Vinyl and alkynyl pyrimidines as Michael acceptors: An approach to a cylindrospermopsin substructure

Journal of Organic Chemistry

Volumn 65, Issue 18, 2000, Pages 5668-5675

  Djung, Jane F ^a   Hart, David J ^a   Young, Erick R R ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKYNYL GROUP; CARBAMIC ACID; DIMETHYLDIOXIRANE; GUANIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; REAGENT; UREA; VINYL DERIVATIVE;

ARTICLE; CHEMICAL STRUCTURE; HYDROXYLATION; OXIDATION; REACTION ANALYSIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS; SYNTHESIS;

MAGNETIC RESONANCE SPECTROSCOPY; SPECTROPHOTOMETRY, INFRARED; URACIL;

EID: 0033832952     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo000504f     Document Type: Article

References (46)

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16. Snider, B. B.; Harvey, T. C. Tetrahedron Lett. 1995, 36, 4587. Snider, B. B.; Xie, C. Tetrahedron Lett. 1998, 39, 7021. The first total synthesis of cylindrospermposin was reported while this submission was undergoing review: Xie, C.; Runnegar, M. T. C.; Snider, B. B. J. Am. Chem. Soc. 2000, 122, 5017. In addition model studies were reported by two other groups: McAlpine, I. J.; Armstrong, R. W. Tetrahedron Lett. 2000, 41, 1849. White, J. E.; Hansen, J. D. Book of Abstracts, 219th National Meeting of the American Chemical Society, San Francisco, CA, March 26-30, 2000; American Chemical Society: Washington, DC, 2000.
17. Snider, B. B.; Harvey, T. C. Tetrahedron Lett. 1995, 36, 4587. Snider, B. B.; Xie, C. Tetrahedron Lett. 1998, 39, 7021. The first total synthesis of cylindrospermposin was reported while this submission was undergoing review: Xie, C.; Runnegar, M. T. C.; Snider, B. B. J. Am. Chem. Soc. 2000, 122, 5017. In addition model studies were reported by two other groups: McAlpine, I. J.; Armstrong, R. W. Tetrahedron Lett. 2000, 41, 1849. White, J. E.; Hansen, J. D. Book of Abstracts, 219th National Meeting of the American Chemical Society, San Francisco, CA, March 26-30, 2000; American Chemical Society: Washington, DC, 2000.
18. Snider, B. B.; Harvey, T. C. Tetrahedron Lett. 1995, 36, 4587. Snider, B. B.; Xie, C. Tetrahedron Lett. 1998, 39, 7021. The first total synthesis of cylindrospermposin was reported while this submission was undergoing review: Xie, C.; Runnegar, M. T. C.; Snider, B. B. J. Am. Chem. Soc. 2000, 122, 5017. In addition model studies were reported by two other groups: McAlpine, I. J.; Armstrong, R. W. Tetrahedron Lett. 2000, 41, 1849. White, J. E.; Hansen, J. D. Book of Abstracts, 219th National Meeting of the American Chemical Society, San Francisco, CA, March 26-30, 2000; American Chemical Society: Washington, DC, 2000.
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22. This plan was patterned after the well-known ability of vinyl pyridines to behave as Michael acceptors. For references of some relevance, see: Gray, A. P.; Platz, R. D.; Chang, T. C. P.; Leverone, T. R.; Ferrick, D. A.; Kramer, D. N. J. Med. Chem. 1985, 28, 111 (vinyl pyridines). Macor, J. E.; Ordway, T.; Smith, R. L.; Verhoest, P. R.; Mack, R. A. J. Org. Chem. 1996, 61, 3228 (5-vinyl-1,2,4-oxadiazoles). Schroeder, A. C.; Bloch, A.; Perman, J. L.; Bobek, M. J. Med. Chem. 1982, 25, 1255 (6-ethynyluracils). For other chemistry of some relevance to this research, see: Jacobi, P. A.; Liu, H. J. Am. Chem. Soc. 1999, 121, 1958.
23. This plan was patterned after the well-known ability of vinyl pyridines to behave as Michael acceptors. For references of some relevance, see: Gray, A. P.; Platz, R. D.; Chang, T. C. P.; Leverone, T. R.; Ferrick, D. A.; Kramer, D. N. J. Med. Chem. 1985, 28, 111 (vinyl pyridines). Macor, J. E.; Ordway, T.; Smith, R. L.; Verhoest, P. R.; Mack, R. A. J. Org. Chem. 1996, 61, 3228 (5-vinyl-1,2,4-oxadiazoles). Schroeder, A. C.; Bloch, A.; Perman, J. L.; Bobek, M. J. Med. Chem. 1982, 25, 1255 (6-ethynyluracils). For other chemistry of some relevance to this research, see: Jacobi, P. A.; Liu, H. J. Am. Chem. Soc. 1999, 121, 1958.
24. This plan was patterned after the well-known ability of vinyl pyridines to behave as Michael acceptors. For references of some relevance, see: Gray, A. P.; Platz, R. D.; Chang, T. C. P.; Leverone, T. R.; Ferrick, D. A.; Kramer, D. N. J. Med. Chem. 1985, 28, 111 (vinyl pyridines). Macor, J. E.; Ordway, T.; Smith, R. L.; Verhoest, P. R.; Mack, R. A. J. Org. Chem. 1996, 61, 3228 (5-vinyl-1,2,4-oxadiazoles). Schroeder, A. C.; Bloch, A.; Perman, J. L.; Bobek, M. J. Med. Chem. 1982, 25, 1255 (6-ethynyluracils). For other chemistry of some relevance to this research, see: Jacobi, P. A.; Liu, H. J. Am. Chem. Soc. 1999, 121, 1958.
25. This plan was patterned after the well-known ability of vinyl pyridines to behave as Michael acceptors. For references of some relevance, see: Gray, A. P.; Platz, R. D.; Chang, T. C. P.; Leverone, T. R.; Ferrick, D. A.; Kramer, D. N. J. Med. Chem. 1985, 28, 111 (vinyl pyridines). Macor, J. E.; Ordway, T.; Smith, R. L.; Verhoest, P. R.; Mack, R. A. J. Org. Chem. 1996, 61, 3228 (5-vinyl-1,2,4-oxadiazoles). Schroeder, A. C.; Bloch, A.; Perman, J. L.; Bobek, M. J. Med. Chem. 1982, 25, 1255 (6-ethynyluracils). For other chemistry of some relevance to this research, see: Jacobi, P. A.; Liu, H. J. Am. Chem. Soc. 1999, 121, 1958.
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27. The required alkyne was prepared in 81% yield by reaction of 1,2-epoxyhexane with lithium acetylide ethylenediamine complex in DMSO at room temperature (see Experimental Section).
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30. 10.
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33. It is notable that similar treatment of 10b gave only a 15% yield of the corresponding alcohol. It was suspected that metalation of the benzyl groups might have been problematic with this substrate.
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35. Mook, R. Jr.; Sher, P. M. Org. Synth. 1988, 66, 75.
36. 9 (δ 3.13).
37. It is notable that a carbamate related to 8 (replace OMe with OBn) gave largely the conjugated enyne resulting from elimination upon treatment with NaH in THF (67% yield).
38. Whereas the oxidation of 27 failed, the hydroxylation of 4-alkyl-2,6-dimethoxypyrimidines with 2-phenylsulfonyl-3-phenyloxaziridine reagent may have some generality. For example, in one experiment, deprotonation of 4-methyl-2,6-dimethoxypyrimidine with n-butyllithium followed by reaction with the oxaziridine gave equal amounts of 4-hydroxymethyl-2,6-dimethoxypyrimidine and the product derived from addition of the initially formed anion to N-phenylsulfonylbenzaldimine generated during the course of the hydroxylation reaction.
39. 9.
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42. 1H NMR spectrum of the mixture.
43. All of the chemistry described for 25 has also been accomplished with 26. Details will appear in the Ph.D. Thesis of J.F.D.
44. The separation-inversion protocol provides a 55% yield of 30 starting from a 78:22 mixture of 29 and 30. (
45. General procedures can be found at the beginning of the Experimental Section of: Atarashi, S.; Choi, J.-K.; Ha, D.-C.; Hart, D. J.; Kuzmich, C.; Lee, C.-S.; Ramesh, S.; Wu, S. C. J. Am. Chem. Soc. 1997, 119, 6226.
46. Available from a commercial source.