TY - JOUR
T1 - 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
AU - Pellicciari, Roberto
AU - Natalini, Benedetto
AU - Cecchetti, Sergio
AU - Porter, Barry
AU - Roda, Aldo
AU - Grigolo, Brunella
AU - Balducci, Renzo
PY - 1988
Y1 - 1988
N2 - 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.
AB - 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.
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M3 - Article
C2 - 3351848
AN - SCOPUS:0023885192
VL - 31
SP - 730
EP - 736
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 4
ER -