Bile acids with a cyclopropyl-containing side chain. 3. 1 separation, identification, and properties of all four stereoisomers of 3α,7β-dihydroxy-22,23-methylene-5β-cholan-24-oic acid

3α,7β-Dihydroxy-22,23-methylene-5β-cholan-24-oic acid (CUDCA) (2a), a side-chain cyclopropylog of ursodeoxycholic acid (UDCA) (1), was shown to be a mixture of four stereoisomers (CUDCA A-D). The 22S,23S (3), 22R,23R (4), 22S,23R (5), and 22R,23S (6) diastereoisomers have been separated, their respective configurations assigned by ¹³C NMR spectroscopy, and original synthetic schemes for their preparation elaborated. Moreover, theoretical models of the structure of UDCA and CUDCA A-D were built by using molecular computer graphic techniques. It was shown that the four diastereoisomers (3-6) greatly differ in hydrophilicity, in critical micellar concentration (CMC) in water, and exhibit a different interaction with intestinal bacterial enzymes. It was also shown that CUDCA A-C are not conjugated with glycine or taurine in the liver, while CUDCA D is secreted into bile predominantly as taurine and glycine conjugate.