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

Chemistry and Physics of Lipids
Shoujiro OgawaT Iida

Abstract

The (25R)- and (25S)-epimers of C(27) 3α,7α,12α-trihydroxy-5α-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 NaBH(4)/triethylamine/ethyl chloroformate, (2) iodination of the resulting 3,7,12-triformyloxy-5α-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)-3α,7α,12α-trihydroxy-5α-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 3α,7α,12α-trihydroxy-5α-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 (1)H and (13)C NMR. These...Continue Reading

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Citations

Aug 6, 2013·European Journal of Medicinal Chemistry·T Vijai Kumar ReddyC Ganesh Kumar
Nov 13, 2014·Organic & Biomolecular Chemistry·Yu V ErmolovichV A Khripach

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