Substituted methyl 5β‐cholan‐24‐oates. I—¹⁷O NMR spectral characterization

Abstract

Methyl esters of four common bile acids, 3a-hydroxy-5gcholan-24-oic (lithocholic) acid, 3a,7a-dihydroxy-5~ cholan-24-oic (chenodeoxycholic) acid, 3a,l2udihydroxy-5~holan-24-oic (deoxycholic) acid and 3a,7a,lZatrihydroxy-5&cholan-24-oic (cholic) acid, and 14 acetylated, trifluoroacetylated, mesylated and 0x0 derivatives of methyl 5gcholan-24-oates were prepared and their "0 NMR spectra recorded. In spite of their relatively high molecular masses and the rigid molecular structure of the steroid skeleton, most of the oxygens included in these structures gave well resolved '"0 NMR resonance lines at natural abundance in 0.25-0.5 M acetonitrile solutions at 75OC. In agreement with the present ''0 NMR results, molecular mechanics calculations revealed that a hydroxy substituent located at the &-position clearly differs from the hydroxyls at the 7a-and 12u-positiom. This is due to the fact that the 3u-hydroxyl possessing only two y-carbons at antiperiplanar positions is less shielded than the other hydroxyls influenced also by the shielding effects of 'y-guuche carbons. The spectral deconvolution of the overlapping signals of the 7a-and 12a-bydroxyls is based on a computer-aided method or on chemical substitutions. The 0x0 groups located at the longitudinal (foxo) vs. transversal (7-and 120x0) axes of the steroid framework show very different quadrupolar relaxation properties and '"0 NMR linewidths owing to the strong anisotropy of overall molecular motion. In contrast, the I7O NMR linewidths of all 3a-, 7a-and 12a-hydroxyls are very similar and clearly smaller than those of the corresponding 0x0 groups, revealing that their quadrupolar relaxation is merely determined by their internal rotation rather than by the overall molecular motion.

Oxygen-17 NMR spectroscopy: Basic principles and applications (Part I)

“…The c-gauche effect was found to be between À7 and À20 ppm. In this connection one should also mention the studies on cholic acid derivatives [396] and steroids selectively enriched up to 45% in 17 O [397]. The spectra of polyhydroxy compounds with overlapping signals were analyzed with a curve-fitting program, which allowed the chemical shifts to be determined with an accuracy of ±0.25 ppm.…”

Bile Acids as Building Blocks of Supramolecular Hosts

“…Publications concerning 15 N- and 17 O-NMR chemical shifts of bile acid-based compounds are very rare. We have presented some 15 N-NMR data of bile acid derivatives [ 85 , 98 , 115 ] and we [ 150 ] and Smith et al . [ 151 ] have collected the 17 O-NMR chemical shifts of some bile acid derivatives and other steroidal compounds.…”

Assignment of the relative configuration of spiro[4.5]decanes by 13C, 15N and 17O NMR

“…rigid molecular framework clearly reflected the molecular environment. 12 In general, an oxygen in the equatorial position showed a broader signal than that in the axial position.…”

“…12 Several investigations have dealt with stereochemical dependences of 17 O chemical shift values of six-membered ring systems derived from alcohols and their corresponding ethers.…”