Synthesis of podophyllotoxin A-ring pyridazine analogue

Tetrahedron

Volumn 52, Issue 45, 1996, Pages 14235-14246

  Bertounesque, Emmanuel ^a   Imbert, Thierry ^b   Monneret, Claude ^a  

^a INSTITUT CURIE   (France)

^b INSTITUT DE RECHERCHE PIERRE FABRE   (France)

Author keywords

[No Author keywords available]

Indexed keywords

PODOPHYLLOTOXIN;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 16044363432     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4020(96)00862-9     Document Type: Article

References (106)

1. 1. Hartwell, J.L.; Schrecker, A.W., Fortschr. Chem. Org. Naturst. 1958, 15, 83.
2. 2. Hartwell, J.L.; Schrecker, A.W. J. Am. Chem. Soc. 1951, 73, 2909.
3. 3. King, L.S.; Sullivan, M.S. Science, 1946, 104, 244. Jardine, I. In Anticancer Agents Based on Natural Product Models, Cassady, J.M.; Douros, J.D., Eds.; Academic Press : New York, 1980, pp. 319-351.
4. 3. King, L.S.; Sullivan, M.S. Science, 1946, 104, 244. Jardine, I. In Anticancer Agents Based on Natural Product Models, Cassady, J.M.; Douros, J.D., Eds.; Academic Press : New York, 1980, pp. 319-351.
5. 4. Gensler, W.J.; Gatsonis, C.D. J. Org. Chem. 1966, 31, 3224, 4004 and earlier references cited therein.
6. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
7. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
8. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
9. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
10. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
11. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
12. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
13. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
14. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
15. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
16. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
17. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
18. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
19. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
20. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
21. 5. For total synthesis of 1, see : MacDonald, D.I.; Durst, T. J. Org. Chem. 1988, 53, 3663. Jones, D.W.; Thompson, A.M. J. Chem. Soc., Chem. Commun. 1987, 1797. Vyas, D.M.; Skonezny, P.M.; Jenks, T.A.; Doyle, T.W. Tetrahedron Lett. 1986, 27, 3099. Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517. MacDonald, D.I.; Durst, T. J. Org. Chem. 1986, 51, 4749. Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826. Kende, A.S. Liebeskind, L.S.; Mills, J.E.; Rutledge, P.S.; Curran, D.P. J. Am. Chem. Soc. 1977, 99, 7082. Forsey, S.P.; Rajapakska, D.; Taylor, N.J.; Rodrigo, R.J. J. Org. Chem. 1989, 54, 4280. Van der Eycken, J.; De Clercq, P.; Vandewalle, M. Tetrahedron 1986, 42, 4297. For reviews on the synthesis of podophyllotoxins, see : Ward, R.S. Chem. Soc. Rev. 1982, 11, 75. Whiting, D.A. Nat. Prod. Rep. 1985, 2, 191; 1987, 4, 499; 1990, 7, 349. Ward, R.S. Tetrahedron 1990, 46, 5029. Ward, R.S. Synthesis 1992, 719.
22. 6. Kende, A.S.; King, M.L.; Curran, D.P. J. Org. Chem. 1981, 46, 2826.
23. 7. Van Speybroeck, R.; Guo, H.; Van der Eycken, J.; Vandewalle, M. Tetrahedron 1991, 47, 4675.
24. 8. Andrews, R.C.; Teague, S.J.; Meyers, A.I. J. Am. Chem. Soc. 1988, 110, 7854.
25. 9. Bush, E.J.; Jones, D.W. J. Chem. Soc., Chem. Commun. 1993, 1200. Bush, E.J.; Jones, D.W. J. Chem. Soc., Perkin Trans I 1996, 151.
26. 9. Bush, E.J.; Jones, D.W. J. Chem. Soc., Chem. Commun. 1993, 1200. Bush, E.J.; Jones, D.W. J. Chem. Soc., Perkin Trans I 1996, 151.
27. 10. Loike, J.D.; Brewer, C.F.; Sternlich, H.; Gensler, W.J., Horwitz, S. B. Cancer Res. 1978, 38, 2688. Wilson, L.; Friedkin, M. Biochemistry 1967, 6, 3126.
28. 10. Loike, J.D.; Brewer, C.F.; Sternlich, H.; Gensler, W.J., Horwitz, S. B. Cancer Res. 1978, 38, 2688. Wilson, L.; Friedkin, M. Biochemistry 1967, 6, 3126.
29. 11. Sackett, D.L. Pharmacol. Ther. 1993, 59, 163.
30. 12. Bender, R.A.; Hamel, E.; Hande, K.R. 1990 Plant Alkaloids. In : Chabner, B.A.; Collins, J.M. eds Cancer Chemotherapy. J.B. Lippincott, New York, pp. 253-275.
31. 13. Keller-Juslen, C.; Kuhn, M.; von Wartburg, A.; Stähelin, H.F. J. Med. Chem. 1971, 14, 936. Stähelin, H.F.; von Wartburg A. Cancer Res. 1991, 51, 5.
32. 13. Keller-Juslen, C.; Kuhn, M.; von Wartburg, A.; Stähelin, H.F. J. Med. Chem. 1971, 14, 936. Stähelin, H.F.; von Wartburg A. Cancer Res. 1991, 51, 5.
33. 14. Ayres, D.C.; Loike, J.D. Lignans. Chemical, biological and clinical properties, Chp. 3 and 4; Cambridge University Press; Cambridge 1990. Issell, B.F.; Muggia, F.M.; Carter, S.K. Etoposide [VP-16] Current Status and New Developments; Academic Press : Orlando, 1984, pp. 1-353. O'Dwyer, P.J.; Leyland-Jones, B.; Alonso, M.T.; Marsoni, S.; Wittes, R.E. N. Engl. J. Med. 1985, 312, 692.
34. 14. Ayres, D.C.; Loike, J.D. Lignans. Chemical, biological and clinical properties, Chp. 3 and 4; Cambridge University Press; Cambridge 1990. Issell, B.F.; Muggia, F.M.; Carter, S.K. Etoposide [VP-16] Current Status and New Developments; Academic Press : Orlando, 1984, pp. 1-353. O'Dwyer, P.J.; Leyland-Jones, B.; Alonso, M.T.; Marsoni, S.; Wittes, R.E. N. Engl. J. Med. 1985, 312, 692.
35. 14. Ayres, D.C.; Loike, J.D. Lignans. Chemical, biological and clinical properties, Chp. 3 and 4; Cambridge University Press; Cambridge 1990. Issell, B.F.; Muggia, F.M.; Carter, S.K. Etoposide [VP-16] Current Status and New Developments; Academic Press : Orlando, 1984, pp. 1-353. O'Dwyer, P.J.; Leyland-Jones, B.; Alonso, M.T.; Marsoni, S.; Wittes, R.E. N. Engl. J. Med. 1985, 312, 692.
36. 15. Chapman, R.; Itri, L.; Gralla, R.; Kelsen, D.; Capser, E.; Golby, R. Cancer Chemother. Pharmacol. 1982, 7, 205. Eagan, R.; Carr, D.; Frytak, S. Cancer Treat. Rep. 1976, 60, 949.
37. 15. Chapman, R.; Itri, L.; Gralla, R.; Kelsen, D.; Capser, E.; Golby, R. Cancer Chemother. Pharmacol. 1982, 7, 205. Eagan, R.; Carr, D.; Frytak, S. Cancer Treat. Rep. 1976, 60, 949.
38. 16. Van Maanen, J.M.S.; Retel, J.; de Vries, J.; Pinedo, H.M. J. Natl. Cancer Inst. 1988, 80, 1526. Long, B.H. NCI Monographs 1987, No 4, 123. Chen, G. L.; Yang, L.; Rowe, T.C.; Halligan, B.D.; Tewey, K.; Kiu, L. J. Biol. Chem. 1984, 259, 13560. Ross, W.; Rowe, T.; Glisson, B.; Yalowich, J.; Liu, L. Cancer Res. 1984, 44, 5857. Rowe, T.; Kuppfer, G.; Ross, W. Biochem. Pharmacol. 1985, 34, 2483. Long, B.H.; Minocha, A. Proc. Am. Assoc. Cancer Res. 1983, 24, 321 Abstr.. Minocha, A.; Long, B.H. Biochem. Biophys. Res. Commun. 1984, 122, 165.
39. 16. Van Maanen, J.M.S.; Retel, J.; de Vries, J.; Pinedo, H.M. J. Natl. Cancer Inst. 1988, 80, 1526. Long, B.H. NCI Monographs 1987, No 4, 123. Chen, G. L.; Yang, L.; Rowe, T.C.; Halligan, B.D.; Tewey, K.; Kiu, L. J. Biol. Chem. 1984, 259, 13560. Ross, W.; Rowe, T.; Glisson, B.; Yalowich, J.; Liu, L. Cancer Res. 1984, 44, 5857. Rowe, T.; Kuppfer, G.; Ross, W. Biochem. Pharmacol. 1985, 34, 2483. Long, B.H.; Minocha, A. Proc. Am. Assoc. Cancer Res. 1983, 24, 321 Abstr.. Minocha, A.; Long, B.H. Biochem. Biophys. Res. Commun. 1984, 122, 165.
40. 16. Van Maanen, J.M.S.; Retel, J.; de Vries, J.; Pinedo, H.M. J. Natl. Cancer Inst. 1988, 80, 1526. Long, B.H. NCI Monographs 1987, No 4, 123. Chen, G. L.; Yang, L.; Rowe, T.C.; Halligan, B.D.; Tewey, K.; Kiu, L. J. Biol. Chem. 1984, 259, 13560. Ross, W.; Rowe, T.; Glisson, B.; Yalowich, J.; Liu, L. Cancer Res. 1984, 44, 5857. Rowe, T.; Kuppfer, G.; Ross, W. Biochem. Pharmacol. 1985, 34, 2483. Long, B.H.; Minocha, A. Proc. Am. Assoc. Cancer Res. 1983, 24, 321 Abstr.. Minocha, A.; Long, B.H. Biochem. Biophys. Res. Commun. 1984, 122, 165.
41. 16. Van Maanen, J.M.S.; Retel, J.; de Vries, J.; Pinedo, H.M. J. Natl. Cancer Inst. 1988, 80, 1526. Long, B.H. NCI Monographs 1987, No 4, 123. Chen, G. L.; Yang, L.; Rowe, T.C.; Halligan, B.D.; Tewey, K.; Kiu, L. J. Biol. Chem. 1984, 259, 13560. Ross, W.; Rowe, T.; Glisson, B.; Yalowich, J.; Liu, L. Cancer Res. 1984, 44, 5857. Rowe, T.; Kuppfer, G.; Ross, W. Biochem. Pharmacol. 1985, 34, 2483. Long, B.H.; Minocha, A. Proc. Am. Assoc. Cancer Res. 1983, 24, 321 Abstr.. Minocha, A.; Long, B.H. Biochem. Biophys. Res. Commun. 1984, 122, 165.
42. 16. Van Maanen, J.M.S.; Retel, J.; de Vries, J.; Pinedo, H.M. J. Natl. Cancer Inst. 1988, 80, 1526. Long, B.H. NCI Monographs 1987, No 4, 123. Chen, G. L.; Yang, L.; Rowe, T.C.; Halligan, B.D.; Tewey, K.; Kiu, L. J. Biol. Chem. 1984, 259, 13560. Ross, W.; Rowe, T.; Glisson, B.; Yalowich, J.; Liu, L. Cancer Res. 1984, 44, 5857. Rowe, T.; Kuppfer, G.; Ross, W. Biochem. Pharmacol. 1985, 34, 2483. Long, B.H.; Minocha, A. Proc. Am. Assoc. Cancer Res. 1983, 24, 321 Abstr.. Minocha, A.; Long, B.H. Biochem. Biophys. Res. Commun. 1984, 122, 165.
43. 16. Van Maanen, J.M.S.; Retel, J.; de Vries, J.; Pinedo, H.M. J. Natl. Cancer Inst. 1988, 80, 1526. Long, B.H. NCI Monographs 1987, No 4, 123. Chen, G. L.; Yang, L.; Rowe, T.C.; Halligan, B.D.; Tewey, K.; Kiu, L. J. Biol. Chem. 1984, 259, 13560. Ross, W.; Rowe, T.; Glisson, B.; Yalowich, J.; Liu, L. Cancer Res. 1984, 44, 5857. Rowe, T.; Kuppfer, G.; Ross, W. Biochem. Pharmacol. 1985, 34, 2483. Long, B.H.; Minocha, A. Proc. Am. Assoc. Cancer Res. 1983, 24, 321 Abstr.. Minocha, A.; Long, B.H. Biochem. Biophys. Res. Commun. 1984, 122, 165.
44. 16. Van Maanen, J.M.S.; Retel, J.; de Vries, J.; Pinedo, H.M. J. Natl. Cancer Inst. 1988, 80, 1526. Long, B.H. NCI Monographs 1987, No 4, 123. Chen, G. L.; Yang, L.; Rowe, T.C.; Halligan, B.D.; Tewey, K.; Kiu, L. J. Biol. Chem. 1984, 259, 13560. Ross, W.; Rowe, T.; Glisson, B.; Yalowich, J.; Liu, L. Cancer Res. 1984, 44, 5857. Rowe, T.; Kuppfer, G.; Ross, W. Biochem. Pharmacol. 1985, 34, 2483. Long, B.H.; Minocha, A. Proc. Am. Assoc. Cancer Res. 1983, 24, 321 Abstr.. Minocha, A.; Long, B.H. Biochem. Biophys. Res. Commun. 1984, 122, 165.
45. 17. Sinha, B.K.; Trust, M.A. Biochem. Pharmacol. 1983, 32, 3495. Sinha, B.K.; Myers, C.E. Ibid. 1984, 33, 3725. Haim, N.; Nemec, J.; Roman, J.; Sinha, B.K. Ibid. 1987, 36, 527. Vyas, D.M.; Kadow, J.F.; Le Boulluec, K.L.; Saulnier, M.G.; Doyle, T.W. Bioorg. Med. Chem. Lett. 1992, 2, 1111.
46. 17. Sinha, B.K.; Trust, M.A. Biochem. Pharmacol. 1983, 32, 3495. Sinha, B.K.; Myers, C.E. Ibid. 1984, 33, 3725. Haim, N.; Nemec, J.; Roman, J.; Sinha, B.K. Ibid. 1987, 36, 527. Vyas, D.M.; Kadow, J.F.; Le Boulluec, K.L.; Saulnier, M.G.; Doyle, T.W. Bioorg. Med. Chem. Lett. 1992, 2, 1111.
47. 17. Sinha, B.K.; Trust, M.A. Biochem. Pharmacol. 1983, 32, 3495. Sinha, B.K.; Myers, C.E. Ibid. 1984, 33, 3725. Haim, N.; Nemec, J.; Roman, J.; Sinha, B.K. Ibid. 1987, 36, 527. Vyas, D.M.; Kadow, J.F.; Le Boulluec, K.L.; Saulnier, M.G.; Doyle, T.W. Bioorg. Med. Chem. Lett. 1992, 2, 1111.
48. 17. Sinha, B.K.; Trust, M.A. Biochem. Pharmacol. 1983, 32, 3495. Sinha, B.K.; Myers, C.E. Ibid. 1984, 33, 3725. Haim, N.; Nemec, J.; Roman, J.; Sinha, B.K. Ibid. 1987, 36, 527. Vyas, D.M.; Kadow, J.F.; Le Boulluec, K.L.; Saulnier, M.G.; Doyle, T.W. Bioorg. Med. Chem. Lett. 1992, 2, 1111.
49. 18. Shah, J.C.; Chen, J.R.; Chow, D. Pharm. Res. 1989, 6, 408.
50. 19. Hande, K.; Anthony, L.; Hamilton, R.; Bennet, R.; Sweetman, B.; Branch, R. Cancer Res. 1988, 48, 1829. Creaven, P.J. Cancer Chemother. Pharmacol. 1982, 7, 133. Evans, W.E.; Sinkule, J.A.; Crom, W.R.; Dow, L., Look, A.T.; Rivera, G. Cancer Chemother. Pharmacol. 1982, 7, 147. Brewer, C.F.; Loike, J.D.; Horwitz, S.B.; Sternlicht, H.; Gensler, W.J. J. Med. Chem. 1979, 22, 215. Dow, L.W.; Sinkull, J.A.; Look, A.T.; Horvath, A.; Evans, W.E. Cancer Res. 1983, 43, 5699. Emmeneger, H.; Stähelin, J.; Rutschmann, J.; Renz, J.; von Wartburg, A. Arzneim.-Forsch. 1961, 11, 327, 459.
51. 19. Hande, K.; Anthony, L.; Hamilton, R.; Bennet, R.; Sweetman, B.; Branch, R. Cancer Res. 1988, 48, 1829. Creaven, P.J. Cancer Chemother. Pharmacol. 1982, 7, 133. Evans, W.E.; Sinkule, J.A.; Crom, W.R.; Dow, L., Look, A.T.; Rivera, G. Cancer Chemother. Pharmacol. 1982, 7, 147. Brewer, C.F.; Loike, J.D.; Horwitz, S.B.; Sternlicht, H.; Gensler, W.J. J. Med. Chem. 1979, 22, 215. Dow, L.W.; Sinkull, J.A.; Look, A.T.; Horvath, A.; Evans, W.E. Cancer Res. 1983, 43, 5699. Emmeneger, H.; Stähelin, J.; Rutschmann, J.; Renz, J.; von Wartburg, A. Arzneim.-Forsch. 1961, 11, 327, 459.
52. 19. Hande, K.; Anthony, L.; Hamilton, R.; Bennet, R.; Sweetman, B.; Branch, R. Cancer Res. 1988, 48, 1829. Creaven, P.J. Cancer Chemother. Pharmacol. 1982, 7, 133. Evans, W.E.; Sinkule, J.A.; Crom, W.R.; Dow, L., Look, A.T.; Rivera, G. Cancer Chemother. Pharmacol. 1982, 7, 147. Brewer, C.F.; Loike, J.D.; Horwitz, S.B.; Sternlicht, H.; Gensler, W.J. J. Med. Chem. 1979, 22, 215. Dow, L.W.; Sinkull, J.A.; Look, A.T.; Horvath, A.; Evans, W.E. Cancer Res. 1983, 43, 5699. Emmeneger, H.; Stähelin, J.; Rutschmann, J.; Renz, J.; von Wartburg, A. Arzneim.-Forsch. 1961, 11, 327, 459.
53. 19. Hande, K.; Anthony, L.; Hamilton, R.; Bennet, R.; Sweetman, B.; Branch, R. Cancer Res. 1988, 48, 1829. Creaven, P.J. Cancer Chemother. Pharmacol. 1982, 7, 133. Evans, W.E.; Sinkule, J.A.; Crom, W.R.; Dow, L., Look, A.T.; Rivera, G. Cancer Chemother. Pharmacol. 1982, 7, 147. Brewer, C.F.; Loike, J.D.; Horwitz, S.B.; Sternlicht, H.; Gensler, W.J. J. Med. Chem. 1979, 22, 215. Dow, L.W.; Sinkull, J.A.; Look, A.T.; Horvath, A.; Evans, W.E. Cancer Res. 1983, 43, 5699. Emmeneger, H.; Stähelin, J.; Rutschmann, J.; Renz, J.; von Wartburg, A. Arzneim.-Forsch. 1961, 11, 327, 459.
54. 19. Hande, K.; Anthony, L.; Hamilton, R.; Bennet, R.; Sweetman, B.; Branch, R. Cancer Res. 1988, 48, 1829. Creaven, P.J. Cancer Chemother. Pharmacol. 1982, 7, 133. Evans, W.E.; Sinkule, J.A.; Crom, W.R.; Dow, L., Look, A.T.; Rivera, G. Cancer Chemother. Pharmacol. 1982, 7, 147. Brewer, C.F.; Loike, J.D.; Horwitz, S.B.; Sternlicht, H.; Gensler, W.J. J. Med. Chem. 1979, 22, 215. Dow, L.W.; Sinkull, J.A.; Look, A.T.; Horvath, A.; Evans, W.E. Cancer Res. 1983, 43, 5699. Emmeneger, H.; Stähelin, J.; Rutschmann, J.; Renz, J.; von Wartburg, A. Arzneim.-Forsch. 1961, 11, 327, 459.
55. 19. Hande, K.; Anthony, L.; Hamilton, R.; Bennet, R.; Sweetman, B.; Branch, R. Cancer Res. 1988, 48, 1829. Creaven, P.J. Cancer Chemother. Pharmacol. 1982, 7, 133. Evans, W.E.; Sinkule, J.A.; Crom, W.R.; Dow, L., Look, A.T.; Rivera, G. Cancer Chemother. Pharmacol. 1982, 7, 147. Brewer, C.F.; Loike, J.D.; Horwitz, S.B.; Sternlicht, H.; Gensler, W.J. J. Med. Chem. 1979, 22, 215. Dow, L.W.; Sinkull, J.A.; Look, A.T.; Horvath, A.; Evans, W.E. Cancer Res. 1983, 43, 5699. Emmeneger, H.; Stähelin, J.; Rutschmann, J.; Renz, J.; von Wartburg, A. Arzneim.-Forsch. 1961, 11, 327, 459.
56. 20. See for example : Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.-i.; Wierzba, K.; Kobunai, T.; Takeda, S.; Minami, Y.; Yoshida, K.-i.; Yamaguchi, H.; Yamada, Y. Chem. Pharm. Bull. 1993, 41, 907. Miyahara, M.; Kashiwada, Y.; Guo, X.; Chen, H.-X.; Cheng, C.; Lee, K.-H. Heterocycles 1994, 39, 361. Lee, K.-H.; Beers, S.A.; Mori, M.; Wang, Z.-Q.; Kuo, Y.-H.; Li, L.; Liu, S.-Y.; Chang, J.-Y.; Han, F.-S.; Cheng, Y.-C. J. Med. Chem. 1990, 33, 1364. Klein, L.L.; Yeung, C.M.; Chu, D.T.; McDonald, E.J.; Clement, J.J.; Plattner, J.J. J. Med. Chem. 1991, 34, 984. Gensler, W.J.; Murthy, C.D.; Trammell, M.H. J. Med. Chem. 1977, 20, 635. Wang, J.-Z.; Tian, X.; Tsumora, H.; Shimura, K.; Ito, H. Anti-Cancer Drug Design 1993, 8, 193. Mc Combie, S.W.; Tagat, J.R.; Metz, W.A.; Nazareno, D.; Puar, M.S. Tetrahedron 1993, 49, 8073.
57. 20. See for example : Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.-i.; Wierzba, K.; Kobunai, T.; Takeda, S.; Minami, Y.; Yoshida, K.-i.; Yamaguchi, H.; Yamada, Y. Chem. Pharm. Bull. 1993, 41, 907. Miyahara, M.; Kashiwada, Y.; Guo, X.; Chen, H.-X.; Cheng, C.; Lee, K.-H. Heterocycles 1994, 39, 361. Lee, K.-H.; Beers, S.A.; Mori, M.; Wang, Z.-Q.; Kuo, Y.-H.; Li, L.; Liu, S.-Y.; Chang, J.-Y.; Han, F.-S.; Cheng, Y.-C. J. Med. Chem. 1990, 33, 1364. Klein, L.L.; Yeung, C.M.; Chu, D.T.; McDonald, E.J.; Clement, J.J.; Plattner, J.J. J. Med. Chem. 1991, 34, 984. Gensler, W.J.; Murthy, C.D.; Trammell, M.H. J. Med. Chem. 1977, 20, 635. Wang, J.-Z.; Tian, X.; Tsumora, H.; Shimura, K.; Ito, H. Anti-Cancer Drug Design 1993, 8, 193. Mc Combie, S.W.; Tagat, J.R.; Metz, W.A.; Nazareno, D.; Puar, M.S. Tetrahedron 1993, 49, 8073.
58. 20. See for example : Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.-i.; Wierzba, K.; Kobunai, T.; Takeda, S.; Minami, Y.; Yoshida, K.-i.; Yamaguchi, H.; Yamada, Y. Chem. Pharm. Bull. 1993, 41, 907. Miyahara, M.; Kashiwada, Y.; Guo, X.; Chen, H.-X.; Cheng, C.; Lee, K.-H. Heterocycles 1994, 39, 361. Lee, K.-H.; Beers, S.A.; Mori, M.; Wang, Z.-Q.; Kuo, Y.-H.; Li, L.; Liu, S.-Y.; Chang, J.-Y.; Han, F.-S.; Cheng, Y.-C. J. Med. Chem. 1990, 33, 1364. Klein, L.L.; Yeung, C.M.; Chu, D.T.; McDonald, E.J.; Clement, J.J.; Plattner, J.J. J. Med. Chem. 1991, 34, 984. Gensler, W.J.; Murthy, C.D.; Trammell, M.H. J. Med. Chem. 1977, 20, 635. Wang, J.-Z.; Tian, X.; Tsumora, H.; Shimura, K.; Ito, H. Anti-Cancer Drug Design 1993, 8, 193. Mc Combie, S.W.; Tagat, J.R.; Metz, W.A.; Nazareno, D.; Puar, M.S. Tetrahedron 1993, 49, 8073.
59. 20. See for example : Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.-i.; Wierzba, K.; Kobunai, T.; Takeda, S.; Minami, Y.; Yoshida, K.-i.; Yamaguchi, H.; Yamada, Y. Chem. Pharm. Bull. 1993, 41, 907. Miyahara, M.; Kashiwada, Y.; Guo, X.; Chen, H.-X.; Cheng, C.; Lee, K.-H. Heterocycles 1994, 39, 361. Lee, K.-H.; Beers, S.A.; Mori, M.; Wang, Z.-Q.; Kuo, Y.-H.; Li, L.; Liu, S.-Y.; Chang, J.-Y.; Han, F.-S.; Cheng, Y.-C. J. Med. Chem. 1990, 33, 1364. Klein, L.L.; Yeung, C.M.; Chu, D.T.; McDonald, E.J.; Clement, J.J.; Plattner, J.J. J. Med. Chem. 1991, 34, 984. Gensler, W.J.; Murthy, C.D.; Trammell, M.H. J. Med. Chem. 1977, 20, 635. Wang, J.-Z.; Tian, X.; Tsumora, H.; Shimura, K.; Ito, H. Anti-Cancer Drug Design 1993, 8, 193. Mc Combie, S.W.; Tagat, J.R.; Metz, W.A.; Nazareno, D.; Puar, M.S. Tetrahedron 1993, 49, 8073.
60. 20. See for example : Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.-i.; Wierzba, K.; Kobunai, T.; Takeda, S.; Minami, Y.; Yoshida, K.-i.; Yamaguchi, H.; Yamada, Y. Chem. Pharm. Bull. 1993, 41, 907. Miyahara, M.; Kashiwada, Y.; Guo, X.; Chen, H.-X.; Cheng, C.; Lee, K.-H. Heterocycles 1994, 39, 361. Lee, K.-H.; Beers, S.A.; Mori, M.; Wang, Z.-Q.; Kuo, Y.-H.; Li, L.; Liu, S.-Y.; Chang, J.-Y.; Han, F.-S.; Cheng, Y.-C. J. Med. Chem. 1990, 33, 1364. Klein, L.L.; Yeung, C.M.; Chu, D.T.; McDonald, E.J.; Clement, J.J.; Plattner, J.J. J. Med. Chem. 1991, 34, 984. Gensler, W.J.; Murthy, C.D.; Trammell, M.H. J. Med. Chem. 1977, 20, 635. Wang, J.-Z.; Tian, X.; Tsumora, H.; Shimura, K.; Ito, H. Anti-Cancer Drug Design 1993, 8, 193. Mc Combie, S.W.; Tagat, J.R.; Metz, W.A.; Nazareno, D.; Puar, M.S. Tetrahedron 1993, 49, 8073.
61. 20. See for example : Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.-i.; Wierzba, K.; Kobunai, T.; Takeda, S.; Minami, Y.; Yoshida, K.-i.; Yamaguchi, H.; Yamada, Y. Chem. Pharm. Bull. 1993, 41, 907. Miyahara, M.; Kashiwada, Y.; Guo, X.; Chen, H.-X.; Cheng, C.; Lee, K.-H. Heterocycles 1994, 39, 361. Lee, K.-H.; Beers, S.A.; Mori, M.; Wang, Z.-Q.; Kuo, Y.-H.; Li, L.; Liu, S.-Y.; Chang, J.-Y.; Han, F.-S.; Cheng, Y.-C. J. Med. Chem. 1990, 33, 1364. Klein, L.L.; Yeung, C.M.; Chu, D.T.; McDonald, E.J.; Clement, J.J.; Plattner, J.J. J. Med. Chem. 1991, 34, 984. Gensler, W.J.; Murthy, C.D.; Trammell, M.H. J. Med. Chem. 1977, 20, 635. Wang, J.-Z.; Tian, X.; Tsumora, H.; Shimura, K.; Ito, H. Anti-Cancer Drug Design 1993, 8, 193. Mc Combie, S.W.; Tagat, J.R.; Metz, W.A.; Nazareno, D.; Puar, M.S. Tetrahedron 1993, 49, 8073.
62. 20. See for example : Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.-i.; Wierzba, K.; Kobunai, T.; Takeda, S.; Minami, Y.; Yoshida, K.-i.; Yamaguchi, H.; Yamada, Y. Chem. Pharm. Bull. 1993, 41, 907. Miyahara, M.; Kashiwada, Y.; Guo, X.; Chen, H.-X.; Cheng, C.; Lee, K.-H. Heterocycles 1994, 39, 361. Lee, K.-H.; Beers, S.A.; Mori, M.; Wang, Z.-Q.; Kuo, Y.-H.; Li, L.; Liu, S.-Y.; Chang, J.-Y.; Han, F.-S.; Cheng, Y.-C. J. Med. Chem. 1990, 33, 1364. Klein, L.L.; Yeung, C.M.; Chu, D.T.; McDonald, E.J.; Clement, J.J.; Plattner, J.J. J. Med. Chem. 1991, 34, 984. Gensler, W.J.; Murthy, C.D.; Trammell, M.H. J. Med. Chem. 1977, 20, 635. Wang, J.-Z.; Tian, X.; Tsumora, H.; Shimura, K.; Ito, H. Anti-Cancer Drug Design 1993, 8, 193. Mc Combie, S.W.; Tagat, J.R.; Metz, W.A.; Nazareno, D.; Puar, M.S. Tetrahedron 1993, 49, 8073.
63. 21. Long, B. H.; Casazza A.-M. Cancer Chemother. Pharmacol. 1994, 34, 526.
64. 22. Van der Eycken, J.; Bosmans, J.-P.; Van Haver, D.; Vandewalle, M. ; Hulkenberg, A.; Veerman, W.; Nieuwenhuizen, R. Tetrahedron Lett. 1989, 30, 3873. Bosmans, J.-P.; Van der Eycken, J.; Vandewalle, M.; Hulkenberg, A.; Van Hes, R.; Veerman, W. Tetrahedron Lett. 1989, 30, 3877. Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron Lett. 1989, 30, 2953; Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron 1993, 49, 1891. Tomioka, K. Kubota, Y.; Koga, K. J. Chem. Soc., Chem. Commun. 1989, 1622. Pearce, H.L.; Bach, N.J.; Cramer, T.L. Tetrahedron Lett. 1989, 30, 907. Lienard, P.; Quirion, J.-C.; Husson, H.-P. Tetrahedron 1993, 49, 3995.
65. 22. Van der Eycken, J.; Bosmans, J.-P.; Van Haver, D.; Vandewalle, M. ; Hulkenberg, A.; Veerman, W.; Nieuwenhuizen, R. Tetrahedron Lett. 1989, 30, 3873. Bosmans, J.-P.; Van der Eycken, J.; Vandewalle, M.; Hulkenberg, A.; Van Hes, R.; Veerman, W. Tetrahedron Lett. 1989, 30, 3877. Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron Lett. 1989, 30, 2953; Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron 1993, 49, 1891. Tomioka, K. Kubota, Y.; Koga, K. J. Chem. Soc., Chem. Commun. 1989, 1622. Pearce, H.L.; Bach, N.J.; Cramer, T.L. Tetrahedron Lett. 1989, 30, 907. Lienard, P.; Quirion, J.-C.; Husson, H.-P. Tetrahedron 1993, 49, 3995.
66. 22. Van der Eycken, J.; Bosmans, J.-P.; Van Haver, D.; Vandewalle, M. ; Hulkenberg, A.; Veerman, W.; Nieuwenhuizen, R. Tetrahedron Lett. 1989, 30, 3873. Bosmans, J.-P.; Van der Eycken, J.; Vandewalle, M.; Hulkenberg, A.; Van Hes, R.; Veerman, W. Tetrahedron Lett. 1989, 30, 3877. Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron Lett. 1989, 30, 2953; Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron 1993, 49, 1891. Tomioka, K. Kubota, Y.; Koga, K. J. Chem. Soc., Chem. Commun. 1989, 1622. Pearce, H.L.; Bach, N.J.; Cramer, T.L. Tetrahedron Lett. 1989, 30, 907. Lienard, P.; Quirion, J.-C.; Husson, H.-P. Tetrahedron 1993, 49, 3995.
67. 22. Van der Eycken, J.; Bosmans, J.-P.; Van Haver, D.; Vandewalle, M. ; Hulkenberg, A.; Veerman, W.; Nieuwenhuizen, R. Tetrahedron Lett. 1989, 30, 3873. Bosmans, J.-P.; Van der Eycken, J.; Vandewalle, M.; Hulkenberg, A.; Van Hes, R.; Veerman, W. Tetrahedron Lett. 1989, 30, 3877. Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron Lett. 1989, 30, 2953; Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron 1993, 49, 1891. Tomioka, K. Kubota, Y.; Koga, K. J. Chem. Soc., Chem. Commun. 1989, 1622. Pearce, H.L.; Bach, N.J.; Cramer, T.L. Tetrahedron Lett. 1989, 30, 907. Lienard, P.; Quirion, J.-C.; Husson, H.-P. Tetrahedron 1993, 49, 3995.
68. 22. Van der Eycken, J.; Bosmans, J.-P.; Van Haver, D.; Vandewalle, M. ; Hulkenberg, A.; Veerman, W.; Nieuwenhuizen, R. Tetrahedron Lett. 1989, 30, 3873. Bosmans, J.-P.; Van der Eycken, J.; Vandewalle, M.; Hulkenberg, A.; Van Hes, R.; Veerman, W. Tetrahedron Lett. 1989, 30, 3877. Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron Lett. 1989, 30, 2953; Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron 1993, 49, 1891. Tomioka, K. Kubota, Y.; Koga, K. J. Chem. Soc., Chem. Commun. 1989, 1622. Pearce, H.L.; Bach, N.J.; Cramer, T.L. Tetrahedron Lett. 1989, 30, 907. Lienard, P.; Quirion, J.-C.; Husson, H.-P. Tetrahedron 1993, 49, 3995.
69. 22. Van der Eycken, J.; Bosmans, J.-P.; Van Haver, D.; Vandewalle, M. ; Hulkenberg, A.; Veerman, W.; Nieuwenhuizen, R. Tetrahedron Lett. 1989, 30, 3873. Bosmans, J.-P.; Van der Eycken, J.; Vandewalle, M.; Hulkenberg, A.; Van Hes, R.; Veerman, W. Tetrahedron Lett. 1989, 30, 3877. Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron Lett. 1989, 30, 2953; Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron 1993, 49, 1891. Tomioka, K. Kubota, Y.; Koga, K. J. Chem. Soc., Chem. Commun. 1989, 1622. Pearce, H.L.; Bach, N.J.; Cramer, T.L. Tetrahedron Lett. 1989, 30, 907. Lienard, P.; Quirion, J.-C.; Husson, H.-P. Tetrahedron 1993, 49, 3995.
70. 22. Van der Eycken, J.; Bosmans, J.-P.; Van Haver, D.; Vandewalle, M. ; Hulkenberg, A.; Veerman, W.; Nieuwenhuizen, R. Tetrahedron Lett. 1989, 30, 3873. Bosmans, J.-P.; Van der Eycken, J.; Vandewalle, M.; Hulkenberg, A.; Van Hes, R.; Veerman, W. Tetrahedron Lett. 1989, 30, 3877. Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron Lett. 1989, 30, 2953; Tomioka, K.; Kubota, Y.; Koga, K. Tetrahedron 1993, 49, 1891. Tomioka, K. Kubota, Y.; Koga, K. J. Chem. Soc., Chem. Commun. 1989, 1622. Pearce, H.L.; Bach, N.J.; Cramer, T.L. Tetrahedron Lett. 1989, 30, 907. Lienard, P.; Quirion, J.-C.; Husson, H.-P. Tetrahedron 1993, 49, 3995.
71. 23. Hitotsuyanagi, Y.; Yamagami, K.; Fujii, A.; Naka, Y.; Tahara, T. J. Chem. Soc., Chem. Commun. 1995, 49. Hitotsuyanagi, Y.; Naka, Y.; Yamagami, K.; Fujii, A.; Ito, Y.; Tahara, T. Bioorg. Med. Chem. Lett. 1995, 5, 1039.
72. 23. Hitotsuyanagi, Y.; Yamagami, K.; Fujii, A.; Naka, Y.; Tahara, T. J. Chem. Soc., Chem. Commun. 1995, 49. Hitotsuyanagi, Y.; Naka, Y.; Yamagami, K.; Fujii, A.; Ito, Y.; Tahara, T. Bioorg. Med. Chem. Lett. 1995, 5, 1039.
73. 24. Hitotsuyanagi, Y.; Ichihara, Y.; Takeya, K; Itokawa H. Tetrahedron Lett. 1994, 35, 9401.
74. 25. Hitotsuyanagi, Y.; Kobayashi, M.; Takeya, K.; Itokawa, H. J. Chem. Soc. Perkin Trans I 1995, 1387.
75. 26. The synthesis and biological evaluation of podophenazine analogues have just been reported: Cho, S.J., Kashiwada, Y.; Bastow, K.F.; Cheng, Y.-C., Lee, K.-H. J. Med. Chem. 1996, 39, 1396.
76. 27. Podophyllotoxin, see : Wang, Z.-Q.; Hu, H.; Chen, H.-X.; Cheng, Y.-C.; Lee, K.-H. J. Med. Chem. 1992, 35, 871. Etoposide, see : Kadow, J.F.; Tun, M.M.; Crosswell, A.R.; Rose, W.C.; Vyas, D.M.; Doyle, T.W. Bioorg. Med. Chem. Lett. 1992, 2, 17.
77. 27. Podophyllotoxin, see : Wang, Z.-Q.; Hu, H.; Chen, H.-X.; Cheng, Y.-C.; Lee, K.-H. J. Med. Chem. 1992, 35, 871. Etoposide, see : Kadow, J.F.; Tun, M.M.; Crosswell, A.R.; Rose, W.C.; Vyas, D.M.; Doyle, T.W. Bioorg. Med. Chem. Lett. 1992, 2, 17.
78. 28. Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. Stille, J.K. Pure Appl. Chem. 1985, 57, 1771. Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1987, 109, 5478. Mitchell, T.N. Synthesis 1992, 803. Farina, V.; Krishnan, B.; Marshall, D.R.; Roth, G.P. J. Org. Chem. 1993, 58, 5434. Farina, V.; Kapadia, S.; Krishnan, B., Wang, C.; Liebeskind, L.S. J. Org. Chem. 1994, 59, 5905. Roth, G.P.; Farina, V.; Liebeskind, L.S.; Peña-Cabrera E. Tetrahedron Lett. 1995, 36, 2191. Morita, D.K.; Stille, J.K.; Norton, J.R. J. Am. Chem. Soc. 1995, 117, 8576.
79. 28. Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. Stille, J.K. Pure Appl. Chem. 1985, 57, 1771. Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1987, 109, 5478. Mitchell, T.N. Synthesis 1992, 803. Farina, V.; Krishnan, B.; Marshall, D.R.; Roth, G.P. J. Org. Chem. 1993, 58, 5434. Farina, V.; Kapadia, S.; Krishnan, B., Wang, C.; Liebeskind, L.S. J. Org. Chem. 1994, 59, 5905. Roth, G.P.; Farina, V.; Liebeskind, L.S.; Peña-Cabrera E. Tetrahedron Lett. 1995, 36, 2191. Morita, D.K.; Stille, J.K.; Norton, J.R. J. Am. Chem. Soc. 1995, 117, 8576.
80. 28. Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. Stille, J.K. Pure Appl. Chem. 1985, 57, 1771. Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1987, 109, 5478. Mitchell, T.N. Synthesis 1992, 803. Farina, V.; Krishnan, B.; Marshall, D.R.; Roth, G.P. J. Org. Chem. 1993, 58, 5434. Farina, V.; Kapadia, S.; Krishnan, B., Wang, C.; Liebeskind, L.S. J. Org. Chem. 1994, 59, 5905. Roth, G.P.; Farina, V.; Liebeskind, L.S.; Peña-Cabrera E. Tetrahedron Lett. 1995, 36, 2191. Morita, D.K.; Stille, J.K.; Norton, J.R. J. Am. Chem. Soc. 1995, 117, 8576.
81. 28. Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. Stille, J.K. Pure Appl. Chem. 1985, 57, 1771. Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1987, 109, 5478. Mitchell, T.N. Synthesis 1992, 803. Farina, V.; Krishnan, B.; Marshall, D.R.; Roth, G.P. J. Org. Chem. 1993, 58, 5434. Farina, V.; Kapadia, S.; Krishnan, B., Wang, C.; Liebeskind, L.S. J. Org. Chem. 1994, 59, 5905. Roth, G.P.; Farina, V.; Liebeskind, L.S.; Peña-Cabrera E. Tetrahedron Lett. 1995, 36, 2191. Morita, D.K.; Stille, J.K.; Norton, J.R. J. Am. Chem. Soc. 1995, 117, 8576.
82. 28. Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. Stille, J.K. Pure Appl. Chem. 1985, 57, 1771. Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1987, 109, 5478. Mitchell, T.N. Synthesis 1992, 803. Farina, V.; Krishnan, B.; Marshall, D.R.; Roth, G.P. J. Org. Chem. 1993, 58, 5434. Farina, V.; Kapadia, S.; Krishnan, B., Wang, C.; Liebeskind, L.S. J. Org. Chem. 1994, 59, 5905. Roth, G.P.; Farina, V.; Liebeskind, L.S.; Peña-Cabrera E. Tetrahedron Lett. 1995, 36, 2191. Morita, D.K.; Stille, J.K.; Norton, J.R. J. Am. Chem. Soc. 1995, 117, 8576.
83. 28. Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. Stille, J.K. Pure Appl. Chem. 1985, 57, 1771. Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1987, 109, 5478. Mitchell, T.N. Synthesis 1992, 803. Farina, V.; Krishnan, B.; Marshall, D.R.; Roth, G.P. J. Org. Chem. 1993, 58, 5434. Farina, V.; Kapadia, S.; Krishnan, B., Wang, C.; Liebeskind, L.S. J. Org. Chem. 1994, 59, 5905. Roth, G.P.; Farina, V.; Liebeskind, L.S.; Peña-Cabrera E. Tetrahedron Lett. 1995, 36, 2191. Morita, D.K.; Stille, J.K.; Norton, J.R. J. Am. Chem. Soc. 1995, 117, 8576.
84. 28. Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. Stille, J.K. Pure Appl. Chem. 1985, 57, 1771. Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1987, 109, 5478. Mitchell, T.N. Synthesis 1992, 803. Farina, V.; Krishnan, B.; Marshall, D.R.; Roth, G.P. J. Org. Chem. 1993, 58, 5434. Farina, V.; Kapadia, S.; Krishnan, B., Wang, C.; Liebeskind, L.S. J. Org. Chem. 1994, 59, 5905. Roth, G.P.; Farina, V.; Liebeskind, L.S.; Peña-Cabrera E. Tetrahedron Lett. 1995, 36, 2191. Morita, D.K.; Stille, J.K.; Norton, J.R. J. Am. Chem. Soc. 1995, 117, 8576.
85. 28. Stille, J.K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. Stille, J.K. Pure Appl. Chem. 1985, 57, 1771. Echavarren, A.M.; Stille, J.K. J. Am. Chem. Soc. 1987, 109, 5478. Mitchell, T.N. Synthesis 1992, 803. Farina, V.; Krishnan, B.; Marshall, D.R.; Roth, G.P. J. Org. Chem. 1993, 58, 5434. Farina, V.; Kapadia, S.; Krishnan, B., Wang, C.; Liebeskind, L.S. J. Org. Chem. 1994, 59, 5905. Roth, G.P.; Farina, V.; Liebeskind, L.S.; Peña-Cabrera E. Tetrahedron Lett. 1995, 36, 2191. Morita, D.K.; Stille, J.K.; Norton, J.R. J. Am. Chem. Soc. 1995, 117, 8576.
86. 29. For a review on the synthetic transformations of vinyl and aryl inflates, see : Ritter, K. Synthesis 1993, 735.
87. 30. Schreier, E. Helv. Chem. Acta 1964, 47, 1529.
88. 31. I.U.P.A.C. nomenclature : see experimental section.
89. 32. Terada, T.; Fujimoto, K.; Nomura, M.; Yamashita, J.-i.; Kobunai, T.; Takeda, S.; Wierzba, K.; Yamada, Y.; Yamaguchi, H. Chem. Pharm. Bull. 1992, 40, 2720.
90. 33. Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585.
91. 1H NMR spectra of cis and trans lactone isomers, see: Brewer, C.F.; Loike, J.D.; Horwitz, S.B.; Sternlicht, H.; Gensler, W.J. J. Med. Chem. 1979, 22, 215.
92. 35. Saulnier, M.G.; LeBoulluec, K.L.; Long B.H.; Vyas, D.M.; Crosswell, A.R.; Doyle, T.W. Bioorg. Med. Chem. Lett. 1992, 2, 1213.
93. 36. Martorell, G., García-Raso, A.; Saá, J.M. Tetrahedron Lett. 1990, 31, 2357. Saá, J.M.; Martorell, G. García-Raso A. J. Org. Chem. 1992, 57, 678.
94. 36. Martorell, G., García-Raso, A.; Saá, J.M. Tetrahedron Lett. 1990, 31, 2357. Saá, J.M.; Martorell, G. García-Raso A. J. Org. Chem. 1992, 57, 678.
95. 37. VanRheenen, V.; Kelly, R.C.; Cha, D.Y. Tetrahedron Lett. 1976, 1973.
96. 38. Pappo, R.; Allen, D.S.; Lemieux, R.U.; Johnson, W.S. J. Org. Chem. 1956, 21, 478.
97. 39. Hirsch, A.; Orphanos, D. J. Heterocyclic Chem. 1965, 2, 206.
98. 40. Kadow, J.F.; Vyas, D.M.; Doyle, T.W. Tetrahedron Lett. 1989, 39, 3299.
99. 41. Prakash, C.; Saleh, S.; Blair, I.A. Tetrahedron Lett. 1989, 30, 19.
100. 42. Baker, R.; Cummings, W.J.; Hayes, J.F.; Kumar, A. J. Chem. Soc., Chem. Commun. 1986, 1237.
101. 43. For a review on fluoride ion as a base in organic chemistry, see : Clark, J.H. Chem. Rev. 1980, 80, 429.
102. 44. Deny, W.B.; Pamidi, C.C.; Gupta, R.S. Anti-Cancer Drug Design 1993, 8, 203.
103. 45. Huning, S.; Wehner, G. Synthesis 1975, 1980.
104. -6.
105. -7 M.
106. 48. Still, W.C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.