Synthesis and mutagenicity of a ring-A-aromatized bile acid, 3-hydroxy-19-nor-1,3,5(10)-cholatrien-24-oic acid.
It has been presumed that ring-A-aromatized bile acids are produced from biliary bile acids by intestinal flora and the acids thus formed participate in the large bowel carcinogenesis. One of these acids is probably 3-hydroxy-19-nor-1,3,5(10)-cholatrien-24-oic acid, judged from the literatures. Consequently, this acid was synthesized from previously prepared 3-methoxy-19-nor-1,3,5(10)-cholatrien-24-ol. The phenolic ether was successively oxidized with pyridinium chlorochromate and wet silver oxide to give 3-methoxy-19-nor-1,3,5(10)-cholatrien-24-oic acid in high yield, which, after successive treatments with methanol containing a catalytic amount of p-toluenesulfonic acid, a combination of aluminum chloride and ethanethiol, and alkali, gave the desired compound in satisfactory yield. The compound was not mutagenic in Salmonella tester strains TA 98 and TA 100, but it increased the mutagenicity of 2-aminoanthracene when both were applied to plates together. When compared with cholic, deoxycholic, and lithocholic acids, the investigated compound exhibited about two to threefold increase of mutagenicity in the latter assay.
Namba
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T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Hirota
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T
Hayakawa
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S
D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000633:toxicity; D002770:Cholenes / Q000138:chemical synthesis* / Q000633:toxicity; D009152:Mutagenicity Tests; D009153:Mutagens / Q000138:chemical synthesis*; D009654:Norsteroids / Q000138:chemical synthesis / Q000633:toxicity; D012475:Salmonella / Q000187:drug effects / Q000235:genetics
D001647:Bile Acids and Salts; D002770:Cholenes; D009153:Mutagens; D009654:Norsteroids; C057440:3-hydroxy-19-nor-1,3,5(10)-cholatrien-24-oic acid