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DOI: 10.1039/A900944B (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1999, 1311-1324

The synthesis of folic acid, multiply labelled with stable isotopes, for bio-availability studies in human nutrition

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Peter Maunder, Paul M. Finglas, Anthony I. Mallet, Fred A. Mellon, M. Aaqib Razzaque, Brian Ridge, Liisa Vahteristo and Cornelia Witthöft

Abstract

Two different methods for the synthesis of folic acid, which are suitable for the incorporation of compounds multiply labelled with stable isotopes, are described. The first method is based on the use of a novel reductive amination to link 2-acetylamino-4-hydroxy-6-formylpteridine with p-aminobenzoyl-L-glutamic acid. The second method is based on the penultimate formation of an amide bond between N-2-acetyl-N-10-trifluoroacetylpteroic acid and dimethyl L-glutamate. Both methods have been used to transform [13C6]aniline into folic acid, labelled with [13C6] in the p-aminobenzoate moiety, and [3,3,4,4-2H4]-L-glutamic acid into folic acid, labelled with [2H4] in the glutamate moiety. Doubly labelled [13C6, 2H4]-p-aminobenzoyl-L-glutamate has also been prepared by the former method.

References

  1. J. M. Scott, D. G. Weir and P. N. Kirke, in Folates in Health and Disease, ed. L. B. Bailey, Marcel Dekker Inc., New York, 1995, p. 329 Search PubMed.
  2. C. J. Boushey, A. A. A. Beresford, G. S. Omenn and A. G. Motulsky, J. Am. Med. Assoc., 1995, 274, 1049 Search PubMed.
  3. J. Mason, in Folates in Health and Disease, ed. L. B. Bailey, Marcel Dekker Inc., New York, 1995, p. 361 Search PubMed.
  4. J. F. Gregory and J. P. Toth, in Folic Acid Metabolism in Health and Disease, Wiley-Liss Inc., 1990, ch. 9, p. 151 and the references contained therein Search PubMed.
  5. (a) C. R. Santhosh-Kumar, J. C. Deutsch, K. L. Hassell, N. M. Kolhouse and J. F. Kolhouse, Anal. Biochem., 1995, 225, 1 CrossRef; (b) M. A. Razzaque, P. M. Finglas, C. Witthöft, B. Ridge, P. Maunder and A. I. Mallet, 22nd Annual Meeting of the British Mass Spectrometry Society, University of Wales, Swansea, September 1996; (c) J. P. Toth and J. F. Gregory, Biomedical and Environmental Mass Spectrometry, 1988, 17, 73 Search PubMed.
  6. J. F. Gregory, S. D. Bhandari, L. B. Bailey, J. P. Toth, T. G. Baumgartner and J. J. Cerda, Am. J. Clin. Nutr., 1991, 53, 736 CAS.
  7. J. F. Gregory, S. D. Bhandari, L. B. Bailey, J. P. Toth, T. G. Baumgartner and J. J. Cerda, Am. J. Clin. Nutr., 1992, 55, 1147 CAS.
  8. C. M. Pfeiffer, L. M. Rogers, L. B. Bailey and J. F. Gregory, Am. J. Clin. Nutr., 1997, 66, 1388 CAS.
  9. L. M. Rogers, C. M. Pfeiffer, L. B. Bailey and J. F. Gregory, J. Nutr., 1997, 127, 2321 CAS.
  10. R. Kalbermatten, W. Städeli, J. H. Bieri and M. Viscontini, Helv. Chim. Acta, 1981, 64, 2627 CAS.
  11. S. R. Ducker, A. D. Jones, G. M. Smith and A. J. Clifford, J. Labelled Compd. Radiopharm., 1995, 36, 981.
  12. J. F. Gregory and J. P. Toth, Anal. Biochem., 1988, 170, 94 CAS.
  13. M. Cowart, C. J. Falzone and S. J. Benkovic, J. Labelled Compd. Radiopharm., 1994, 34, 67 CAS.
  14. L. T. Plante, J. Org. Chem., 1971, 36, 860 CrossRef CAS.
  15. J. H. Bieri and M. Viscontini, Helv. Chim. Acta, 1973, 56, 2905 CAS.
  16. J. I. DeGraw, J. P. Marsh, E. M. Acton, O. P. Crews, C. W. Mosher, A. N. Fujiwara and L. Goodman, J. Org. Chem., 1965, 30, 3404 CAS.
  17. L. T. Plante, K. L. Williamson and E. J. Pastore, Methods Enzymol., 1980, 66, 533 CAS.
  18. P. Maunder, P. M. Finglas, A. I. Mallet, F. A. Mellon, M. A. Razzaque, B. Ridge, L. Vahteristo and C. M. Witthöft, in Chemistry and Biology of Pteridines and Folates, ed. W. Pfleiderer and H. Rokos, Blackwell Wissenschafts-Verlag GmbH, Berlin, Vienna, 1997, p. 77 Search PubMed.
  19. F. Weygand and E. Csendes, Angew. Chem., Int. Ed. Engl., 1952, 64, 136 Search PubMed.
  20. M. Goodman, E. E. Schmidt and D. A. Yphantis, J. Am. Chem. Soc., 1962, 84, 1283 CrossRef CAS.
  21. E. C. Taylor and K. Lenard, Liebigs Ann. Chem., 1969, 726, 100 Search PubMed.
  22. M. Sletzinger, D. Reinhold, J. Grier, M. Beachem and M. Tishler, J. Am. Chem. Soc., 1955, 77, 6365 CrossRef CAS.
  23. E. C. Taylor, R. N. Henrie and R. C. Portnoy, J. Org. Chem., 1978, 43, 736 CrossRef CAS.
  24. H. Gilman and C. G. Stuckwisch, J. Am. Chem. Soc., 1949, 71, 2933 CrossRef CAS.
  25. A. Murray, W. W. Foreman and W. Langham, J. Am. Chem. Soc., 1948, 70, 1037 CrossRef CAS.
  26. B. S. Furniss, A. J. Hannaford, P. W. G. Smith and A. R. Tatchell, Vogel's Textbook of Practical Organic Chemistry, 5th edn., Longman, 1989, p. 909.
  27. E. J. Bourne, S. H. Henry, C. E. M. Tatlow and J. C. Tatlow, J. Chem. Soc., 1952, 4014 RSC.
  28. F. Weygand and E. Leising, Chem. Ber., 1954, 87, 248 CrossRef CAS.
  29. E. E. Schallenberg and M. Calvin, J. Am. Chem. Soc., 1955, 77, 2779 CrossRef CAS.
  30. L. T. Plante, E. J. Crawford and M. Friedkin, J. Biol. Chem., 1967, 242, 1967.
  31. H. A. Godwin, I. H. Rosenberg, C. R. Ferenz, P. M. Jacobs and J. Meienhofer, J. Biol. Chem., 1972, 247, 1972.
  32. S. Werner-Simon and W. Pfleiderer, J. Heterocycl. Chem., 1996, 33, 949 CAS.
  33. F. Weygand, A. Wacker and V. Schmied-Kowarzik, Chem. Ber., 1949, 82, 25 CAS.
  34. H. J. Backer and A. C. Houtman, Recl. Trav. Chim. Pays-Bas, 1951, 70, 738 CAS.
  35. J. Wilbrand and F. Beilstein, Liebigs Ann. Chem., 1904, 128, 265 Search PubMed.
  36. A. P. Melissaris and M. H. Litt, J. Org. Chem., 1994, 59, 5818 CrossRef CAS.
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