Total synthesis of phomazarin

Journal of the American Chemical Society

Volumn 121, Issue 11, 1999, Pages 2471-2477

  Boger, Dale L ^a   Hong, Jiyong ^a   Hikota, Masataka ^a   Ishida, Michio ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 TRIAZINE DERIVATIVE; ALKADIENE; ANTHRAQUINONE DERIVATIVE; CARBONYL DERIVATIVE; ETHYLENE DERIVATIVE; HETEROCYCLIC COMPOUND; LITHIUM; PHOMAZARIN; PYRIDINE; REAGENT; TRIETHYL 1,2,4 TRIAZINE 3,5,6 TRICARBOXYLIC ACID; TRIMETHOXYETHYLENE; UNCLASSIFIED DRUG;

ARTICLE; DRUG STRUCTURE; DRUG SYNTHESIS; REACTION ANALYSIS;

EID: 0033599580     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja983631q     Document Type: Article

References (47)

1. Kögl, F.; Sparenburg, J. Recl. Trav. Chim. Pays-Bas 1940, 59, 1180. Kögl, F.; Quackenbush, F. W. Recl. Trav. Chim. Pays-Bas 1944, 63, 251. Kögl, F.; van Wessem, G. C.; Eisbach, O. I. Recl. Trav. Chim. Pays-Bas 1945, 64, 23.
2. Kögl, F.; Sparenburg, J. Recl. Trav. Chim. Pays-Bas 1940, 59, 1180. Kögl, F.; Quackenbush, F. W. Recl. Trav. Chim. Pays-Bas 1944, 63, 251. Kögl, F.; van Wessem, G. C.; Eisbach, O. I. Recl. Trav. Chim. Pays-Bas 1945, 64, 23.
3. Kögl, F.; Sparenburg, J. Recl. Trav. Chim. Pays-Bas 1940, 59, 1180. Kögl, F.; Quackenbush, F. W. Recl. Trav. Chim. Pays-Bas 1944, 63, 251. Kögl, F.; van Wessem, G. C.; Eisbach, O. I. Recl. Trav. Chim. Pays-Bas 1945, 64, 23.
4. Birch, A. J.; Butler, D. N.; Rickards, R. W. Tetrahedron Lett. 1964, 1853.
5. Birch, A. J.; Effenberger, R.; Rickards, R. W.; Simpson, T. J. Tetrahedron Lett. 1976, 27, 2371. Birch, A. J.; Butler, D. N.; Effenberger, R.; Rickards, R. W.; Simpson, T. J. J. Chem. Soc., Perkin Trans. 1 1979, 807.
6. Birch, A. J.; Effenberger, R.; Rickards, R. W.; Simpson, T. J. Tetrahedron Lett. 1976, 27, 2371. Birch, A. J.; Butler, D. N.; Effenberger, R.; Rickards, R. W.; Simpson, T. J. J. Chem. Soc., Perkin Trans. 1 1979, 807.
7. Birch, A. J.; Simpson, T. J. J. Chem. Soc., Perkin Trans. 1 1979, 816.
8. Guay, V.; Brassard, P. J. Heterocycl. Chem. 1987, 24, 1649. Guay, V.; Brassard, P. Synthesis 1987, 294.
9. Guay, V.; Brassard, P. J. Heterocycl. Chem. 1987, 24, 1649. Guay, V.; Brassard, P. Synthesis 1987, 294.
10. Boger, D. L. Chemtracts: Org. Chem. 1996, 9, 149. Boger, D. L. Bull. Chim. Soc., Belg. 1990, 99, 599. Boger, D. L.; Patel, M. In Progress in Heterocyclic Chemistry 1989; Suschitzky, H., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1989; Vol. 1; p 30. Boger, D. L.; Weinreb, S. M. Hetero Diels - Alder Methodology in Organic Synthesis; Academic: San Diego, CA, 1987. Boger, D. L. Chem. Rev. 1986, 86, 781. Boger, D. L. Tetrahedron 1983, 39, 2869.
11. Boger, D. L. Chemtracts: Org. Chem. 1996, 9, 149. Boger, D. L. Bull. Chim. Soc., Belg. 1990, 99, 599. Boger, D. L.; Patel, M. In Progress in Heterocyclic Chemistry 1989; Suschitzky, H., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1989; Vol. 1; p 30. Boger, D. L.; Weinreb, S. M. Hetero Diels - Alder Methodology in Organic Synthesis; Academic: San Diego, CA, 1987. Boger, D. L. Chem. Rev. 1986, 86, 781. Boger, D. L. Tetrahedron 1983, 39, 2869.
12. Boger, D. L. Chemtracts: Org. Chem. 1996, 9, 149. Boger, D. L. Bull. Chim. Soc., Belg. 1990, 99, 599. Boger, D. L.; Patel, M. In Progress in Heterocyclic Chemistry 1989; Suschitzky, H., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1989; Vol. 1; p 30. Boger, D. L.; Weinreb, S. M. Hetero Diels - Alder Methodology in Organic Synthesis; Academic: San Diego, CA, 1987. Boger, D. L. Chem. Rev. 1986, 86, 781. Boger, D. L. Tetrahedron 1983, 39, 2869.
13. Boger, D. L. Chemtracts: Org. Chem. 1996, 9, 149. Boger, D. L. Bull. Chim. Soc., Belg. 1990, 99, 599. Boger, D. L.; Patel, M. In Progress in Heterocyclic Chemistry 1989; Suschitzky, H., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1989; Vol. 1; p 30. Boger, D. L.; Weinreb, S. M. Hetero Diels - Alder Methodology in Organic Synthesis; Academic: San Diego, CA, 1987. Boger, D. L. Chem. Rev. 1986, 86, 781. Boger, D. L. Tetrahedron 1983, 39, 2869.
14. Boger, D. L. Chemtracts: Org. Chem. 1996, 9, 149. Boger, D. L. Bull. Chim. Soc., Belg. 1990, 99, 599. Boger, D. L.; Patel, M. In Progress in Heterocyclic Chemistry 1989; Suschitzky, H., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1989; Vol. 1; p 30. Boger, D. L.; Weinreb, S. M. Hetero Diels - Alder Methodology in Organic Synthesis; Academic: San Diego, CA, 1987. Boger, D. L. Chem. Rev. 1986, 86, 781. Boger, D. L. Tetrahedron 1983, 39, 2869.
15. Boger, D. L. Chemtracts: Org. Chem. 1996, 9, 149. Boger, D. L. Bull. Chim. Soc., Belg. 1990, 99, 599. Boger, D. L.; Patel, M. In Progress in Heterocyclic Chemistry 1989; Suschitzky, H., Scriven, E. F. V., Eds.; Pergamon: Oxford, U.K., 1989; Vol. 1; p 30. Boger, D. L.; Weinreb, S. M. Hetero Diels - Alder Methodology in Organic Synthesis; Academic: San Diego, CA, 1987. Boger, D. L. Chem. Rev. 1986, 86, 781. Boger, D. L. Tetrahedron 1983, 39, 2869.
16. Boger, D. L.; Panek, J. S.; Yasuda, M. Org. Synth. 1987, 66, 142.
17. (a) Dittmar, W.; Sauer, J.; Steigel, A. Tetrahedron Lett. 1969, 5171. Burg, B.; Dittmar, W.; Reim, H.; Steigel, A.; Sauer, J. Tetrahedron Lett. 1975, 2897. Reim, H.; Steigel, A.; Sauer, J. Tetrahedron Lett. 1975, 2901.
18. (a) Dittmar, W.; Sauer, J.; Steigel, A. Tetrahedron Lett. 1969, 5171. Burg, B.; Dittmar, W.; Reim, H.; Steigel, A.; Sauer, J. Tetrahedron Lett. 1975, 2897. Reim, H.; Steigel, A.; Sauer, J. Tetrahedron Lett. 1975, 2901.
19. (a) Dittmar, W.; Sauer, J.; Steigel, A. Tetrahedron Lett. 1969, 5171. Burg, B.; Dittmar, W.; Reim, H.; Steigel, A.; Sauer, J. Tetrahedron Lett. 1975, 2897. Reim, H.; Steigel, A.; Sauer, J. Tetrahedron Lett. 1975, 2901.
20. (b) Neunhoeffer, H.; Fruhauf, H.-W. Liebigs Ann. Chem. 1972, 758, 120. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955. Neunhoeffer, H.; Frey, G. Liebigs Ann. Chem. 1973, 1963. Oeser, E. Liebigs Ann. Chem. 1973, 1970. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955.
21. (b) Neunhoeffer, H.; Fruhauf, H.-W. Liebigs Ann. Chem. 1972, 758, 120. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955. Neunhoeffer, H.; Frey, G. Liebigs Ann. Chem. 1973, 1963. Oeser, E. Liebigs Ann. Chem. 1973, 1970. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955.
22. (b) Neunhoeffer, H.; Fruhauf, H.-W. Liebigs Ann. Chem. 1972, 758, 120. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955. Neunhoeffer, H.; Frey, G. Liebigs Ann. Chem. 1973, 1963. Oeser, E. Liebigs Ann. Chem. 1973, 1970. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955.
23. (b) Neunhoeffer, H.; Fruhauf, H.-W. Liebigs Ann. Chem. 1972, 758, 120. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955. Neunhoeffer, H.; Frey, G. Liebigs Ann. Chem. 1973, 1963. Oeser, E. Liebigs Ann. Chem. 1973, 1970. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955.
24. (b) Neunhoeffer, H.; Fruhauf, H.-W. Liebigs Ann. Chem. 1972, 758, 120. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955. Neunhoeffer, H.; Frey, G. Liebigs Ann. Chem. 1973, 1963. Oeser, E. Liebigs Ann. Chem. 1973, 1970. Neunhoeffer, H.; Werner, G. Liebigs Ann. Chem. 1973, 1955.
25. (c) Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5790. Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5782. Boger, D. L.; Panek, J. S. J. Am. Chem. Soc. 1985, 107, 5745. Boger, D. L.; Panek, J. S. Tetrahedron Lett. 1984, 25, 3175. Boger, D. L.; Panek, J. S. J. Org. Chem. 1982, 47, 3763.
26. (c) Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5790. Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5782. Boger, D. L.; Panek, J. S. J. Am. Chem. Soc. 1985, 107, 5745. Boger, D. L.; Panek, J. S. Tetrahedron Lett. 1984, 25, 3175. Boger, D. L.; Panek, J. S. J. Org. Chem. 1982, 47, 3763.
27. (c) Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5790. Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5782. Boger, D. L.; Panek, J. S. J. Am. Chem. Soc. 1985, 107, 5745. Boger, D. L.; Panek, J. S. Tetrahedron Lett. 1984, 25, 3175. Boger, D. L.; Panek, J. S. J. Org. Chem. 1982, 47, 3763.
28. (c) Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5790. Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5782. Boger, D. L.; Panek, J. S. J. Am. Chem. Soc. 1985, 107, 5745. Boger, D. L.; Panek, J. S. Tetrahedron Lett. 1984, 25, 3175. Boger, D. L.; Panek, J. S. J. Org. Chem. 1982, 47, 3763.
29. (c) Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5790. Boger, D. L.; Duff, S. R.; Panek, J. S.; Yasuda, M. J. Org. Chem. 1985, 50, 5782. Boger, D. L.; Panek, J. S. J. Am. Chem. Soc. 1985, 107, 5745. Boger, D. L.; Panek, J. S. Tetrahedron Lett. 1984, 25, 3175. Boger, D. L.; Panek, J. S. J. Org. Chem. 1982, 47, 3763.
30. Bakker, C. G.; Scheeren, J. W.; Nivard, R. J. F. Recl. Trav. Chim. Pays-Bas 1981, 100, 13. Spinning band distillation required to separate 3 from methyl methoxyacetate and 1,1,1,2-tetramethoxyethane was unnecessary, and material that was as low as 40% 3 worked satisfactorily in the thermal cycloaddition reaction.
31. See also: Boger, D. L.; Mullican, M. D. J. Org. Chem. 1984, 49, 4033. and Boger, D. L.; Brotherton, C. E. J. Org. Chem. 1984, 49, 4050.
32. See also: Boger, D. L.; Mullican, M. D. J. Org. Chem. 1984, 49, 4033. and Boger, D. L.; Brotherton, C. E. J. Org. Chem. 1984, 49, 4050.
33. Kessar, S. V.; Gupta, Y. P.; Mohammad, T.; Goyal, M.; Sawal, K. K. J. Chem. Soc., Chem. Commun. 1983, 400.
34. 3I requires 482.9433).
35. 6, 400 MHz) δ 4.31 (q, 2H, J = 7.2 Hz), 3.97 (s, 3H), 3.90 (s, 3H), 1.28 (t, 3H, J = 7.2 Hz).
36. 2O, 400 MHz) δ 3.88 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H).
37. 3, 376 MHz) δ -7.03 (s).
38. Boger, D. L.; Baldino, C. M. J. Am. Chem. Soc. 1993, 115, 11418.
39. 2CHOH (70%) provided 70:30 and 58:42 mixtures of the corresponding C6:C5 esters (15c,d:16c,d). Details are provided in the Supporting Information.
40. Details of the X-ray structure of 16b are supplied in the Supporting Information and have been deposited with the Cambridge Crystallographic Data Centre.
41. Kenyon, J.; Thaker, K. J. Chem. Soc. 1957, 2531. Chase, B. H.; Hey, D. H. J. Chem. Soc. 1952, 553.
42. Kenyon, J.; Thaker, K. J. Chem. Soc. 1957, 2531. Chase, B. H.; Hey, D. H. J. Chem. Soc. 1952, 553.
43. 6, 400 MHz) δ 7.48 (s, 1H), 7.22 (d, 1H, J = 7.8 Hz), 6.82 (d, 1H, J = 7.8 Hz), 5.01 (s, 1H), 4.18 (s, 3H), 4.00 (s, 3H), 3.93 (s, 3H), 3.89 (s, 3H), 2.73 (t, 2H, J = 7.4 Hz), 1.66 (m, 2H), 1.48 (m, 2H), 1.04 (t, 3H, J = 7.3 Hz).
44. Details are provided in the Supporting Information.
45. Boger, D. L.; Cassidy, K. C.; Nakahara, S. J. Am. Chem. Soc. 1993, 115, 10733.
46. 50 = 8 μg/mL).
47. 8 requires 608). Under the optimized reaction conditions, 31 was not detected.