Crystal structure of chenodeoxycholic acid, ursodeoxycholic acid and their two 3β,7α- and 3β,7β-dihydroxy epimers

The crystal structures of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (7β isomer of CDCA) and their other two epimers (3β,7α- and 3β,7β-isomers) have been resolved. The four isomers were recrystallized from p-xylene. CDCA crystal is hexagonal P65 while the crystals of the other three isomers are orthorhombic (P212121 space group). Only the 3β,7β isomer forms an inclusion complex with the solvent with a 1:1 stoichiometry. In all cases, the three hydrogen bond sites (the two hydroxy groups, O3-H and O7-H, and the carboxylic acid group of the side chain, O24bO24a-H) simultaneously act as hydrogen bond donors and acceptors. By considering that O24a is always donor and O24b is always acceptor, the hydrogen bond sequences can be understood on the basis of the interaction between the two hydroxy groups. However the comparison between the four compounds is complicated by the existence of two molecules in the asymmetric unit in the UDCA crystal resulting in that the same hydrogen bond site (for instance O3) can be donor towards two different acceptors (either O7 or O24b). As in the case of the four isomers of deoxycholic acid (Steroids2004, 69, 379), the other three isomers present a donor → acceptor sequence, which is O7 → O3 when O3–H is β and O3 → O7 when O3-H is α. The spatial orientation of the carboxylic acid of the side chain is referred to two almost perpendicular planes (defined by (1) the carbon atoms C1/C6-C17/C20 and by (2) the methyl groups C18-C19 and the two carbon atoms to which they are linked, C10 and C13, respectively). Only the side chain of CDCA evidences a positive deviation towards the hydrophobic β side of the molecule.