Observation of O-H•••N scalar coupling across a hydrogen bond in nocathiacin I

We report here the observation of O-H... N hydrogen-bond (1h)JN,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-N-15 HMBC NMR experiment. The magnitude of the scalar coupling constant 1hJN,OH was accurately measured to be 1.8 +/- 0.1 Hz by a J-resolved H-1-N-15 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 angstrom in all the refined structures, and there are no NOE restraint violations >= 0.23 A. 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. (C) Copyright 2007 John Wiley & Sons, Ltd.