Structural characteristics and properties of substituted cholanoates and N-substituted cholanamides

Abstract

The present thesis reports the synthesis and more detailed structural characterization of some bile acid derivatives based on naturally common cholanoic acids. The structure determination is an important part of efforts to understand the properties and function of these biologically active compounds, which have been of concern to many scientists for decades. This thesis provides new structural information about some derivatives of auxiliary substances of human digestion, namely cholic acid and chenodeoxycholic acid, also called primary bile acids. These primary bile acids are cholesterol metabolites and they can be further transformed to secondary bile acids. In addition to structural data of the derivatives of primary and secondary bile acids, their thermal properties were also examined. A total of five methyl ester (cholanoates), 15 N-hydroxyalkyl amide (cholanamides) and two cyclic cholaphane derivatives of cholanoic acids with their intermediates were prepared. The structures of these compounds were analyzed by powder and single crystal x-ray crystallographic, solid and liquid state NMR, IR as well as mass spectrometric methods. Exact solid state structures of four cholanoates, six cholanamides and two cholanamide solvates were determined by single crystal x-ray crystallography. Thermal analyses included differential scanning calorimetric and thermogravimetric methods. Bile acids are very useful natural tools in organic, bioorganic and supramolecular chemistry. The bile acid nucleus is one of the largest rigid units readily available with enantiomeric purity, unique amphiphilicity and low cost. Cholanoate derivatives are important intermediates in the synthesis of various cholanoic acid derivatives and they can also have utilizable properties themselves, for example in gelation processes or sensing. Cholanamides provide also an attractive backbone for many possible applications, including pharmaceuticals, drug delivery, gelators and other supramolecular systems. Cholaphanes are well-known host molecules in supramolecular chemistry binding various ionic guests, and they can serve as possible model compounds for more complex biological systems.