Synthesis and NMR-characterization of three quinamide-based disaccharide mimetics with unusual cyclohexane twist-conformation

Abstract

The synthesis of amide-linked disaccharide mimetics has been explored starting with carbohydrate-based amines and a protected quinic acid lactone. Benzyl-2-amino-4,6-O-benzylidene-2-deoxy-α/β-D-glucopyranose (12) and D-glucamine (14) were successfully coupled to give the corresponding quinamides (13 and 15), while the quinoylation of O-acetylated L-fucopyranosyl methylamine (7) failed. The latter was prepared from per-O-acetyl-L-fucopyranose via the improved multigram scale synthesis of the corresponding per-O-acetyl-L- fucopyranosyl cyanide (3). Compound 3 was subsequently hydrogenated to yield a mixture of compound 7 and the per-O-acetylated bis-(fucopyranosylmethyl) amine (5). The vicinal coupling constants in the NMR spectra of all quinamide products revealed considerable flexibility of the cyclohexane ring in solution and substantial contributions by twist-chair conformations. ©ARKAT.