Bile acid sulfates: II. Synthesis of 3-monosulfates of bile acids and their conjugates (original) (raw)

Abstract

Bile acid 3-monosulfates were synthesized by the sulfation of 3-hydroxy formyloxy bile acids with sulfur trioxide-triethylamine in dimethylformamide at 25 C for 0.5 hr. The protecting formyl groups were then hydrolyzed under mild alkaline conditions, and the deformylated products were isolated as p-toluidinium salts. These p-toluidinium salts were converted easily to the corresponding disodium salts by methanolic sodium hydroxide. Disodium salts were then isolated by precipitation from methanolether. The corresponding glycine conjugates were similarly synthesized by the sulfation of ethyl esters of 3-hydroxy formyloxy bile acid glycine conjugates. However, the taurine-conjugated bile acid sulfates were obtained by conjugating bile acid 3-monosulfates, either as triethylammonium salt or as disodium salt, with taurine in dimethylformamide in the presence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. These procedures produced the desired bile acid sulfates in high yield (typically above 90%) with minimum manipulation. No time-consuming and capacity-limited chromatographic purification was needed to isolate the pure sulfates. The thin layer chromatographic mobilities, the infrared spectra, and some of the preliminary studies of the properties of these synthesized 3-monosulfates are also discussed.

Similar content being viewed by others

Abbreviations

methanol:

absolute methyl alchohol

ether:

absolute diethyl ether

DMF:

dimethylformamide

EEDQ:

N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline

TLC:

thin layer chromatography

IR:

infrared spectrum

3-sulfocholic acid:

3α-sulfooxy-7α,12α-dihydroxy-5β-cholan-24-oic acid

3-sulfoglycocholic acid:

3α-sulfooxy-7α,12α-dihydroxy-5β-cholan-24-oyl-glycine

3-sulfotaurocholic acid:

3α-sulfooxy-7α,12α-dihydroxy-5β-cholan-24-oly-taurine

3-sulfochenodeoxycholic acid:

3α-sulfooxy-7α-hydroxy-5β-cholan-24-oic acid

3-sulfoglycochenodeoxycholic acid:

3α-sulfooxy-7α-hydroxy-5β-cholan-24-oyl-glycine

3-sulfotaurochenodeoxycholic acid:

3α-sulfooxy-7α-hydroxy-5β-cholan-24-oyl-taurine

3-sulfodeoxycholic acid:

3α-sulfooxy-12α-hydroxy-5β-cholan-24-oic acid

3-sulfoglycodeoxycholic acid:

3α-sulfooxy-12α-hydroxy-5β-cholan-24-oyl-glycine

3-sulfotaurodeoxycholic acid:

3α-sulfooxy-12α-hydroxy-5β-cholan-24-oyl-taurine

7-formylchenodeoxycholic acid:

3α-hydroxy-7α-formyloxy-5β-cholan-24-oic acid

12-formyldeoxycholic acid:

3α-hydroxy-12α-formyloxy-5β-cholan-24-oic acid

7,12-diformylcholic acid:

3α-hydroxy-7α,12α-diformyloxy-5β-cholan-24-oic acid

ethyl 7-formylglycochenodeoxycholate:

3α-hydroxy-7α-formyloxy-5β-cholan-24-oyl-glycine ethyl ester

ethyl 12-formylglycodeoxycholate:

3α-hydroxy-12α-formyloxy-5β-cholan-24-oyl-glycine ethyl ester

ethyl 7,12-diformylglycocholate:

3α-hydroxy-7α,-12α-diformyloxy-5β-cholan-24-oylglycine ethyl ester

References

  1. Palmer, R.H., and M.G. Bolt, J. Lipid Res. 12:671 (1971).
    PubMed CAS Google Scholar
  2. Makino, I., K. Shinozaki, S. Nakagawa, and K. Mashimo, J. Lipid Res. 15:132 (1974).
    PubMed CAS Google Scholar
  3. Stiehl, A., Eur. J. Clin. Invest. 4:59 (1974).
    Article PubMed CAS Google Scholar
  4. Makino, I., H. Hashimoto, K. Shinozaki, K. Yoshino, and S. Nakagawa, Gastroenterology 68:545 (1975).
    PubMed CAS Google Scholar
  5. Stiehl, A., D.L. Earnest, and W.H. Admirand, Gastroenterology 68:534 (1975).
    PubMed CAS Google Scholar
  6. Campbell, C.B., C. McGuffie, and L.W. Powell, Clin. Chim. Acta 63:249 (1975).
    Article PubMed CAS Google Scholar
  7. Back, P., J. Sjövall, and K. Sjövall, Med. Biol. 52:31 (1974).
    PubMed CAS Google Scholar
  8. Van Berge Henegouwen, G.P., K.-H. Brandt, H. Eyssen, and G. Parmentier, Gut 17:861 (1976).
    PubMed Google Scholar
  9. Summerfield, J.A., B.H. Billing, and C.H.L. Shackleton, Biochem. J. 154:507 (1976).
    PubMed CAS Google Scholar
  10. Van Berge Hengouwen, G.P., and A.F. Hofmann, Clin. Chim. Acta 73:469 (1976).
    Article Google Scholar
  11. Eyssen, H.J., G.G. Parmentier, and J.A. Mertens, Eur. J. Biochem. 66:507 (1976).
    Article PubMed CAS Google Scholar
  12. Van Berge Henegouwen, G.P., R.N. Allan, A.F. Hofmann, and P.Y.S. Yu, J. Lipid Res. 18:118 (1977).
    PubMed Google Scholar
  13. Simpson, R.M., in “Progress in Hazardous Chemicals Handling and Disposal,” Edited by R.H.L. Hove, Noyes Data Co., Park Ridge, NJ, 1972, pp. 77–102.
    Google Scholar
  14. Matsui, M., M. Hakozaki, and Y. Kinuyama, J. Chromatogr. 115:625 (1975).
    Article PubMed CAS Google Scholar
  15. Balistreri, W.F., A.E. Cowen, A.F. Hofmann, P.A. Szczepanik, and P.D. Klein, Pediatr. Res. 9:757 (1975).
    Article CAS Google Scholar
  16. Mede, K.A., K.Y. Tserng, and P.D. Klein, Gastroenterology 71:921 (1976).
    Google Scholar
  17. Dusza, J.P., J.P. Joseph, and S. Bernstein, Steroids 12:49 (1968).
    Article PubMed CAS Google Scholar
  18. Tserng, K.Y., and P.D. Klein, J. Lipid Res. 18:491 (1977).
    PubMed CAS Google Scholar
  19. Tserng, K.Y., and P.D. Klein, Steroids 29:635 (1977).
    Article PubMed CAS Google Scholar
  20. Parmentier, G., and H. Eyssen, Steroids 26:721 (1975).
    Article PubMed CAS Google Scholar
  21. Cass, O.W., A.E. Cowen, A.F. Hofmann, and S.B. Coffin, J. Lipid Res. 16:159 (1975).
    PubMed CAS Google Scholar
  22. Haselwood, E.S., and G.A.D., Haslewood, Biochem. J. 155:401 (1976).
    Google Scholar
  23. Summerfield, J.A., J.L. Gollan, and B.H. Billing, Biochem. J. 156:339 (1976).
    PubMed CAS Google Scholar
  24. Tserng, K.Y., D.L. Hachey, and P.D. Klein, J. Lipid Res. 18:404 (1977).
    PubMed CAS Google Scholar
  25. Suter, C.M., In “Organic Chemistry of Sulfur,” Wiley, New York, 1944, p. 3.
    Google Scholar
  26. Hirschman, H., and J.S. Williams, J. Biol. Chem. 238:2305 (1963).
    Google Scholar

Download references

Author information

Authors and Affiliations

  1. Division of Biological and Medical Research, Argonne National Laboratory, 60439, Argonne, Illinois
    K. -Y. Tserng & P. D. Klein

Authors

  1. K. -Y. Tserng
  2. P. D. Klein

Additional information

Part I of this series, see reference 18.

About this article

Cite this article

Tserng, K.Y., Klein, P.D. Bile acid sulfates: II. Synthesis of 3-monosulfates of bile acids and their conjugates.Lipids 13, 479–486 (1978). https://doi.org/10.1007/BF02533617

Download citation

Keywords