CONFORMATIONAL-ANALYSIS OF BACLOFEN ANALOGS BY H-1 AND C-13 NMR - PHACLOFEN, SACLOFEN, AND HYDROXY-SACLOFEN - INFLUENCE OF THE ANIONIC MOIETY

The conformations of three analogues of baclofen 1: phaclofen, saclofe n, and hydroxy-saclofen 2-4, potent GABAB antagonists, in solution (D2 O) are estimated from high-resolution (300 MHz) H-1 NMR coupling data. Conformations and populations of conformers are calculated by means o f a modified Karplus-like relationship for the vicinal coupling consta nts. 1H NMR spectral analysis evidences how 1-3 keep in;solution the p referred a conformation around C3-C4 bond. A partial rotation is set u p around C2-C3 bond (the conformations about C2-C3 are all highly popu lated in solution) particularly for 2 and 3 while 1 shows a relative p referred a conformation. This evidences the influence of the anionic m oiety.