Conformational distribution of baclofen analogues by ¹H and ¹³C NMR analysis and ab initio HF MO STO-3G or STO-3G* calculations

The conformations of 3-(substituted furan-2-yl) and 3-(substituted thien-2-yl)-γ-aminobutyric acid 1-9 in solution (D₂O) are estimated from high-resolution (300 MHz) ¹H NMR coupling data. Conformations and populations of conformers are calculated by means of a modified Karplus-like relationship for the vicinal coupling constants. The results are compared with X-ray crystallographic investigations (torsion angles) and ab initio HF MO ST-3G or STO-3G* calculations. ¹H NMR spectral analysis shows how 1-9 in solution retain the preferred g^- conformation around the C3C4 bond, as found in the solid state, while a partial rotation is set up around the C2C3 bond: the conformations about C2C3 are all highly populated in solution. The ¹³C spin-lattice relaxation times are also discussed. © 1993.