Synthesis of natural products from the Indian neem tree Azadirachta indica

Organic Letters

Volumn 10, Issue 4, 2008, Pages 569-572

  Veitch, Gemma E ^a   Pinto, Andrea ^a   Boyer, Alistair ^a   Beckmann, Edith ^a   Anderson, James C ^b   Ley, Steven V ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b UNIVERSITY OF NOTTINGHAM   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AZADIRACHTIN; BIOLOGICAL PRODUCT; LIMONOID;

ARTICLE; AZADIRACHTA INDICA; CHEMICAL STRUCTURE; CHEMISTRY; INDIA; SYNTHESIS;

AZADIRACHTA; BIOLOGICAL PRODUCTS; INDIA; LIMONINS; MOLECULAR STRUCTURE;

EID: 39749134708     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol7027898     Document Type: Article

References (27)

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2. Schmutterer, H. The Neem Tree; Wiley-VCH: Weinheim, 1995.
3. Extracts from the leaves, fruits, and seeds have all been used in crop protection; see ref 2.
4. Butterworth, J. H.; Morgan, E. D. J. Chem. Soc, Chem. Commun. 1968, 23-24.
5. Schmutterer, H.; Rembold, H. Angew. Entomol. 1980, 89, 179-188.
6. Turner, C. J.; Tempesta, M. S.; Taylor, R. B.; Zagorski, M. G.; Termini, J. S.; Schroeder, D. R.; Nakanishi, K. Tetrahedron 1987, 43, 27892803.
7. Bilton, J. N.; Broughton, H. B.; Jones, P. S.; Ley, S. V.; Lidert, Z.; Morgan, E. D.; Rzepa, H. S.; Sheppard, R. N.; Slawin, A. M. Z.; Williams, D. J. Tetrahedron 1987, 43, 2805-2815.
8. Kraus, W.; Bokel, M.; Brunn, A.; Cramer, R.; Klaiber, I.; Klenk, A.; Nagl, G.; Pohnl, H.; Sadlo, H.; Vogler, B. Tetrahedron 1987,43, 28172830.
9. Veitch, G. E.; Beckmann, E.; Burke, B. J.; Boyer, A.; Ayats, C.; Ley, S. V. Angew. Chem., Int. Ed. 2007, 46, 7633-7635.
10. Veitch, G. E.; Beckmann, E.; Burke, B. J.; Boyer, A.; Maslen, S. L.; Ley, S. V. Angew. Chem., Int. Ed. 2007, 46, 7629-7632.
11. Following our recent disclosure (see ref 2), it is now available via both total synthesis (see ref 10) and by degradation of the natural product (see ref 9).
12. Brougham, P.; Cooper, M. S.; Cummerson, D. A.; Heaney, H.; Thompson, N. Synthesis 1987, 1015-1017.
13. Straightforward increase of the reaction time from 7 to 10 d, under identical conditions (cf. ref 10), led to improved conversion in the epoxidation of 1. At this time, no further optimization has been performed for the epoxidation of 23-epi-1.
14. Denholm, A. A.; Jennens, L.; Ley, S. V.; Wood, A. Tetrahedron 1995, 57, 6591-6604.
15. Kraus, W.; Bokel, M.; Klenk, A.; Pohni, H. Tetrahedron Lett. 1985, 26, 6435-6438.
16. The semisynthesis of 3 from azadirachtin has previously been reported; see: Ley, S. V.; Anderson, J. C.; Blaney, W. M.; Lidert, Z.; Morgan, E. D.; Robinson, N. G.; Simmonds, M. S. J. Tetrahedron Lett. 1988, 29, 5433-5436.
17. Sankaram, A. V. B.; Murthy, M. M.; Bhaskaraiah, K.; Subramany, A. M.; Sultana, N.; Sharma, H. C.; Leuschner, K.; Ramaprasad, G.; Sitaramaiah, S.; Rukmini, C.; Rao, P. U. Natural Pesticides from the Neem Tree and Other Tropical Plants. In Proc. 3rd Int. Neem Conf. Schmutterer, H., Ascher, K. R. S., Eds.; Nairobi, Kenya, 1986.
18. Although we have reported the conversion of 6 to an epimeric mixture of 3 and 7 previously (see ref 9), 7 was not separated for full characterization.
19. Ley, S. V.; Anderson, J. C.; Blaney, W. M.; Jones, P. S.; Lidert, Z.; Morgan, E. D.; Robinson, N. G.; Santafianos, D.; Simmonds, M. S. J.; Toogood, P. L. Tetrahedron 1989, 45, 5175-5192.
20. Kumar, C. S. S. R.; Srinivas, M.: Yakkundi, S. Phytochemistry 1996, 45, 451-455.
21. 3, which was not observed for the natural product. This, combined with the significant difference between NMR spectra, has led us to conclude that the two compounds are different.
22. The synthesis of this compound has been reported in error, and we would like to thank the reviewer for pointing out this misprint; see: Ley, S. V.; Denholm, A. A.; Wood, A. Nat. Prod. Rep. 1993, 10, 109-157. In this reference, the compounds 52/53 depicted on p 117 should be the corresponding C-11 hemiacetals.
23. Although selective C-11 methylation of azadirachtin (6) can be achieved, attempts to then induce skeletal rearrangement led to decomposition. In the case of l-tigloyl-3-acetylazadirachtinin (9), it was not possible to effect C-11 methylation.
24. Kraus, W.; Bokel, M.; Schwinger, M.; Vogler, B.; Soellner, R.; Wendisch, D.; Steffens, R.; Wachendorff, U. Phytochemistry and Agriculture; Oxford University Press: Oxford, 1993.
25. It is worthy of note that 14 has been prepared previously from azadirachtin; see: Butterworth, J. H.; Percy, G. R.; Morgan, E. D. J. Chem. Soc, Perkin Trans. 1972, 1, 2445-2450.
26. Yamasaki, R. B.; Klocke, J. A. J. Agrie Food Chem. 1987, 35, 467-471.
27. We are confident that these compounds are correctly assigned as natural products and are not artifacts of isolation since treatment of azadirachtin with methanol under the isolation conditions (see ref 8) gave no trace of either 3 or 7. Similarly, 9 showed no conversion to 10 under the isolation conditions; see ref 8.