Total synthesis of nigellicine and nigeglanine hydrobromide

Organic Letters

Volumn 7, Issue 12, 2005, Pages 2449-2451

  Elliott, Eric L ^a   Bushell, Simon M ^a   Cavero, Marta ^a   Tolan, Brian ^a   Kelly, T Ross ^a  

^a BOSTON COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID DERIVATIVE; BROMINE DERIVATIVE; ISATIN DERIVATIVE; NIGEGLANINE HYDROBROMIDE; NIGELLICINE HYDROBROMIDE; PYRIDAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ACYLATION; AMINATION; ARTICLE; LITHIATION; SYNTHESIS;

ALKALOIDS; HETEROCYCLIC COMPOUNDS, 3-RING; INDAZOLES; MOLECULAR STRUCTURE; NIGELLA;

EID: 20544475280     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol050769m     Document Type: Article

References (24)

1. Chugai Pharmaceutical Co., Ltd., Japan, Japanese Patent 60004185, 1985; Chem. Abstr. 1985, 102, 220870.
2. Atta-ur-Rahman; Malik, S.; He, C.; Clardy, J. Tetrahedron Lett. 1985, 26, 2759-2762.
3. Liu, Y.; Yang, J.; Liu, Q. Chem. Pharm. Bull. 2004, 52, 454-455.
4. Atta-ur-Rahman; Malik, S.; Hasan, S. S.; Choudhary, M. I.; Ni, C. Z.; Clardy, J. Tetrahedron Lett. 1995, 36, 1993-1996.
5. A SciFinder Scholar search leads to a Ph.D. thesis titled "The Total Synthesis of Three Natural Products: Nigellicine, Nigellidine, and Chilenone-A" (Guneratne, R. D., Cornell University, 1988), but the title is misleading since the thesis does not describe the synthesis of 1 nor 3.
6. For the synthesis of some monocyclic analogues of nigellicine, see: Schmidt, A.; Habeck, T.; Kindermann, M. K.; Nieger, M. J. Org. Chem. 2003, 68, 5977-5982.
7. For a recent review see: Whisler, M. C.; MacNeil, S.; Snieckus, V.; Beak, P. Angew. Chem., Int. Ed. 2004, 43, 2206-2225.
8. (a) Akita, H.; Matsukura, H.; Oishi, T. Tetrahedron Lett. 1986, 27, 5397-5400.
9. (b) Claudi F.; Giorgioni, J. G.; Di Stefano, A.; Abbracchio, M. P.; Paoletti, A. M.; Balduinio. W. J. Med. Chem. 1992, 35, 4408-4414.
10. (c) Saari, W. S. (Merck), U.S. Patent 3671636, 1972; Chem. Abstr. 1972, 77, 88083.
11. Regiochemistry confirmed by nOe difference spectra (see Supporting Information).
12. (a) Carpino, L. A. J. Am. Chem. Soc. 1960, 82, 3133-3135.
13. (b) Ragnarsson, U. Chem. Soc. Rev. 2001, 30, 205-213.
14. Coleman, G. H. Org. Synth. 1964, 1, 442-445.
15. (a) Snyder, H. R.; Thompson, C. B.; Hinman, R. L. J. Am. Chem. Soc. 1952, 74, 2009-2012.
16. (b) Buu-Hoi, N. P.; Hoeffinger, J. P.; Jacquignon, P. J. Heterocycl. Chem. 1964, 1, 239-241.
17. Shen, Y.; Friestad, G. K. J. Org. Chem. 2002, 67, 6236-6239.
18. Regiochemistry confirmed by 1D-NOESY (see Supporting Information).
19. Some differences were noted between the IR spectrum of synthetic 1 and the IR of the natural product. An authentic sample of natural 1 was not available. See the Supporting Information for a tabulated comparison of the spectra of synthetic 1 and the natural material.
20. For examples of the thermal decarboxylation of indazole-3-carboxylic acids see: (a) Behr, L. C.; Fusco, R.; Jarboe, C. H. In Pyrazoles, Pyrazolines, Pyrazolidines, Indazoles, and Condensed Rings; Wiley, R. H., Ed.; Chemistry of Heterocyclic Compounds, Vol. 22; Wiley: New York, 1967.
21. (b) Borsche, W.; Diacont, K. Justus Liebigs Ann. Chem. 1934, 510, 287-296.
22. (c) von Auwers, K. Chem. Ber. 1922, 55, 1141-1157.
23. Unreacted starting material is recovered upon heating under neutral conditions up to 200°C in a variety of solvents, at which point nonproductive decomposition occurs. Heating in 1 M HCl, on the other hand, yields unreacted starting material up to 150°C, at which point nonproductive decomposition occurs.
24. 2O. Despite that compelling congruence, the IR and UV-vis spectra of synthetic 2 are different (see the Supporting Information) from those reported for the natural material. Unfortunately, we have been unable to obtain an authentic sample of the natural material or spectra thereof, despite repeated acknowledged requests.