Synthesis and Structural Analysis of the Anilides of Glucuronic Acid and Orientation of the Groups on the Carbohydrate Scaffolding

• Published in: Journal of organic chemistry Vol. 70; no. 10; pp. 4096 - 4106
• Main Authors: Tosin, Manuela, O'Brien, Colin, Fitzpatrick, Geraldine M, Müller-Bunz, Helge, Glass, W. Kenneth, Murphy, Paul V
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 13-05-2005
• Subjects: Anilides - chemical synthesis; Anilides - chemistry; Anilides - metabolism; Carbohydrates - chemistry; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Exact sciences and technology; Glucuronic Acid - chemical synthesis; Glucuronic Acid - chemistry; Glucuronic Acid - metabolism; Hydrogen Bonding; Models, Chemical; Organic chemistry; Preparations and properties; Solutions - chemistry; Infrared spectrometry; Glucuronic acid; Configuration; Uronic acid; Oside; NMR spectrometry; Chemical synthesis; Anilide; Structural analysis; Hydrogen bond
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo0501994

The synthesis of anilides derived from glucuronic acid is described. Secondary anilides had a Z configuration in the solid state and showed intramolecular and intermolecular hydrogen bonding. However, on the basis of NMR and IR studies, there was generally no evidence for the same hydrogen bonding in solution. Tertiary anilides showed a strong preference for the E configuration on the basis of NOE studies and molecular mechanics calculations. The alkylation of the secondary anilides induces a configurational switch that alters the orientation of the aromatic group with respect to the pyranose, which has relevance for presentation or orientation of pharmacophoric groups on carbohydrate scaffolds.