Enzymic synthesis of β-glucuronides of estradiol, ethynylestradiol and other phenolic substrates on a preparative scale employing UDP-glucuronyl transferase

Abstract

By incubation of bovine liver UDP-glucuronyl transferase with various phenolic aglycone substrates, preparation of the corresponding β-glucuronides could be achieved in milligram quantities. Concomitantly, simple access was generated to estrogen steroid glucuronides of great biological importance. In terms of experimental feasibility, direct application of the commercially available crude microsomal product was compared to and proven to be competitive with the usually preferred utilization of an immobilized enzyme preparation.

References

1. D. Zakim, Y. Hochman and D. A. Vessey, Biochemical Pharmacology and Toxicology, ed. D. Zakim and D. A. Vessey, Wiley, New York, 1985, vol. 1, pp. 161–227.
2. C. Fenselau, S. Pallante and I. Parikh, J. Med. Chem., 1976, 19, 679.
3. L. P. Johnson and C. Fenselau, Drug Metab. Dispos., 1978, 6, 677.
4. D. B. Johnson, M. J. Swanson, C. W. Barker, C. B. Fanska and E. E. Murrill, Prep. Biochem., 1979, 9, 391.
5. B. R. Neidlein, M. Wu and H. G. Hege, Arzneim. Forsch./Drug. Res., 1988, 38, 1257.
6. D. Gygax, P. Spies, T. Winkler and U. Pfaar, Tetrahedron, 1991, 47, 5119.
7. S. Oscarson, Top. Curr. Chem., 1997, 186, 171.
8. B. Burchell and P. Weatherill, Methods Enzymol., 1981, 77, 169.
9. K. Kato, K. Yoshida, H. Tsukamoto, M. Nobunaga, T. Masuya and T. Sawada, Chem. Pharm. Bull., 1960, 8, 239.
10. J. S. Elce, J. G. D. Carpenter and A. E. Kellie, J. Chem. Soc. C, 1967, 542.
11. E. D. Helton, M. C. Williams and J. W. Goldzieher, Steroids, 1976, 27, 851.
12. H. E. Hadd, W. Slikker, Jr. and E. D. Helton, J. Steroid Biochem., 1980, 13, 1107.