-and α-anomers of L-lyxose and β-D-ribopyranoside forms. The data call for caution when identifying these monosaccharides in isomeric mixtures. Key words L-lyxofuranoses, L-lyxopyranoses, D-ribopyranoses, conformation analysis, heterocycles, NMR spectroscopyIn our research exploring the self-assembly properties of alternative recognition elements such as 5-aminouracil and 2,4,5-triaminopyrimidine substituted-pyrrolidines, it was necessary to develop new N-substituted 4-amino-D-ribofuranose sugars. [1][2][3] We proposed the corresponding Llyxopyranose derivatives as outlined in Scheme 1 as intermediates en route to the final pyrrolidine compounds. This synthetic approach is based on the fact that nucleophiles can attack the C(4) position of a substituted lyxopyranose sugar (with a good leaving group at the C(4)-position) through a bimolecular nucleophilic substitution (S N 2) displacement, resulting in the corresponding ribopyranose framework. [4][5][6][7] However, the synthesis of N-substituted 4-amino-D-ribopyranose derivatives proved problematic with amino pyrimidine heterocycles, presumably due to the poor nucleophilicity of these alternative amino nucleobases. For comparison, we also studied the S N 2 reaction with the L-lyxofuranosyl series with the awareness that 5-amino-heterocycles may react more readily at a primary carbon. When comparing the results of the L-lyxopyranose and L-lyxofuranose series, we found that there could be some uncertainty in the assignments as α/β anomeric mixtures of alcohols derived from L-lyxose when they are actually furanoside/pyranoside mixtures. 8 To clarify this issue, we have synthesized, measured NMR spectra and contrasted the chemical shift trends of the furanosyl and pyranosyl Llyxose series -both from this work and those in the literature -and came to the conclusion that identifying the minor compound in isomeric mixtures of monosaccharides can be crucial and should always rely on accurate identification based on corroborating NMR techniques.