Total syntheses of pumiliotoxin A and allopumiliotoxin alkaloids. Interplay of pharmacologically active natural products and new synthetic methods and strategies

Chemical Reviews

Volumn 96, Issue 1, 1996, Pages 505-522

  Franklin, Alison S ^a   Overman, Larry E ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001098602     PISSN: 00092665     EISSN: None     Source Type: Journal    
DOI: 10.1021/cr950021p     Document Type: Article

References (122)

1. For a brief discussion of several early seminal total syntheses, see: Fleming, I. Selected Organic Syntheses; Wiley: New York, 1973.
2. For an illuminating brief discussion of the evolution of synthesis planning during this century see: Corey, E. J.; Cheng, X.-M. The Logic of Chemical Synthesis; Wiley: New York, 1989; pp 3-6.
3. Woodward, R. B.; Sondheimer, F.; Taub, D. J. Am. Chem. Soc. 1951, 73, 4057.
4. Woodward, R. B.; Cava, M. P.; Ollis, W. D.; Hunger, A.; Daeniker, H. U.; Schenker, K. J. Am. Chem. Soc. 1954, 76, 4749.
5. Woodward, R. B.; Bader, F. E.; Bickel, H.; Frey, A. J.; Kierstead, R. W. Tetrahedron 1958, 2, 1.
6. Many of these syntheses are briefly outlined in: Anand, N.; Bindra, J. S.; Ranganathan, S. Art in Organic Synthesis; Holden-Day: San Francisco; 1970.
7. (a) Sheehan, J. C.; Izzo, P. T. J. Am. Chem. Soc. 1948, 70, 1985.
8. (b) Sheehan, J. C.; Bose, A. K. J. Am. Chem. Soc. 1950, 72, 5158.
9. (c) Sheehan, J. C.; Hess, G. P. J. Am. Chem. Soc. 1955, 77, 1067.
10. (a) Sheehan, J. C.; Henery-Logan, K. R. J. Am. Chem. Soc. 1957, 79, 1262.
11. (b) Sheehan, J. C.; Henery-Logan, K. R. J. Am. Chem. Soc. 1959, 81, 3089.
12. For a recent solution and references to earlier accomplishments, see: Lipshutz, B. H.; Wood, M. R. J. Am. Chem. Soc. 1994, 116, 11689.
13. For a recent synthesis and references to earlier work, see: Evans, D. A.; Ratz, A. M.; Huff, B. E.; Sheppard, G. S. J. Am. Chem. Soc. 1995, 117, 3448.
14. 12,13
15. See, inter alia: (a) Woodward, R. B. Pure Appl. Chem. 1973, 33, 145. (b) Eschenmoser, A.; Wintner, C. E. Science 1977, 196, 1410.
16. See, inter alia: (a) Woodward, R. B. Pure Appl. Chem. 1973, 33, 145. (b) Eschenmoser, A.; Wintner, C. E. Science 1977, 196, 1410.
17. Armstrong, R. W.; Beau, J. -M.; Cheon, S. H.; Christ, W. J.; Fujikoa, H.; Ham, W. -H.; Hawkins, L. D.; Jin, H.; Kang, S. H.; Kishi, Y.; Martinelli, M. J.; McWhorter, W. W., Jr.; Mizuno, M.; Nakata, M.; Stutz, A. E.; Talamas, F. X.; Taniguchi, M.; Tino, J. A.; Ueda, K.; Uenishi, J.; White, J. B.; Yonaga, M. J. Am. Chem. Soc. 1989, 111, 7525.
18. For recent reviews, see: (a) Daly, J. W.; Garraffo, H. M.; Spande, T. F. Alkaloids 1993, 43, 185. (b) Daly, J. W.; Spande, T. F. In Alkaloids: Chemical and Biological Perspectives; Pelletier, S. W., Ed.; Wiley: New York, 1986; Vol. 4, Chapter 1.
19. For recent reviews, see: (a) Daly, J. W.; Garraffo, H. M.; Spande, T. F. Alkaloids 1993, 43, 185. (b) Daly, J. W.; Spande, T. F. In Alkaloids: Chemical and Biological Perspectives; Pelletier, S. W., Ed.; Wiley: New York, 1986; Vol. 4, Chapter 1.
20. For a recent discussion of the possibility that the skin alkaloids of dendrobatid frogs may have a dietary origin, see: Daly, J. W.; Secunda, S. I.; Garraffo, H. M.; Spande, T. F.; Wisnieski, A.; Cover, J. F., Jr. Toxicon 1994, 32, 657.
21. (a) Garraffo, H. M.; Caceres, J.; Daly, J. W.; Spande, T. F.; Andriamaharavo, N. R.; Andriantsiferana, M. J. Nat. Prod. 1993, 56, 1016.
22. (b) Garraffo, H. M.; Spande, T. F.; Daly, J. W.; Baldessari, A.; Gros, E. G. J. Nat. Prod. 1993, 56, 357.
23. Daly, J. W.; Myers, C. W. Science (Washington, D. C.) 1967, 156, 970.
24. Daly, J. W.; Tokuyama, T.; Fujiwara, T.; Highet, R. J.; Karle, I. L. J. Am. Chem. Soc. 1980, 102, 830.
25. Tokuyama, T.; Shimada, K.; Uemura, M.; Daly, J. W. Tetrahedron Lett. 1982, 23, 2121.
26. Overman, L. E.; McCready, R. J. Tetrahedron Lett. 1982, 23, 2355.
27. Overman, L. E.; Bell, K. L.; Ito, F. J. Am. Chem. Soc. 1984, 104, 4192.
28. For reviews of the pharmacology of pumiliotoxin A and allopumiliotoxin alkaloids, see reference 14.
29. Gusovsky, F.; Padgett, W. L.; Creveling, C. R.; Daly, J. W. Mol. Pharmacol. 1992, 42, 1104 and references cited therein.
30. (a) Daly, J. W.; McNeal, E. T.; Overman, L. E.; Ellison, D. H. J. Med. Chem. 1985, 28, 482.
31. (b) Daly, J. W.; McNeal, E. T.; Gusovsky, F.; Ito, F.; Overman, L. E. J. Med. Chem. 1988, 31, 477.
32. (c) Daly, J. W.; Gusovsky, F.; McNeal, E. T.; Secunda, S.; Bell, M.; Creveling, C. R.; Nishizawa, Y.; Overman, L. E.; Sharp, M. J.; Rossignol, D. P. Biochem. Pharmacol. 1990, 40, 315.
33. (d) Siegl, P. K. S.; Overman, L. E. Abstracts International Union of Physiological Sciences, Vancouver, Canada, July 1986.
34. Standard abbreviations employed are defined in J. Org. Chem. 1994, 59, 7A.
35. For recent reviews of alkene synthesis, see: (a) Inoue, S.; Honda, K. J. Synth. Org. Chem. Jpn. 1993, 51, 894. (b) Larock, R. C. In Advances in Metal-Organic Chemistry; JAI: Greenwich, 1994; Vol. 3, pp 97-224.
36. For recent reviews of alkene synthesis, see: (a) Inoue, S.; Honda, K. J. Synth. Org. Chem. Jpn. 1993, 51, 894. (b) Larock, R. C. In Advances in Metal-Organic Chemistry; JAI: Greenwich, 1994; Vol. 3, pp 97-224.
37. At the time research in the pumiliotoxin A area began, the difficulty in controlling exocyclic alkene stereochemistry was apparent: (a) Ashcroft, W. R.; Joule, J. A. Tetrahedron Lett. 1980, 21, 2341. (b) Nicolaou, K. C.; Claremon, D. A.; Barnette, W. E. J. Am. Chem. Soc. 1980, 102, 6611.
38. At the time research in the pumiliotoxin A area began, the difficulty in controlling exocyclic alkene stereochemistry was apparent: (a) Ashcroft, W. R.; Joule, J. A. Tetrahedron Lett. 1980, 21, 2341. (b) Nicolaou, K. C.; Claremon, D. A.; Barnette, W. E. J. Am. Chem. Soc. 1980, 102, 6611.
39. For the first unambiguous report, see: Koenig, K. E.; Weber, W. P. J. Am. Chem. Soc. 1973, 95, 3416.
40. Colvin, E. W. Silicon Reagents in Organic Synthesis; Academic: London, 1988.
41. For a review of vinylsilane-terminated cyclization reactions, see: Blumenkopf, T. A.; Overman, L. E. Chem. Rev. 1986, 86, 857.
42. For a review of iminium ion-initiated cyclizations, see: Overman, L. E.; Ricca, D. J. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergammon: Oxford, 1991; Vol. 2, Chapter 4.4.
43. Overman, L. E.; Bell, K. L. J. Am. Chem. Soc. 1981, 103, 1851.
44. Overman, L. E.; Lin, N. -H. J. Org. Chem. 1985, 50, 3669.
45. Overman, L. E.; McCready, R. J. Tetrahedron Lett. 1982, 23, 4887.
46. Midland, M. M.; McDowell, D. C.; Hatch, R. L.; Tramontano, A. J. Am. Chem. Soc. 1980, 102, 867.
47. (a) Pirkel, W. H.; Hauske, J. R. J. Org. Chem. 1977, 42, 1839.
48. (b) Rinaldi, P. L.; Levy, G. C. J. Org. Chem. 1980, 45, 4348.
49. (c) Pirkle, W. H.; Hauske, J. R. J. Org. Chem. 1977, 42, 2781.
50. Macdonald, T. L.; Reagan, D. R.; Brinkmeyer, R. S. J. Org. Chem. 1980, 45, 4740.
51. (a) Eisch, J. J.; Foxton, M. W. J. Org. Chem. 1971, 36, 3520.
52. (b) Eisch, J. J.; Damasevitz, G. A. J. Org. Chem. 1976, 41, 2214.
53. Ylide 35 has been employed in several total syntheses of pumiliotoxin A and allopumiliotoxin A alkaloids and an improved synthesis of this reagent has recently been developed: L. Robinson and M. Rabinowitz, unpublished research at UCI, manuscript in preparation.
54. Garraffo, H. M.; Edwards, M. W.; Spande, T. F.; Daly, J. W.; Overman, L. E.; Severini, C.; Erspamer, V. Tetrahedron 1988, 44, 6795.
55. Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.; Ikeda, M.; Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 6237.
56. Ireland, R. E.; Mueller, R. H.; Willard, A. K. J. Am. Chem. Soc. 1976, 98, 2868.
57. Patai, S. Chemistry of the Carbon-Carbon Triple Bond; Wiley: New York, 1978.
58. (a) Fried, J.; Lin, C.-H.; Ford, S. H. Tetrahedron Lett. 1969, 1379.
59. (b) Fried, J.; Lin, C. H.; Sih, J. C.; Dalven, P.; Cooper, G. F. J. Am. Chem. Soc. 1972, 94, 4342.
60. Sharp, M. J. Ph. D. Dissertation, University of California, Irvine, 1991.
61. Simple alkynes do react with the much more reactive N-acyliminium electrophiles: Dijkink, J.; Schoemaker, H. E.; Speckamp, W. N. Tetrahedron Lett. 1975, 4043.
62. Overman, L. E.; Sharp, M. J. J. Am. Chem. Soc. 1988, 110, 612.
63. (a) Arnold, H.; Overman, L. E.; Sharp, M. J.; Witschel, M. C. Org. Syn. 1991, 70, 111.
64. (b) Overman, L. E.; Sarkar, A. K. Tetrahedron Lett. 1992, 33, 4103.
65. (c) Overman, L. E.; Rodriguez-Campos, I. M. Synlett 1992, 995.
66. Overman, L. E.; Sharp, M. J. Tetrahedron Lett. 1988, 29, 901.
67. Overman, L. E.; Robinson, L. A.; Zablocki, J. J. Am. Chem. Soc. 1992, 114, 368.
68. Bargar, T. M.; Lett, R. M.; Johnson, P. L.; Hunter, J. E.; Chang, C. P.; Pernich, D. J.; Sabol, M. R.; Dick, M. R. J. Agric. Food Chem. 1995, 43, 1044.
69. Evans, D. A.; Bender, S. L.; Morris, J. J. Am. Chem. Soc. 1988, 110, 2506.
70. (a) Overman, L. E.; Goldstein, S. W. J. Am. Chem. Soc. 1984, 106, 5360.
71. (b) Goldstein, S. W.; Overman, L. E.; Rabinowitz, M. H. J. Org. Chem. 1992, 57, 1179.
72. Trost, B. M.; Scanlan, T. S. J. Am. Chem. Soc. 1989, 111, 4988.
73. Aoyagi, S.; Wang, T.-C.; Kibayashi, C. J. Am. Chem. Soc. 1993, 115, 11393.
74. Lett, R. M.; Overman, L. E.; Zablocki, J. Tetrahedron Lett. 1988, 29, 6541.
75. (a) Tabusa, F.; Yamada, T.; Suzuki, K.; Mukaiyama, T. Chem. Lett. 1984, 405.
76. (b) Krause, N.; Seebach, D. Chem. Ber. 1987, 120, 1845.
77. Mead, K. T. Tetrahedron Lett. 1987, 28, 1019.
78. Narahashi, T. Trends Pharmacol. Sci. 1992, 13, 236.
79. 51 and has been observed independently in our laboratories by Dr. Y. Bessard.
80. For an earlier example of this Mannich variant, see: Oppolzer, W.; Hauth, H.; Pfaffli, P.; Wegner, R. Helv. Chim. Acta 1977, 60, 1801.
81. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982, 104, 1737.
82. (a) Evans, D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc. 1988, 110, 3560.
83. (b) Saksena, A. K.; Mangiaracina, P. Tetrahedron Lett. 1983, 24, 273.
84. (c) Nutaitis, C. F.; Gribble, G. W. Tetrahedron Lett. 1983, 24, 4287.
85. Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226.
86. Tokuyama, T.; Daly, J. W.; Highet, R. J. Tetrahedron 1984, 40, 1183.
87. Fox, D. N. A.; Lathbury, D.; Mahon, M. F.; Molloy, K. C.; Gallagher, T. J. Am. Chem. Soc. 1991, 113, 2652.
88. For reviews relating to electrophilic additions to allenes, see: (a) Jacobs, T. L. In The Chemistry of Allenes; Landor, S. R., Ed.; Academic: London, 1982; Vol 2, pp 417-510. (b) Smadja, W. Chem. Rev. 1983, 83, 263.
89. For reviews relating to electrophilic additions to allenes, see: (a) Jacobs, T. L. In The Chemistry of Allenes; Landor, S. R., Ed.; Academic: London, 1982; Vol 2, pp 417-510. (b) Smadja, W. Chem. Rev. 1983, 83, 263.
90. Allenic amine 104 was prepared in four steps from lithium acetylide-ethylene diamine complex, see: (a) Coates, R. M.; Senter, P. D.; Baker, W. R. J. Org. Chem. 1982, 47, 3597. (b) Fox, D. N. A.; Gallagher, T. Tetrahedron 1990, 46, 4697.
91. Allenic amine 104 was prepared in four steps from lithium acetylide-ethylene diamine complex, see: (a) Coates, R. M.; Senter, P. D.; Baker, W. R. J. Org. Chem. 1982, 47, 3597. (b) Fox, D. N. A.; Gallagher, T. Tetrahedron 1990, 46, 4697.
92. Alper, H.; Hartstock, F. W.; Despeyroux, B. J. Chem. Soc., Chem. Commun. 1984, 905.
93. 71
94. (a) Honda, T.; Hoshi, M.; Tsubuki, M. Heterocycles 1992, 34, 1515.
95. (b) Honda, T.; Hoshi, M.; Kanai, K.; Tsubuki, M. J. Chem. Soc., Perkin Trans. 1 1994, 2091.
96. Corey, E. J.; Andersen, N. H.; Carlson, R. M.; Paust, J.; Vedejs, E.; Vlattas, I.; Winter, R. E. K. J. Am. Chem. Soc. 1968, 90, 3245.
97. Bouffard, F. A.; Johnston, D. B. R.; Christensen, B. G. J. Org. Chem. 1980, 45, 1130.
98. Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1980, 102, 4743.
99. Classically, 6-endo cyclization is an unfavorable reaction pathway, see: Baldwin, J. E.; Cutting J.; Dupont, W.; Kruse, L.; Silberman, L.; Thomas, R. C. J. Chem. Soc., Chem. Commun. 1976, 736.
100. Toyoshima, K.; Okuyama, T.; Takayuki, F. J. Org. Chem. 1978, 43, 2789.
101. The yield cannot be specified precisely, since the yields for several steps are not reported in this preliminary account.
102. (a) Takai, K.; Kimura, K.; Kuroda, T.; Hiyama, T.; Nozaki, H. Tetrahedron Lett. 1983, 24, 5281.
103. (b) Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto, K.; Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048.
104. (c) Jin, H.; Uenishi, J.; Christ, W. J.; Kishi, Y. J. Am. Chem. Soc. 1986, 108, 5644.
105. (a) Aoyagi, S.; Wang, T. -C.; Kibayashi, C. J. Am. Chem. Soc. 1992, 114, 10653.
106. (b) Kibayashi, C. Pure Appl. Chem. 1994, 66, 2079.
107. Takano, S.; Samizu, K.; Sugihara, K.; Ogasawara, T. J. Chem. Soc., Chem. Commun. 1989, 1344.
108. Servi, S. J. Org. Chem. 1985, 50, 5865.
109. Wang, Z.-N.; Zhou, W. -S. Tetrahedron 1987, 43, 2935.
110. Daly, J. W.; Secunda, S. I.; Gorrafib, H. M.; Spande, T. F.; Wisnieski, A.; Nishihira, C.; Cover, J. F., Jr. Toxicon 1992, 30, 887.
111. Chang, C. P.; Dripps, J. E., personal communication to L. Overman, March 12, 1987.
112. M. Rabinowitz and Y. Bessard, unpublished research at UCI, manuscript in preparation.
113. For a recent review of allylic conformational effects, see: Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1992, 31, 1124.
114. At this point in time, the more recently developed Mannich cyclization chemistry of alkynes has found less application. The use of this chemistry to prepare alkylidene benzotalquinolizidines has been described: Guiles, J. W.; Meyers, A. I. J. Org. Chem. 1991, 56, 6873.
115. (a) Overman, L. E.; Robichaud, A. J. J. Am. Chem. Soc. 1989, 111, 300.
116. (b) Overman, L. E.; Malone, T. C. J. Org. Chem. 1982, 47, 5297.
117. Overman, L. E.; Burk, R. M. Tetrahedron Lett. 1984, 25, 5739.
118. Overman, L. E.; Malone, T. C.; Meier, G. P. J. Am. Chem. Soc. 1983, 105, 6993.
119. Flann, C. J.; Overman, L. E. J. Am. Chem. Soc. 1987, 109, 6115.
120. 94 were also disclosed.
121. Burke, S. D.; Murtiashaw, C. W.; Dike, M. S.; Smith Strickland, S. M.; Saunders, J. O. J. Org. Chem. 1981, 46, 2400.
122. Trost, B. M.; Murayama, E. J. Am. Chem. Soc. 1981, 103, 6529.