SUBSTITUTED METHYL 5-BETA-CHOLAN-24-OATES .1. O-17 NMR SPECTRAL CHARACTERIZATION

Methyl esters of tour common bile acids, 3 alpha-hydroxy-5 beta-cholan -24-oic (lithocholic) acid, 3 alpha,7 alpha-dihydroxy-5 beta-cholan-24 -oic (chenodeoxycholic) acid, 3 alpha,12 alpha-dihydroxy-5 beta-cholan -24-oic (deoxycholic) acid and 3 alpha,7 alpha,12 alpha-trihydroxy-5 b eta-cholan-24-oic (cholic) acid, and 14 acetylated, trifluoroacetylate d, mesylated and ore derivatives of methyl 5 beta-cholan-24-oates were prepared and their O-17 NMR spectra recorded. In spite of their relat ively high molecular masses and the rigid molecular structure of the s teroid skeleton, most of the oxygens included in these structures gave well resolved O-17 NMR resonance lines at natural abundance in 0.25-0 .5 M acetonitrile solutions at 75 degrees C. In agreement with the pre sent O-17 NMR results, molecular mechanics calculations revealed that a hydroxy substituent located at the 3 alpha-position clearly differs from the hydroxyls at the 7 alpha- and 12 alpha-positions. This is due to the fact that the 3 alpha-hydroxyl possessing only two gamma-carbo ns at antiperiplanar positions is less shielded than the other hydroxy ls influenced also by the shielding effects of gamma-gauche carbons. T he spectral deconvolution of the overlapping signals of the 7 alpha- a nd 12 alpha-hydroxyls is based on a computer-aided method or on chemic al substitutions. The oxo groups located at the longitudinal (fore) vs . transversal (7- and 12-oxo) axes of the steroid framework show very different quadrupolar relaxation properties and O-17 NMR linewidths ow ing to the strong anisotropy of overall molecular motion. In contrast, the O-17 NMR linewidths of all 3 alpha-, 7 alpha- and 12 alpha-hydrox yls are very similar and clearly smaller than those of the correspondi ng oxo groups, revealing that their quadrupolar relaxation is merely d etermined by their internal rotation rather than by the overall molecu lar motion.