Characterization of the Two Fundamental Conformations of Benzoylureas and Elucidation of the Factors That Facilitate Their Conformational Interchange

Author(s): Lessene, G; Smith, BJ; Gable, RW; Baell, JB;
Details: Publication Year 2009-09-04,Volume 74,Issue #17,Page 6511-6525
Journal Title: JOURNAL OF ORGANIC CHEMISTRY
Publication Type: Journal Article
Abstract: The ability of the benzoylurea core to mimic alpha helices relies on its ability to form an intramolecular hydrogen bond. The conformational behavior of benzoylureas is investigated in depth in this study via the use of NMR, IR, X-ray, and computational analysis. The results show that the closed conformation maintained by an intramolecular hydrogen bond is favored in most of the cases studied except when steric and electronic effects combined with a solvent possessing a high hydrogen bond accepting ability, such as DMSO, are involved. The study highlights the propensity for benzoylureas to switch conformation depending on the environment of the molecule for a particular set of substituents. We anticipate that our summary of the phenomenon of internal hydrogen bonding and its analysis may further serve as a useful reference source for future workers in this area.
Publisher: AMER CHEMICAL SOC
Keywords: TEMPERATURE-DEPENDENT CHANGES; HYDROGEN-BONDING PHENOMENA; NH CHEMICAL-SHIFTS; BCL-X-L; ALPHA-HELIX; NONPEPTIDE MIMETICS; MOLECULAR SCAFFOLDS; MAGNETIC-RESONANCE; FOLDING PATTERN; CONOTOXIN GVIA
Publisher's Version: https://doi.org/10.1021/jo900871a
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2009-09-04 12:00:00