Observation of OH…N scalar coupling across a hydrogen bond in nocathiacin I

✍ Scribed by Xiaohua Stella Huang; Xiaohong Liu; Keith L. Constantine; John E. Leet; Vikram Roongta

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 337 KB
• Volume: 45
• Category: Article
• ISSN: 0749-1581
• DOI: 10.1002/mrc.1986

✦ Synopsis

Abstract

We report here the observation of __O__H…N hydrogen‐bond ^1h^J~N, OH~ scalar coupling in a biologically active natural product. The intramolecular hydrogen bond between the threonine hydroxyl (Thr‐OH) group and the thiazolyl nitrogen at the second thiazole ring (Thz‐2) in nocathiacin I was directly detected by a ^1^H^15^N HMBC NMR experiment. The magnitude of the scalar coupling constant ^1h^J~N, OH~ was accurately measured to be 1.8 ± 0.1 Hz by a J‐resolved ^1^H^15^N HMBC experiment. By adding the __O__H…N distance restraint, the 3D solution structure of nocathiacin I was refined. The structure refinement indicated that the distance between the Thr‐3 hydroxyl hydrogen and the Thz‐2 nitrogen is ⩽2.50 Å in all the refined structures, and there are no NOE restraint violations ≥ 0.23 Å. The presence of an intramolecular hydrogen bond in nocathiacin I is further supported by a number of NMR parameters and additional NMR experiments. This observation provides valuable information for characterizing molecular conformations, and for studying structure‐activity relationships. Copyright © 2007 John Wiley & Sons, Ltd.