A Convergent Synthesis of 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid and 5,10-Dideaza-5,6,7,8-tetrahydrohomofolic Acid. An Effective Principle for Carbonyl Group Activation

Journal of Organic Chemistry

Volumn 55, Issue 10, 1990, Pages 3222-3227

  Taylor, Edward C ^a   Harrington, Philip M ^a  

^a PRINCETON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5,6,7,8 TETRAHYDRO 5,10 DIDEAZAHOMOFOLIC ACID; LOMETREXOL; UNCLASSIFIED DRUG;

ARTICLE; DRUG IDENTIFICATION; DRUG SYNTHESIS; MASS SPECTROMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE;

EID: 0025358902     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo00297a044     Document Type: Article

References (26)

1. Beardsley, G. P.; Moroson, B. A.; Taylor, E. C.; Moran, R. G. J. Biol. Chem. 1989. 264. 328.
2. Taylor, E. C.; Wong, G. S. K.; Fletcher, S. R.; Harrington, P. J.; Beardsley, G. P.; Shih, C. J. In Chemistry and Biology of Pteridines; Cooper, B. A., Whitehead, V. M., Eds.; Walter de Gruyter: Berlin, 1986; p 61.
3. Taylor, E. C.; Beardsley, G. P.; Grindey, G. B.; Moran, R. G. In Chemistry and Biology of Pteridines; Cooper, B. A., Whitehead, V. M., Eds.: Walter de Gruyter: Berlin. 1986: p 953.
4. Moran, R. G.; Taylor, E. C.; Beardsley, G. P. Proc. Am. Assoc. Cancer Res. 1985, 26, 231.
5. Beardsley, G. P.; Taylor, E. C.; Shih, C.; Poore, G. A.; Grindey, G. B.; Moran, R. G. Proc. Am. Assoc. Cancer Res. 1986, 27, 259.
6. Moran, R. G.; Taylor, E. C.; Shih, C.; Beardsley, G. P. Proc. Am. Assoc. Cancer Res. 1987, 28, 274.
7. Pizzorno, G.; Moroson, B. A.; Cashmore, A. R.; Taylor, E. C.; Beardsley, G. P. Proc. Am. Assoc. Cancer Res. 1988, 29, 281.
8. Taylor, E. C.; Harrington, P. M.; Warner, J. C. Heterocycles 1988, 27, 1925.
9. Taylor, E. C.; Wong, G. S. K. J. Ore. Chem. 1989 54, 3618.
10. Boschelli, D. H.; Webber, S.; Whiteley, J. M.; Oronsky, A. L.; Kerwar, S. S. Arch. Biochem. Biophys. 1988, 265, 43.
11. Piper, J. R.; McCaleb, G. S.; Montgomery, J. A.; Kisliuk, R. L.; Gaumont, Y.; Thorndike, J.; Sirotnak, F. M. J. Med. Chem. 1988, 31, 2164.
12. Taylor, E. C.; Harrington, P. J.; Fletcher, S. R.; Beardsley, G. P.; Moran, R. G. J. Med. Chem. 1985, 28. 914.
13. The condensation of 6-aminopyrimidines with 1,3-dicarbonyl compounds to give pyrido[2,3-d]pyrimidines is well known: Robins, R. K.; Hitchings, G. H. J. Am. Chem. Soc. 1958, 80, 3449.
14. Bernetti, R.: Mancini, F.; Price, C. C. J. Ore. Chem. 1962. 27. 2863.
15. Sha, C.-K.; Tsou, C.-P. J. Chem. Soc., Chem. Commun. 1986, 310.
16. Sha, C.-K.; Tsou, C.-P.; Li, Y.-C.; Lee, R.-S.; Tsai, F.-Y.; Yeh, R.-H. J. Chem. Soc., Chem. Commun. 1988, 1081.
17. DeGraw, J. I.; Tagawa, H.; Christie, P. H.; Lawson, J. A.; Brown, E. G.; Kisliuk, R. L.; Gaumont, Y. J. Heterocycl. Chem. 1986, 23, 1.
18. An alternative synthesis of the closely related enamine has been achieved (ref 16) in low yield by condensation of the enamine derived from 11a (itself prepared in low yield from p-toluic acid) with (ethoxymethylene) malononitrile; this compound was subsequently utilized for the synthesis of a 2-amino-3-cyanopyridine derivative by reaction with ammonia (cf. 5 to 6).
19. Taylor, E. C.; Sowinski, F. J. Ore. Chem. 1974, 39, 907.
20. The initial condensation of 1,3-dicarbonyl compounds with 6-aminopyrimidines also takes place at the 5-position: see ref 13a.
21. Taylor, E. C.; Ray, P. S. J. Ore. Chem. 1987, 52, 3997.
22. Taylor, E. C.; Ray, P. S. J. Org. Chem. 1988, 53. 35.
23. Taylor, E. C.; Yoon, C.-M. Synth. Commun. 1988, 18, 1187.
24. Dictionary of Organic Compounds, Oxford University Press: New York, 1965.
25. Neither satisfactory elemental analyses nor a high resolution mass spectrum could be obtained for this compound, since it underwent extensive decomposition upon standing. However, the identity of 12 was fully confirmed by its conversion to 13, which was fully characterized.
26. Baldwin, J. J.; Raab, A. W.; Ponticello, G. S. J. Org. Chem. 1978, 43, 2529.