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

Abstract

Single crystal X-ray structures (monoclinic space group P2 1 ) for methyl 3-oxo-5β-cholan-24-oate and methyl 3,12-dioxo-5β-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 3α-hydroxy-5β-cholan-24-oate. Probable reasons for the observed differences are discussed. In addition, 13C and 17O NMR chemical shifts of methyl 3-oxo-5β-cholan-24-oate and methyl 3,12-dioxo-5β-cholan-24-oate as well as the epimeric methyl 3α-hydroxy-5β-cholan-24-oate and methyl 3β-hydroxy-5β-cholan-24-oate have been calculated (DFT/B3LYP/6-311G*) and compared with the experimental values by linear regression analyses. In general, the correspondence between the theoretical and experimental parameters is good or excellent.