Chemoenzymatic and ring E-molecular approach to the (-)-podophyllotoxin skeleton. Synthesis of 3',4',5'-tridemethoxy-(-)-podophyllotoxin

Journal of the American Chemical Society

Volumn 118, Issue 39, 1996, Pages 9426-9427

  Berkowitz, David B ^a   Maeng, Jun Ho ^a   Dantzig, Anne H ^b   Shepard, Robert L ^b   Norman, Bryan H ^b  

^a UNIVERSITY OF NEBRASKA LINCOLN   (United States)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PODOPHYLLOTOXIN DERIVATIVE;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029904857     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja961489s     Document Type: Article

References (47)

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2. (a) Robinson, M. J.; Osherhoff, N. Biochemistry 1991, 30, 1807-1813.
3. (b) Chen, G. L.; Yang, L.; Rowe, T. C.; Halligan, B. D.; Tewey, K. M.; Liu, L. F. J. Biol. Chem. 1984, 259, 13560-13566 and references therein.
4. It has been suggested thai a free 4′-OH is essential for DNA breakage activity: (a) Long, B. H.; Musial, S. T.; Brattain, M. G. Biochemistry 1984, 23, 1183-1188. (b) Loike, J. D.; Horwitz, S. B. Biochemistry 1976, 15, 5443-5448. However, a related, "ring E"-deoxygenated lignan displays potent topoisomerase II inhibition activity: (c) Kamal, A.; Atchinson, K.; Daneshtalab, M.; Micetich, R. G. Anti-Cancer Drug Des. 1995, 10, 545-554.
5. It has been suggested thai a free 4′-OH is essential for DNA breakage activity: (a) Long, B. H.; Musial, S. T.; Brattain, M. G. Biochemistry 1984, 23, 1183-1188. (b) Loike, J. D.; Horwitz, S. B. Biochemistry 1976, 15, 5443-5448. However, a related, "ring E"-deoxygenated lignan displays potent topoisomerase II inhibition activity: (c) Kamal, A.; Atchinson, K.; Daneshtalab, M.; Micetich, R. G. Anti-Cancer Drug Des. 1995, 10, 545-554.
6. It has been suggested thai a free 4′-OH is essential for DNA breakage activity: (a) Long, B. H.; Musial, S. T.; Brattain, M. G. Biochemistry 1984, 23, 1183-1188. (b) Loike, J. D.; Horwitz, S. B. Biochemistry 1976, 15, 5443-5448. However, a related, "ring E"-deoxygenated lignan displays potent topoisomerase II inhibition activity: (c) Kamal, A.; Atchinson, K.; Daneshtalab, M.; Micetich, R. G. Anti-Cancer Drug Des. 1995, 10, 545-554.
7. (a) Sinha, B. K.; Eliot, H. M.; Kalayanaraman, B. FEBS Lett. 1988, 227, 240-244.
8. (b) Haim, N.; Nemec, J.; Roman, J.; Sinha, B. K. Biochem. Pharm. 1987, 36, 527-536.
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10. (d) Van Maanen, J. M. S.; de Vries, J.; Pappie, D.; van der Akker, E.; Vincent, M.; Lafleur, M.; Retel, J.; van der Greef, J.; Pinedo, H. M. Cancer Res. 1987, 47, 4658-4662.
11. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
12. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
13. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
14. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
15. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
16. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
17. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
18. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
19. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
20. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
21. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
22. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
23. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
24. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
25. For a review of synthetic approaches to the Podophyllum lignans. see: (a) Ward, R. S. Synthesis 1992, 719-730. For syntheses of (±)-podophyllotoxin, see: (b) Gensler, W. J.; Gastonis, C. G. J. Org. Chem. 1966, 31, 4004-4008. (c) Kende, A. S.; Liebeskind, L. S.; Mills, J. E.; Rutledge, P. S.; Curran, D. P. J. Am. Chem. Soc. 1977, 99, 7082-7083. (d) Murphy, W. S.; Wattanasin, S. J. Chem. Soc., Chem. Commun. 1980, 262-263. (e) Kende, A. S.; King, M. L.; Curran, D. P. J. Org. Chem. 1981, 46, 2826-2828. (f) Rajapaksa, D.; Rodrigo, R. J. Am. Chem. Soc. 1981, 103, 6208-6209. (g) Jung, M. E.; Lam, P. Y.; Mansuri, M. M.; Speltz, L. M. J. Org. Chem. 1985, 50, 1087-1105. (h) Jung, M. E.; Lowen, G. T. Tetrahedron Lett. 1986, 27, 5319-5322. (i) Van der Eycken, J.; De Clerq, P.; Vandewalle, M. Tetrahedron Lett. 1985, 26, 3871-3874. (j) Macdonald, D. I.; Durst, T. J. Org. Chem. 1986, 51, 4749-4750. (k) Vyas, D. M.; Skonezny, P. M.; Jenks, T. A.; Doyle, T. W. Tetrahedron Lett. 1986, 27, 3099-3102. (l) Kaneko, T.; Wong, H. Tetrahedron Lett. 1987, 28, 517-520. (m) Peterson, J. R.; Hoang, D. D.; Rogers, R. D. Synthesis 1991, 275-277. (n) Jones, D. W.; Thompson, A. M. J. Chem. Soc., Chem. Commun. 1987, 1797-1798. (o) Kraus, G. A.; Wu, Y. J. Org. Chem. 1992, 57, 2922-2925.
26. (a) Andrews, R. C.; Teague, S. J.; Meyers, A. I. J. Am. Chem. Soc. 1988, 110, 7854-7858.
27. (b) Bush, E. J.; Jones, D. W. J. Chem. Soc., Perkin Trans. 1 1996, 151-155.
28. Two formal syntheses of 1 have also been reported. (a) (-) Epipodophyllotoxin: Van Speybroeck, R.; Guo, H.; Van der Eycken, J.; Vandewalle, M. Tetrahedron 1991, 47, 4675-4682. (b) (-)-Neopodophyllotoxin: Charlton, J. L.; Koh, K. J. Org. Chem. 1992, 57, 1514-1516.
29. Two formal syntheses of 1 have also been reported. (a) (-) Epipodophyllotoxin: Van Speybroeck, R.; Guo, H.; Van der Eycken, J.; Vandewalle, M. Tetrahedron 1991, 47, 4675-4682. (b) (-)-Neopodophyllotoxin: Charlton, J. L.; Koh, K. J. Org. Chem. 1992, 57, 1514-1516.
30. For recent reviews of chemoenzymatic natural product synthesis, see: (a) Johnson, C. R. Tetrahedron 1996, 52, 3769-3826. (b) Mori, K. Synlett 1995, 1097-1109.
31. For recent reviews of chemoenzymatic natural product synthesis, see: (a) Johnson, C. R. Tetrahedron 1996, 52, 3769-3826. (b) Mori, K. Synlett 1995, 1097-1109.
32. 2-H: dd, J = 11, 14 Hz) providing epiisopodophyllotoxins: (a) Kutney, J. P.; Du, X.; Naidu, R.; Stoynov, N. M.; Takemoto, M. Heterocycles 1996, 42, 479-484. (b) Kutney, J. P.; Chen, Y. P.; Gao, S.; Hewitt, G. M.; Kuri-Brena, F.; Milanova, R. K.; Stoynov, N. M. Ibid. 1993, 36, 13-20.
33. 2-H: dd, J = 11, 14 Hz) providing epiisopodophyllotoxins: (a) Kutney, J. P.; Du, X.; Naidu, R.; Stoynov, N. M.; Takemoto, M. Heterocycles 1996, 42, 479-484. (b) Kutney, J. P.; Chen, Y. P.; Gao, S.; Hewitt, G. M.; Kuri-Brena, F.; Milanova, R. K.; Stoynov, N. M. Ibid. 1993, 36, 13-20.
34. Bromination of piperonal proceeds in 84% yield: (a) Conrad, P. C.; Kwiatkowski, P. L.; Fuchs, P. L. J. Org. Chem. 1987, 52, 586-591. Acetalization provides 8 in 96% yield: (b) Keay, B. A.; Plaumann, H. P.; Rajapaksa, D., Rodrigo, R. Can. J. Chem. 1983, 61, 1987-1995.
35. Bromination of piperonal proceeds in 84% yield: (a) Conrad, P. C.; Kwiatkowski, P. L.; Fuchs, P. L. J. Org. Chem. 1987, 52, 586-591. Acetalization provides 8 in 96% yield: (b) Keay, B. A.; Plaumann, H. P.; Rajapaksa, D., Rodrigo, R. Can. J. Chem. 1983, 61, 1987-1995.
36. For a review of the use of isobenzofurans in natural product synthesis, see: Rodrigo, R. Tetrahedron 1988, 44, 2093-2135.
37. 13 For details, see: Berkowitz, D. B.; Maeng, J.-H. Tetrahedron: Asymmetry 1996, 7, 1577-1580.
38. Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34, 2543-2549.
39. Keay, B. A.; Rajapaksa, D.; Rodrigo, R. Can. J. Chem. 1984, 62, 1093-1098.
40. (a) Hanessian, S.; Sumi, K. Synthesis 1991, 1083-1089.
41. (b) Hanessian, S.; Thavonekham, B.; DeHoff, B. J. Org. Chem. 1989, 54, 5831-5833.
42. (c) Dorigo, A. E.; Morokuma, K. J. Am. Chem. Soc. 1989, 111, 6524-6536.
43. For an early articulation of this concept, see: Zimmerman, H. E. J. Org. Chem. 1955, 20, 549-557.
44. Kim, S.; Kee, I. S.; Park, Y. H.; Park, J. H. Synlett 1991, 183-184.
45. For a recent review, see: Bellamy, W. T. Annu. Rev. Pharmacol. Toxicol. 1996, 36, 161-183.
46. (a) Beck, W. T.; Mueller, M. J.; Tanzer, L. R. Cancer Res. 1979, 39, 2070-2076.
47. (b) Denizot, F.; Lang, R. J. Immunol. Methods 1989, 89, 271-277.