Comparison of calculated DFT/B3LYP and experimental 13C and 17O NMR chemical shifts, ab initio HF/6-31G* optimised structures, and single crystal X-ray structures of some substituted methyl 5β-cholan-24-oates

Single crystal X-ray structures (monochnic space group P2(1)) for methyl 3-oxo-5beta-cholan-24-oate and methyl 3,12-dioxo-5beta-cholan-24-oate have been solved and compared with HF/6-31G* optimised structures. In the crystalline packings the side chains are connected with weak OC(sp(3))H...O-type of interactions between C25-H and C24-O-C25 and the keto ends with weak C(sp(3))H...O=C-type of interactions between C4-H and O=C3. The orientations of the side chains, which steric configurations are of great importance to the biological activity of the molecules, are compared with the experimental structure of methyl 3alpha-hydroxy-5beta-cholan-24-oate. Probable reasons for the observed differences are discussed. In addition, C-13 and O-17 NMR chemical shifts of methyl 3-oxo-5beta-cholan-24-oate and methyl 3,12-dioxo-5p-cholan-24-oate as well as the epimeric methyl 3alpha-hydroxy-5beta-cholan-24-oate and methyl 3beta-hydroxy-5beta-cholan-24-oate have been calculated (DFT/B3LYP/6311 G*) and compared with the experimental values by linear regression analyses. In general, the correspondence between the theoretical and experimental parameters is good or excellent. (C) 2003 Elsevier Science B.V. All rights reserved.