4.3 Article

Chemical synthesis of the (25R)- and (25S)-epimers of 3α,7α,12α-trihydroxy-5α-cholestan-27-oic acid as well as their corresponding glycine and taurine conjugates

期刊

CHEMISTRY AND PHYSICS OF LIPIDS
卷 164, 期 5, 页码 368-377

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.chemphyslip.2011.04.008

关键词

Allo-bile acid; 5 alpha-Bile acid; 3 alpha,7 alpha,12 alpha-Trihydroxy-5 alpha-cholestan-27-oic acid; Bile acid biosynthesis; Chemical synthesis; NMR

资金

  1. Ministry of Education, Culture, Sports, Science and Technology of Japan [21550091]
  2. MEXT [S0901022]
  3. National Institutes of Health [K08-GM074238]
  4. Grants-in-Aid for Scientific Research [23590209, 21590184, 21550091] Funding Source: KAKEN

向作者/读者索取更多资源

The (25R)- and (25S)-epimers of C-27 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-cholestan-27-oic acid as well as their corresponding N-acylamidate conjugates with glycine or taurine were prepared starting from cholic acid in 14 steps. The principal reactions involved were (1) reduction of a key intermediary C-24 allo-cholic acid performate with NaBH4/triethylamine/ethyl chloroformate, (2) iodination of the resulting 3,7,12-triformyloxy-5 alpha-cholan-24-ol with I-2/triphenylphosphine; (3) nucleophilic substitution of the iodo derivative with diethylmethyl malonate/NaH; and (4) hydrolysis of the resulting 3,7,12-triformyloxy-25-methyl-26,27-diethyl ester with KOH, followed by decarboxylation of the geminal dicarboxylic acid with LiCl. N-Acylamidation of the resulting (25R)/(25S)-3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-cholestan-27-oic acid mixture with glycine or taurine afforded the corresponding epimeric mixtures of the glycine and taurine conjugates. The (25R)- and (25S)-epimers of the three variants of unconjugated and conjugated 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-cholestan-27-oic acid were efficiently separated by HPLC on a reversed-phase C-18 column and their structural characteristics, particularly the chiral center at C-25, delineated using I H and C-13 NMR. These synthetic compounds should be useful as authentic reference standards for establishing their presence in bile as well as being useful in studies on the biosynthesis of alto-bile acids from cholesterol. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

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