Conformational analysis: ³J_HCOC and ³J_HCCC Karplus relationships for methylene ¹H nuclei

Abstract

NAMFIS (NMR Analysis of Molecular Flexibility In Solution) was applied to 1-[2-(benzyloxy)phenyl]ethanone using quantitative (1)H-(1)H NOE distances and (3)J proton-carbon coupling constant (CC) restraints for averaged methylene proton (3)J(HCOC) and (3)J(HCCC) pathways H2-(3)J-X imposed by density functional theory-generated Karplus relationships. Comparison of the NOE-only versus the NOE + CC conformational selections illustrates that the experimentally measured average (3)J coupling constants of methylene protons can be used for solution conformational analysis, potentially valuable in the study of small-molecule drugs and natural products which lack the typically studied H1-(3)J-X Karplus relationships.