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DOI: 10.1039/A607850H (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1997, 1353-1356

A new chiral synthesis of bullfrog bile sterol 5β-ranol

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Don W. Harney and Theodore A. Macrides

Abstract

(24R)-27-Nor-5β-cholestane-3α,7α ,12α,24,26-pentol (5β-ranol) has been synthesised by the Wittig olefinic coupling of a steroidal module and a side-chain module followed by reduction and deprotection. The steroidal module is derived from cholic acid by a one-carbon degradation of the side chain to produce norcholic acid followed by the loss of a second carbon in an iododecarboxylation and then synthesis of the triphenylphosphonium iodide. The side-chain module is derived from (S)-(-)-butane-1,2,4-triol by benzylidene protection of the 2,4-diol followed by Swern oxidation to the aldehyde. This general synthetic scheme could be used to produce a range of bile sterols with the (24R)-hydroxy moiety which may have significant hepatoprotective activity against liver damage induced by free radicals or reactive metabolites.

References

  1. T. Kuramoto, Y. Noma and T. Hoshita, Chem. Pharm. Bull., 1983, 31, 1330 CAS.
  2. H. Ishida, S. Kinoshita, R. Natsuyama, H. Nukaya, K. Tsuji, T. Kosuge and Y. Yamaguchi, Chem. Pharm. Bull., 1991, 39, 3153 CAS.
  3. Y. Kosuge, K. Tsuji, H. Ishida and J. M. Broadbent, PCT Int. Appl. WO 88 01,274 (Chem. Abstr., 1989, 110, 88640g) Search PubMed.
  4. P. Fabre, Gaz. Med. Fr., 1989, 36, 79 Search PubMed.
  5. T. A. Macrides, L. M. Naylor, N. Kalafatis, A. Shihata and P. F. A. Wright, Fundam. Appl. Toxicol., 1996, 33, 31 CrossRef CAS.
  6. P. F. A. Wright, L. M. Naylor, N. Kalafatis and T. A. Macrides, presented in part at the 7th International Congress of Toxicology, Seattle, Washington, 1995. ISBN Proceedings, Abstract 7,11.
  7. C. D. Schteingart and A. F. Hofman, J. Lipid Res., 1988, 29, 1387 Search PubMed.
  8. K.-Y. Tserng and P. D. Klein, Steroids, 1976, 29, 635.
  9. R. Monks and I. L. Thomas, J. Labelled Compd. Radiopharm., 1983, 20, 463 CAS.
  10. J. D. White, P. Thermamongkol, C. Kuroda and J. R. Engebrecht, J. Org. Chem., 1988, 53, 5909 CrossRef CAS.
  11. E. L. Eliel, Rec. Chem. Prog., 1961, 22, 129 Search PubMed.
  12. J. F. Normant, A. Alexakis, A. Ghribi and P. Mangeney, Tetrahedron, 1989, 45, 507 CrossRef CAS.
  13. M. Thiam, A. Slassi, F. Chastrette and M. Chastrette, Synth. Commun., 1992, 22, 83 CAS.
  14. F. H. Sangsari, F. Chastrette and M. Chastrette, Synth. Commun., 1988, 18, 1343 CAS.
  15. D. D. Perrin and W. L. F. Amarego, in Purification of Laboratory Chemicals, 3rd edn., Pergamon, Oxford, 1988 Search PubMed.
  16. Washed with aqueous sodium carbonate, dried and vacuum distilled under nitrogen.
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