Synthesis of Lego bricks: sugar amino acids as foldameric building blocks

Preparations of β-sugar amino acids as H-RibAFU(ip)-OH, (-tX-) and its C-3 epimer, H-XylAFU(ip)-OH, (-cX-) were investigated with the purpose of finding an efficient and economical synthetic pathway in multigram scale and high yield.

To synthesize foldameric intermediate products H-tX-OH and H-cX-OH starting from D-glucose, alternative routes with different sulfonate esters and various reaction conditions were studied. The sulfonate→azide replacement was conducted by using various 3-O-sulfonyl derivatives, such as the triflate, the mesylate, the tosylate, and the imidazylate to get optimized conditions. The carboxyl function was evolved with a two-step oxidation via transformation of aldehyde compounds.

To prepare β-dipeptides, coupling trans AFU derivatives, N-methylated 3-amino-3-deoxy-ribofuranuronamide with the related 3-azido-3-deoxy-ribofuranuronic acid, were carried out in solution under the usual conditions of peptide bond formation to form type N3-tX-tX-NHMe.