Synthesis of azadirachtin: A long but successful journey

Angewandte Chemie - International Edition

Volumn 46, Issue 40, 2007, Pages 7629-7632

  Veitch, Gemma E ^a   Beckmann, Edith ^a   Burke, Brenda J ^a   Boyer, Alistair ^a   Maslen, Sarah L ^a   Ley, Steven V ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Azadirachtin; Claisen rearrangement; Epoxidation; Radical cyclization; Total synthesis

Indexed keywords

CYCLIZATION; EPOXIDATION; GAME THEORY; SYNTHESIS (CHEMICAL);

AZADIRACHTIN; CLAISEN REARRANGEMENT; RADICAL CYCLIZATION;

INSECTICIDES;

AZADIRACHTIN; LIMONOID; MESYLIC ACID DERIVATIVE;

ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; SYNTHESIS;

LIMONINS; MESYLATES; MOLECULAR STRUCTURE;

EID: 35048889990     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200703027     Document Type: Article

References (80)

1. a) P. S. Jones, S. V. Ley, E. D. Morgan, D. Santafianos, The Chemistry of the Neem Tree in Focus on Phytochemical Pesticides, Vol. 1 (Ed.: M. Jacobson), CRC Press, Boca Raton, 1989, pp. 19-45;
2. b) S. V. Ley, A. A. Denholm, A. Wood, Nat. Prod. Rep. 1993, 10, 109-157.
3. a) P. R. Zanno, I. Miura, K. Nakanishi, D. L. Elder, J. Am. Chem. Soc. 1975, 97, 1975-1977;
4. b) C. J. Turner, M. S. Tempesta, R. B. Taylor, M. G. Zagorski, J. S. Termini, D. R. Schroeder, K. Nakanishi, Tetrahedron 1987, 43, 2789-2803.
5. a) W. Kraus, M. Bokel, A. Klenk, H. Poehnl, Tetrahedron Lett. 1985, 26, 6435-6438;
6. b) W. Kraus, M. Bokel, A. Bruhn, R. Cramer, I. Klaiber, A. Klenk, G. Nagl, H. Poehnl, H. Sadlo, B. Volger, Tetrahedron 1987, 43, 2817-2830.
7. a) J. N. Bilton, H. B. Broughton, S. V. Ley, Z. Lidert, E. D. Morgan, H. S. Rzepa, R. N. Sheppard, J. Chem. Soc. Chem. Commun. 1985, 968-971;
8. b) H. B. Broughton, P. S. Jones, S. V. Ley, E. D. Morgan, A. M. Z. Slawin, D. J. Williams, Proc. 3rd Int. Neem Conf. Nairobi 1986, pp. 103-110;
9. c) H. B. Broughton, S. V. Ley, A. M. Z. Slawin, D. J. Williams, J. Chem. Soc. Chem. Commun. 1986, 46-47;
10. d) J. N. Bilton, H. B. Broughton, P. S. Jones, S. V. Ley, Z. Lidert, E. D. Morgan, H. S. Rzepa, R. N. Sheppard, A. M. Z. Slawin, D. J. Williams, Tetrahedron 1987, 43, 2805-2815;
11. e) S. V. Ley, H. Lovell, D. J. Williams, J. Chem. Soc. Chem. Commun. 1992, 1304-1306;
12. f) S. V. Ley, K. Doherty, G. Massiot, J.-M. Nuzillard, Tetrahedron 1994, 50, 12267-12280.
13. H. B. Broughton, S. V. Ley, A. M. Z. Slawin, D. J. Williams, E. D. Morgan, J. Chem. Soc. Chem. Commun. 1986, 46-47.
14. a) For a review see : A. J. Mordue, A. Blackwell, J. Insect Physiol. 1993, 39, 903-924;
15. b) W. M. Blaney, M. S. J. Simmonds, S. V. Ley, J. C. Anderson, P. L. Toogood, Entomol. Exp. Appl. 1990, 55, 149-160;
16. c) M. S. J. Simmonds, W. M. Blaney, S. V. Ley, J. C. Anderson, P. L. Toogood, Entomol. Exp. Appl. 1990, 55, 169-181;
17. d) M. S. J. Simmonds, W. M. Blaney, R. B. Grossman, S. V. Ley, J. Insect Physiol. 1995, 41, 555-564;
18. e) H. Schmutterer, The Neem Tree, VCH, Weinheim, 1995;
19. f) M. S. J. Simmonds, W. M. Blaney, S. V. Ley, J. C. Anderson, R. Banteli, A. A. Denholm, P. C. W. Green, R. B. Grossman, C. Gutteridge, L. Jennens, S. C. Smith, P. L. Toogood, A. Wood, Entomol. Exp. Appl. 1995, 77, 69-80;
20. g) A. J. Nisbet, A. J. Mordue, L. M. Williams, L. Hannah, L. Jennens, S. V. Ley, W. Mordue, Tissue Cell 1996, 28, 725-729;
21. h) A. J. Mordue Luntz, A. J. Nisbet, L. Jennens, S. V. Ley, W. Mordue, A. Juss. Int. Neem Conference Gatton Australia 1996, chap. 22, pp. 247-258;
22. i) A. J. Nisbet, A. J. Mordue, R. B. Grossman, L. Jennens, S. V. Ley, W. Mordue, Arch. Insect Biochem. Physiol. 1997, 34, 461-473;
23. j) A. J. Mordue, M. S. J. Simmonds, S. V. Ley, W. M. Blaney, W. Mordue, M. Nasiruddin, A. J. Nisbet, Pestic. Sci. 1998, 54, 277-284;
24. k) A. Salehzadeh, A. Jabbar, L. Jennens, S. V. Ley, R. S. Annadurai, R. Adams, R. H. C. Strang, Pest Manage. Sci. 2002, 58, 268-276;
25. l) S. C. Robertson, W. Ni, T. S. Dhadialla, S. Tarlochan, A. J. Nisbet, C. McCusker, S. V. Ley, W. Mordue, A. J. Mordue Luntz, Arch. Insect Biochem. Physiol. 2007, 64, 200-208.
26. a) M. G. Brasca, H. B. Broughton, D. Craig, S. V. Ley, A. Abad Somovilla, P. L. Toogood, Tetrahedron Lett. 1988, 29, 1853-1856;
27. b) S. V. Ley, A. Abad Somovilla, H. B. Broughton, D. Craig, A. M. Z. Slawin, P. L. Toogood, D. J. Williams, Tetrahedron 1989, 45, 2143-2164;
28. c) Y. Nishikimi, T. Iimori, M. Sodeoka, M. Shibasaki, J. Org. Chem. 1989, 54, 3354-3359;
29. d) X. Chen, Y. Luo, Q. Zhu, Z. Wang, Chin. Chem. Lett. 1992, 3, 971;
30. e) K. J. Henry, B. Fraser-Reid, J. Org. Chem. 1994, 59, 5128-5129;
31. f) H. Watanabe, T. Watanabe, K. Mori, Tetrahedron 1996, 52, 13939-13950;
32. g) H. Watanabe, T. Watanabe, K. Mori, T. Kitihara, Tetrahedron Lett. 1997, 38, 4429-4432;
33. h) H. Schlesiger, E. Winterfeldt, Chirality 1997, 9, 454-458;
34. i) N. Kanoh, J. Ishihara, A. Murai, Synlett 1997, 737-739;
35. j) J. Ishihara, T. Fukuzaki, A. Murai, Tetrahedron Lett. 1999, 40, 1907-1910;
36. k) J. Ishihara, Y. Yamamoto, N. Kanoh, A. Murai, Tetrahedron Lett. 1999, 40, 4387-4390;
37. l) Y. Yamamoto, J. Ishihara, N. Kanoh, A. Murai, Synthesis 2000, 1894-1906;
38. m) K. C. Nicolaou, M. Follmann, A. J. Roecker, K. W. Hunt, Angew. Chem. 2002, 114, 2207-2210;
39. Angew. Chem. Int. Ed. 2002, 41, 2103-2106;
40. n) K. C. Nicolaou, A. J. Roecker, M. Follmann, R. Baati, Angew. Chem. 2002, 114, 2211-2214;
41. Angew. Chem. Int. Ed. 2002, 41, 2107-2110;
42. o) T. Fukuzaki, S. Kobayashi, T. Hibi, Y. Ikuma, J. Ishihara, N. Kanoh, A. Murai, Org. Lett. 2002, 4, 2877-2880;
43. p) K. C. Nicolaou, A. J. Roecker, H. Monenschein, P. Guntupalli, M. Follmann, Angew. Chem. 2003, 115, 3765-3770;
44. Angew. Chem. Int. Ed. 2003, 42, 3637-3642;
45. q) A. Murai, J. Toxicol. Toxin Rev. 2003, 22, 617-632;
46. r) K. C. Nicolaou, P. K. Sasmal, A. J. Roecker, X. W. Sun, S. Mandal, A. Converso, Angew. Chem. 2005, 117, 3509-3513;
47. Angew. Chem. Int. Ed. 2005, 44, 3443-3447;
48. s) K. C. Nicolaou, P. K. Sasmal, T. V. Koftis, A. Converso, E. Loizidou, F. Kaiser, A. J. Roecker, C. C. Dellios, X. W. Sun, G. Petrovic, Angew. Chem. 2005, 117, 3513-3518;
49. Angew. Chem. Int. Ed. 2005, 44, 3447-3452;
50. t) H. Watanabe, N. Mori, D. Itoh, T. Kitahara, K. Mori, Angew. Chem. 2007, 119, 1534-1538;
51. Angew. Chem. Int. Ed. 2007, 46, 1512-1516.
52. S. V. Ley, Pure Appl. Chem. 2005, 77, 1115-1130.
53. J. H. Butterworth, E. D. Morgan, Chem. Commun. 1968, 23-24.
54. J. N. Bilton, P. S. Jones, S. V. Ley, N. G. Robinson, R. N. Sheppard, Tetrahedron Lett. 1988, 29, 1849-1852;
55. S. V. Ley, J. C. Anderson, W. M. Blaney, E. D. Morgan, R. N. Sheppard, M. S. J. Simmonds, A. M. Z. Slawin, S. C. Smith, D. J. Williams, A. Wood, Tetrahedron 1991, 47, 9231-9246.
56. See preceding communication: G. E. Veitch, E. Beckmann, B. J. Burke, A. Boyer, S. V. Ley, Angew. Chem. 2007, 10.1002/ange.200703028;
57. Angew. Chem. Int. Ed. 2007, 10.1002/anie.200703028.
58. A. A. Denholm, L. Jennens, S. V. Ley, A. Wood, Tetrahedron 1995, 51, 6591-6604.
59. Quarternary Stereocenters (Eds.: J. Christoffers, A. Baro), Wiley-VCH, Weinheim, 2005.
60. J. C. Anderson, S. V. Ley, Tetrahedron Lett. 1990, 31, 431-432;
61. C. E. Gutteridge, PhD Thesis, University of Cambridge, 1996;
62. A. R. Pape, PhD Thesis, University of Cambridge, 1999.
63. H. C. Kolb, S. V. Ley, Tetrahedron Lett. 1991, 32, 6187-6190;
64. H. C. Kolb, S. V. Ley, A. M. Z. Slawin, D. J. Williams, J. Chem. Soc. Perkin Trans. 1 1992, 2735-2762;
65. W.-J. Koot, S. V. Ley, Tetrahedron 1995, 51, 2077-2090.
66. The only difference between the decalin fragment used in our synthesis and that described in the degradation studies is the C1/C3 protecting groups. We were able to convert the benzylidene acetal described therein to its bis-silyl ether. S. V. Ley, P. J. Lovell, S. C. Smith, A. Wood, Tetrahedron Lett. 1991, 32, 6183-6186;
67. S. V. Ley, P. J. Lovell, A. M. Z. Slawin, S. C. Smith, D. J. Williams, A. Wood, Tetrahedron 1993, 49, 1675-1700.
68. M. H. Clausen, M. R. Jorgensen, J. Thorsen, R. Madsen, J. Chem. Soc. Perkin Trans. 1 2001, 543-551.
69. E. Cleator, C. F. McCusker, F. Stelzer, S. V. Ley, Tetrahedron Lett. 2004, 45, 3077-3080.
70. D. R. Mootoo, V. Date, B. Fraser-Reid, J. Am. Chem. Soc. 1988, 110, 2662-2663.
71. S. V. Ley, J. Norman, W. P. Griffith, S. P. Marsden, Synthesis 1994, 639-666.
72. D. H. R. Barton, S. W. McCombie, J. Chem. Soc. Perkin Trans. 1 1975, 1574-1585.
73. We thank E. Cleator, N. Hahn, A. Mattes, and F. Stelzer for these early but important contributions, details of which will follow in a full paper.
74. This route provided a total of 0.8 g of propargylic mesylates 7, which was subsequently coupled with decalin fragment 6.
75. While we do see mixtures of O- and C-alkylation products in experiments with simplified models of both fragments, pleasingly exclusive O-alkylation is observed in the real system, which we believe to be due to fortuitous steric factors.
76. T. Durand-Reville, L. B. Gobbi, B. L. Gray, S. V. Ley, J. S. Scott, Org. Lett. 2002, 4, 3847-3850.
77. S. V. Ley, C. E. Gutteridge, A. R. Pape, C. D. Spilling, C. Zumbrunn, Synlett 1999, 1295-1297;
78. B. D. Sherry, F. D. Toste, J. Am. Chem. Soc. 2004, 126, 15978-15979;
79. 4.
80. P. Brougham, M. S. Cooper, D. A. Cummerson, H. Heaney, N. Thompson, Synthesis 1987, 1015-1017.