Skip to main content
SpringerLink
Log in

Inception and Development of a Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline

  • Chapter
  • First Online:
Stereoselective Desymmetrization Methods in the Assembly of Complex Natural Molecules

Part of the book series: Springer Theses ((Springer Theses))

  • 414 Accesses

Abstract

The total synthesis of terpene alkaloid natural products has received significant attention from the synthetic community in the last half-century. In recent years, however, synthetic interest in these targets has been reignited, in no small part due to the continued discovery of natural molecules bearing deviations from the classical steroid architecture. These findings have challenged the organic chemist toward new innovations in the preparation of these molecules.

Reprinted in part with permission from Sharpe, R. J.; Johnson, J. S. J. Am. Chem. Soc. 2015, 137, 4968, and Sharpe, R. J.; Johnson, J. S. J. Org. Chem. 2015, 80, 9740.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    Partial and total synthetic studies on terpene alkaloids.

References

  1. H. Sings, S. Singh, Alkaloids: Chem Biol 60, 51 (2003)

    CAS  Google Scholar 

  2. T. Miedaner, Geiger. H. H. Toxins 7, 659 (2015). (and references therein)

    Article  CAS  Google Scholar 

  3. P.S. Steyn, R. Vleggar, Progress in the Chemistry of Organic Natural Products (Springer, New York, 1985)

    Google Scholar 

  4. P.G. Mantle, P.B. Mortimer, E.P. White, Res. Vet. Sci. 24, 49 (1977)

    Google Scholar 

  5. M.E. DiMenna, P.B. Mantle, Ibid 24, 347 (1977)

    Google Scholar 

  6. P.G. Mantle, J.B. Day, C.R. Haigh, H.C. Penny, Vet. Rec. 103, 403 (1978)

    Article  CAS  Google Scholar 

  7. R.J. Cole, J.W. Dorner, J.A. Landsen, R.H. Cox, C. Pape, B. Cunfer, S.S. Nicholson, D.M. Bedell, J. Agric. Food Chem. 25, 1197 (1977)

    Article  CAS  Google Scholar 

  8. T. Fehr, W. Acklin, Helv. Chem. Acta 1966, 49 (1907)

    Google Scholar 

  9. R.P. Gysi, Ph.D. Dissertation, Eidgenossiche Technische Hochschule, Zürich, Switzerland, 1973, No. 4990

    Google Scholar 

  10. A. Leutwiler, Dissertation No. 5163, Eidgenossiche Technische Hochschule, Zürich, Switzerland, 1973

    Google Scholar 

  11. S.C. Munday-Finch, A.L. Wilkins, C.O. Miles, Phytochemistry 41, 327 (1996)

    Article  CAS  Google Scholar 

  12. R.J. Cole, J.W. Dorner, J.P. Springer, R.H. Cox, J. Agric. Food Chem. 29, 293 (1981)

    Article  CAS  Google Scholar 

  13. R.T. Gallagher, J. Finer, J. Clardy, A. Leutwiler, F. Weibel, W. Acklin, D. Arigoni, Tetrahedron Lett. 21, 231 (1980). (and references therein)

    Article  Google Scholar 

  14. M. Ogata, J.-Y. Ueda, M. Hoshi, J. Hashimoto, T. Nakashima, K. Anzai, M. Takagi, K. Shin-ya, J. Antibiot. 60, 645 (2007)

    Article  CAS  Google Scholar 

  15. R.J. Cole, J.W. Kirksey, J.M. Wells, Can. J. Microbiol. 20, 1159 (1974)

    Article  CAS  Google Scholar 

  16. J.P. Springer, J. Clardy, J.M. Wells, R.J. Cole, J.W. Kirksey, Tetrahedron Lett. 16, 2531 (1975)

    Article  Google Scholar 

  17. G.F. Bills, R.A. Giacobbe, S.H. Lee, F. Peláez, J.S. Tkacz, Mycol. Res. 96, 977 (1992)

    Article  CAS  Google Scholar 

  18. T. Itabashi, T. Hosoe, D. Wakana, K. Fukushima, K. Takizawa, T. Yaguchi, K. Okada, G.M. Takaki, K. Kawai, J. Nat. Med. 63, 96 (2009)

    Article  CAS  Google Scholar 

  19. E. Brnardic, J.B. Doherty, J. Dorsey, C. Ellwood, M. Fillmore, M. Malaska, K. Nelson, M. Soukri, Preparation of indole diterpene alkaloids as maxi-k channel blockers for the treatment of glaucoma. WIPO 2009/048559 (2009)

    Google Scholar 

  20. M.L. Garcia, M. A. Goetz, G.J. Kaczorowski, O.B. McManus, R.L. Monaghan, W.R. Strohl, J.S. Tkacz, Novel Maxi-K Channel Blockers, Methods of Use and Process for Making the Same. U. S. Patent 0239863, 2005

    Google Scholar 

  21. E. Brnardic, J.B. Doherty, C. Ellwood, M. Fillmore, M. Malaska, Maxi-K channel blockers and methods of use. U. S. Patent 048558 (2009)

    Google Scholar 

  22. J.J. Sheehan, B.L. Benedetti, A.L. Barth, Epilepsia 50, 711 (2009)

    Article  CAS  Google Scholar 

  23. J.P. Springer, J. Clardy, Tetrahedron Lett. 21, 231 (1980)

    Article  CAS  Google Scholar 

  24. J.P. Dorner, R.J. Cole, R.H. Cox, B.M. Cunfer, J. Agric. Food Chem. 1984, 32 (1069)

    Google Scholar 

  25. W. Acklin, F. Weibel, D. Arigoni, Chimia 31, 63 (1977)

    Google Scholar 

  26. A.E. de Jesus, C.P. Gorst-Allman, P.S. Steyn, F.R. van Heerden, R. Vieggaar, P.L. Wessels, W.E. Hull, J. Chem. Soc. Perkin Trans. 1983 (1863)

    Google Scholar 

  27. S. Fueki, T. Tokiwano, H. Toshima, H. Oikawa, Org. Lett. 6, 2697 (2004)

    Article  CAS  Google Scholar 

  28. K. Tagami, C. Liu, A. Minami, M. Noike, T. Isaka, S. Fueki, Y. Schichijo, H. Toshima, K. Gomi, T. Dairi, H. Oikawa, J. Am. Chem. Soc. 135, 1260 (2013)

    Article  CAS  Google Scholar 

  29. A.B.I.I.I. Smith, R. Mewshaw, J. Am. Chem. Soc. 107, 1769 (1985)

    Article  CAS  Google Scholar 

  30. A.B.I.I.I. Smith, T.L. Leenay, Tetrahedron Lett. 29, 2787 (1988)

    Article  CAS  Google Scholar 

  31. A.B.I.I.I. Smith, T.L. Leenay, Tetrahedron Lett. 29, 2791 (1988)

    Article  CAS  Google Scholar 

  32. R.E. Mewshaw, M.D. Taylor, A.B. Smith III, J. Org. Chem. 54, 3449 (1989)

    Article  CAS  Google Scholar 

  33. A.B.I.I.I. Smith, T.L. Leenay, J. Am. Chem. Soc. 111, 5761 (1989)

    Article  CAS  Google Scholar 

  34. A.B.I.I.I. Smith, T. Sunazuka, T.L. Leenay, J. Kingery-Wood, J. Am. Chem. Soc. 112, 8197 (1990)

    Article  CAS  Google Scholar 

  35. A.B.I.I.I. Smith, J. Kingery-Wood, T.L. Leenay, E.G. Nolen, T. Sunazuka, J. Am. Chem. Soc. 114, 1438 (1992)

    Article  CAS  Google Scholar 

  36. A.B.I.I.I. Smith, M. Ohta, W.M. Clark, J.W. Leahy, Tetrahedron Lett. 34, 3033 (1993)

    Article  CAS  Google Scholar 

  37. Y. Zou, J.E. Melvin, S.S. Gonzales, M.J. Spafford, A.B. Smith III, J. Am. Chem. Soc. 137, 7095 (2015)

    Article  CAS  Google Scholar 

  38. S. D. Guile, J.E. Saxton, M. Thornton-Pett, J. Chem. Soc. Perkin Trans. 1 1992 (1763)

    Google Scholar 

  39. J.S. Clark, J. Myatt, L. Roberts, N. Walshe, Synlett 2005, 697–699 (2005)

    Google Scholar 

  40. F. Churruca, M. Fousteris, Y. Ishikawa, M.W. Rekowski, C. Hounsou, T. Surrey, A. Giannis, Org. Lett. 12, 2096 (2010)

    Article  CAS  Google Scholar 

  41. M. Enomoto, S. Kuwahara, J. Org. Chem. 75, 6286 (2010)

    Article  CAS  Google Scholar 

  42. B. Bradshaw, G. Etxebarria-Jardi, J. Bonjoch, J. Am. Chem. Soc. 132, 5966 (2010)

    Article  CAS  Google Scholar 

  43. M. Oikawa, R. Hashimoto, M. Sasaki, Eur. J. Org. Chem. 2011, 538 (2011)

    Google Scholar 

  44. T. Isaka, M. Hasegawa, H. Toshima, Biosci. Biotechnol. Biochem. 75, 2213 (2011)

    Article  CAS  Google Scholar 

  45. M. Adachi, K. Higuchi, N. Thasasa, H. Yamada, T. Nishikawa, Org. Lett. 14, 114 (2012)

    Article  CAS  Google Scholar 

  46. K. Okano, Y. Yoshii, H. Tokuyama, Heterocycles 84, 1325 (2012)

    Article  CAS  Google Scholar 

  47. S. Enomoto, A. Morita, S. Kuwahara, Angew. Chem. Int. Ed. 51, 12833 (2012)

    Article  CAS  Google Scholar 

  48. M. Bian, Z. Wang, X. Xiong, Y. Sun, C. Matera, K.C. Nicolaou, A. Li, J. Am. Chem. Soc. 134, 8078 (2012)

    Article  CAS  Google Scholar 

  49. A.E. Goetz, A.L. Silberstein, M.A. Corsello, N.K. Garg, J. Am. Chem. Soc. 136, 3036 (2014)

    Article  CAS  Google Scholar 

  50. P.G. Gassman, T.J. van Bergen, D.P. Gilbert, B.W. Cue Jr., J. Am. Chem. Soc. 96, 5495 (1974)

    Article  CAS  Google Scholar 

  51. J.T. Malinowski, R.J. Sharpe, J.S. Johnson, Science 340, 180 (2013)

    Article  CAS  Google Scholar 

  52. R.J. Sharpe, J.T. Malinowski, J.S. Johnson, J. Am. Chem. Soc. 135, 17990 (2013)

    Article  CAS  Google Scholar 

  53. Y. Chu, J.B. White, B.A. Duclos, Tetrahedron Lett. 42, 3815 (2001)

    Article  CAS  Google Scholar 

  54. M. Iguchi, M. Niwa, S. Yamamura, J. Chem. Soc. D.: Chem. Commun. 1971, 974 (1971)

    Google Scholar 

  55. I.C. Stewart, T. Ung, A.A. Pletnev, J.M. Berlin, R.H. Grubbs, Y. Schrodi, Org. Lett. 9, 1589 (2007)

    Article  CAS  Google Scholar 

  56. T. Vorfalt, S. Leuhausser, H. Plenio, Angew. Chem. Int. Ed. 48, 5191 (2009)

    Article  CAS  Google Scholar 

  57. J.E. McMurry, M.P. Fleming, K.L. Kees, L.R. Krepski, J. Org. Chem. 43, 3255 (1978)

    Article  CAS  Google Scholar 

  58. A.T. Parsons, J.S. Johnson, J. Am. Chem. Soc. 131, 14202 (2009)

    Article  CAS  Google Scholar 

  59. H. Qian, X. Han, R.A. Widenhoefer, J. Am. Chem. Soc. 126, 9536 (2004)

    Article  CAS  Google Scholar 

  60. R.K. Boeckman Jr., M.R. Reeder, J. Org. Chem. 62, 6456 (1997)

    Article  CAS  Google Scholar 

  61. M.B. Boxer, H. Yamamoto, Org. Lett. 7, 3127 (2005)

    Article  CAS  Google Scholar 

  62. A.T. Parsons, A.G. Smith, A.N. Neel, J.S. Johnson, J. Am. Chem. Soc. 132, 9688 (2010)

    Article  CAS  Google Scholar 

  63. A.G. Smith, M.C. Slade, Org. Lett. 2011, 13 (1996)

    Google Scholar 

  64. S.J. Gharpure, S.R.B. Reddy, Org. Lett. 11, 2519 (2009)

    Article  CAS  Google Scholar 

  65. B. Breit, S.K. Zahn, J. Org. Chem. 66, 4870 (2001)

    Article  CAS  Google Scholar 

  66. J. Germain, P. Deslongchamps, J. Org. Chem. 67, 5269 (2002)

    Article  CAS  Google Scholar 

  67. M.A. Gianturco, P. Friedal, Tetrahedron 19, 2039 (1963)

    Article  CAS  Google Scholar 

  68. H.O. House, In Modern Synthetic Reactions (Benjamin, Menlo Park, 1972), pp. 520–532

    Google Scholar 

  69. J.C. Stowell, In Carbanions in Organic Synthesis (Wiley, New York, 1979), pp. 205–210

    Google Scholar 

  70. A.S. Demir, D.J. Enders, J. Prakt. Chem. 339, 553 (1997)

    Article  CAS  Google Scholar 

  71. H. Watanabe, M. Iwamoto, M. Nakada, J. Org. Chem. 70, 4652 (2005)

    Article  CAS  Google Scholar 

  72. T. Katoh, S. Mizumoto, M. Fudesaka, Y. Nakashima, T. Kajimoto, M. Node, Synlett 2006, 2076 (2006)

    Google Scholar 

  73. T. Katoh, S. Mizumoto, M. Fudesaka, M. Takeo, T. Kajimoto, M. Node, Tetrahedron: Asymmetry 2006, 17, 1655 (2006)

    Google Scholar 

  74. A.D. Becke, J. Chem. Phys. 98, 5648 (1993)

    Article  CAS  Google Scholar 

  75. C.T. Lee, W.T. Yang, R.G. Parr, Phys, Rev. B 37, 785 (1988)

    Google Scholar 

  76. P.C. Hariharanan, J.A. Pople, Theor. Chim. Acta. 28, 213 (1973)

    Article  Google Scholar 

  77. M.M. Franci, W.J. Pietro, W.J. Henre, J.S. Binley, M.S. Gordon, D.J. Frees, J.A. Pople, J. Chem. Phys. 1982, 77, 3654 (1982). See Section 3.5 for more details

    Google Scholar 

  78. W. Zhang, H. Yamamoto, J. Am. Chem. Soc. 129, 286 (2007)

    Article  CAS  Google Scholar 

  79. K.K. Wan, K. Iwasaki, J.C. Umotoy, D.W. Wolan, R.A. Shenvi, Angew. Chem. Int. Ed. 54, 2410 (2015)

    Article  CAS  Google Scholar 

  80. R.H. Shapiro, M.J. Heath, J. Am. Chem. Soc. 89, 5734 (1967)

    Article  CAS  Google Scholar 

  81. R.H. Shapiro, Org. React. (N.Y.), 1975, 23, 405

    Google Scholar 

  82. G. Stork, S.D. Darling, J. Am. Chem. Soc. 82, 1512 (1960)

    Article  CAS  Google Scholar 

  83. G. Stork, P. Rosen, N. Goldman, R.V. Coombs, J. Tsuji, J. Am. Chem. Soc. 87, 275 (1965)

    Article  CAS  Google Scholar 

  84. M. Vilkas, Bull. Soc. Chem. Fr. 1959, 1401 (1959)

    Google Scholar 

  85. G. Stork, M. Kahn, J. Am. Chem. Soc. 107, 500 (1985)

    Article  CAS  Google Scholar 

  86. G. Stork, P.M. Sher, J. Am. Chem. Soc. 108, 303 (1986)

    Article  CAS  Google Scholar 

  87. R.E. Ireland, R.H. Mueller, J. Am. Chem. Soc. 94, 5897 (1972)

    Article  CAS  Google Scholar 

  88. R.E. Ireland, R.H. Mueller, A.K. Willard, J. Am. Chem. Soc. 98, 2868 (1976)

    Article  CAS  Google Scholar 

  89. I. Fleming, R. Henning, H. Plaut, J. Chem. Soc. Chem. Commun. 1984, 29 (1984)

    Google Scholar 

  90. L.V. Desai, K.L. Hull, M.S. Sanford, J. Am. Chem. Soc. 126, 9542 (2004)

    Article  CAS  Google Scholar 

  91. S.R. Neufeldt, M.S. Sanford, Org. Lett. 12, 532 (2010)

    Article  CAS  Google Scholar 

  92. C. Zhu, P. Tang, B. Yu, J. Am. Chem. Soc. 130, 5872 (2008)

    Article  CAS  Google Scholar 

  93. D.A. Siler, J.D. Mighion, E.J. Sorenson, Angew. Chem. Int. Ed. 53, 5332 (2014)

    Article  CAS  Google Scholar 

  94. A. Krasovskiy, F. Kopp, P. Knochel, Angew. Chem. Int. Ed. 45, 497 (2006)

    Article  CAS  Google Scholar 

  95. A. Abad, C. Agullo, M. Arno, L.R. Domingo, R.J. Zaragoza, J. Org. Chem. 1990, 55, 2369 (1990) (and references therein)

    Google Scholar 

  96. D.A. Evans, M. Morrisey, J. Am. Chem. Soc. 106, 3866 (1984)

    Article  CAS  Google Scholar 

  97. D.A. Evans, M. Morrisey, Tetrahedron Lett. 25, 4637 (1984)

    Article  CAS  Google Scholar 

  98. A.F. St. André, H.B. MacPhillamy, J.A. Nelson, A.C. Shabica, C.R. Scholz, J. Am. Chem. Soc. 1952, 74, 5506 (1952)

    Google Scholar 

  99. R.B. Gabbard, A. Segaloff, Steroids 41, 791 (1983)

    Article  CAS  Google Scholar 

  100. M. Haddad, J.C. Blazejewski, C. Wakselman, V. Dorai, I. Duc, Eur. J. Med. Chem. 29, 627 (1994)

    Article  CAS  Google Scholar 

  101. V.A. Khripach, V.N. Zhabinskii, G.P. Fando, A.I. Kuchto, A.S. Lyakhov, A.A. Govorova, M.B. Groen, J. Van Der Louw, A. De Groot, Steroids 69, 495 (2004)

    Article  CAS  Google Scholar 

  102. B. Breit, S.K. Zahn, J. Org. Chem. 66, 4870 (2001)

    Article  CAS  Google Scholar 

  103. S.-K. Xiang, B. Zhang, L.-H. Zhang, Y. Cui, N. Jiao, Chem. Commun. 47, 8097 (2011)

    Article  CAS  Google Scholar 

  104. H.-B. Zhang, L. Liu, Y.-L. Liu, Y.-J. Chen, J. Wang, D. Wang, Synth. Commun. 37, 173 (2005)

    Article  Google Scholar 

  105. M. Westermaier, H. Mayr, Org. Lett. 8, 4791 (2006)

    Article  CAS  Google Scholar 

  106. H.E. Zimmerman, P. Wang, J. Org. Chem. 67, 9216 (2002)

    Article  CAS  Google Scholar 

  107. F.F. Van Goor, W.L. Burton, Compositions for treatment of cystic fibrosis and other chronic diseases. U.S. Patent 61254180 (2011)

    Google Scholar 

  108. E. Nyfeler, P. Renaud, Org. Lett. 10, 985 (2008)

    Article  CAS  Google Scholar 

  109. C.H. Archer, N.R. Thomas, D. Gani, Tetrahedron Asymm. 4, 1141 (1993)

    Article  CAS  Google Scholar 

  110. F. Hettche, R.W. Hoffmann, New J. Chem. 27, 172 (2003)

    Article  CAS  Google Scholar 

  111. M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03, revision D.01 (Gaussian Inc, Wallingford, CT, 2004)

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Advanced Research Chemist, Eastman Chemical Company, Johnson City, TN, USA

    Robert J. Sharpe

Authors
  1. Robert J. Sharpe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert J. Sharpe .

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Sharpe, R.J. (2016). Inception and Development of a Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline. In: Stereoselective Desymmetrization Methods in the Assembly of Complex Natural Molecules. Springer Theses. Springer, Cham. https://doi.org/10.1007/978-3-319-39025-3_3

Download citation

Publish with us

Policies and ethics

Search

Navigation