Bile acids with a cyclopropyl-containing side chain. 3. Separation, identification, and properties of all four stereoisomers of 3 alpha,7 beta-dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid.
3 alpha,7 beta-Dihydroxy-22,23-methylene-5 beta-cholan-24-oic acid (CUDCA) (2a), a side-chain cyclopropylog of ursodeoxycholic acid (UDCA) was shown to be a mixture of four stereoisomers (CUDCA A-D). The 22S,23R, and 22R,23S 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 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.
Pellicciari
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R
Istituto di Chimica Farmaceutica e Tecnica Farmaceutica, Università degli Studi, Perugia, Italy.
Natalini
B
B
Cecchetti
S
S
Porter
B
B
Roda
A
A
Grigolo
B
B
Balducci
R
R
D000818:Animals; D001647:Bile Acids and Salts / Q000302:isolation & purification*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003198:Computer Simulation; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D014580:Ursodeoxycholic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000378:metabolism
D001647:Bile Acids and Salts; D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid; C041489:3,7-dihydroxy-22,23-methylenecholan-24-oic acid