Total synthesis of (+)-cortistatin A

Angewandte Chemie - International Edition

Volumn 47, Issue 38, 2008, Pages 7310-7313

  Nicolaou, K C ^a,b,c   Sun, Ya Ping ^a   Peng, Xiao Shui ^a   Polet, Damien ^a   Chen, David Y K ^a  

^a INSTITUTE OF CHEMICAL AND ENGINEERING SCIENCES   (Singapore)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Antitumor agents; Cascade reactions; Natural products; Total synthesis

Indexed keywords

CHEMICAL REACTIONS; MARINE ENGINEERING; RAW MATERIALS;

ANTITUMOR AGENTS; CASCADE REACTIONS; NATURAL PRODUCTS; TOTAL SYNTHESIS;

SYNTHESIS (CHEMICAL);

ANGIOGENESIS INHIBITOR; CORTISTATIN A; ISOQUINOLINE DERIVATIVE; POLYCYCLIC HYDROCARBON;

ARTICLE; CHEMISTRY; SYNTHESIS;

ANGIOGENESIS INHIBITORS; ISOQUINOLINES; POLYCYCLIC COMPOUNDS;

EID: 53149089484     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200803550     Document Type: Article

References (27)

1. P. Carmeliet, Nature 2005, 438, 932-936.
2. S. Aoki, Y. Watanabe, M. Sanagawa, A. Setiawan, N. Kotoku, M. Kobayashi, J. Am. Chem. Soc. 2006, 128, 3148-3149.
3. Y. Watanabe, S. Aoki, D. Tanabe, A. Setiawan, M. Kobayashi, Tetrahedron 2007, 63, 4074-4079.
4. S. Aoki, Y. Watanabe, D. Tanabe, A. Setiawan, M. Arai, M. Kobayashi, Tetrahedron Lett. 2007, 48, 4485-4488.
5. For the first synthesis of cortistatin A, see: a) R. A. Shenvi, C. A. Guerrero, J. Shi, C.-C. Li, P. S. Baran, J. Am. Chem. Soc. 2008, 130, 7241-7243;
6. for studies toward the synthesis of cortistatins, see: b) S. Yamashita, K. Iso, M. Hirama, Org. Lett. 2008, DOI: 10.1021/o18012099;
7. c) E. M. Simmons, A. R. Hardin, X. Guo, R. Sarpong, Angew. Chem. 2008, DOI: 10.1002/anie.200802203;
8. Angew. Chem. Int. Ed. 2008, DOI: 10.1002/anie.200802203.
9. For a recent review on cascade reactions in total synthesis, see: K. C. Nicolaou, D. J. Edmonds, P. G. Bulger, Angew. Chem. 2006, 118, 7292-7344;
10. Angew. Chem. Int. Ed. 2006, 45, 7134-7186.
11. S. Kotha, K. Lahiri, D. Kashinath, Tetrahedron 2002, 58, 9633-9695.
12. K. Sonogashira, Handbook of Organopalladium Chemistry for Organic Synthesis, Vol. 1, Wiley-Interscience, New York, 2002, pp. 493-529.
13. Compound 8 was synthesized from the Hajos-Parrish ketone according to procedure described by Danishefsky and co-workers. For the synthesis of ent-8, see: R. C. A. Isaacs, M. J. Di Grandi, S. J. Danishefsky, J. Org. Chem. 1993, 58, 3938-3941.
14. For the preparation of the Hajos-Parrish ketone (94%ee, as determined by optical rotation), see: Organic Syntheses 1990, Coll. Vol. 7, 363-368.
15. J. R. Parikh, W. V. E. Doering, J. Am. Chem. Soc. 1967, 89, 5505-5507.
16. a) S. Ohira, Synth. Commun. 1989, 19, 561-564;
17. b) S. Müller, B. Liepold, G. J. Roth, H. J. Bestmann, Synlett 1996, 521-522;
18. c) G. J. Roth, B. Liepold, S. G. Müller, H. J. Bestmann, Synthesis 2004, 59-62.
19. K. C. Nicolaou, C. J. N. Mathison, T. Montagnon, J. Am. Chem. Soc. 2004, 126, 5192-5201.
20. 2], KOAc, bispinacolato diboron, DMSO, 80°C, 50%; for the preparation of 7-bromoisoquinoline, see: B. R. Miller, J. M. Frincke, J. Org. Chem. 1980, 45, 5312-5315.
21. Chemo- and stereoselective hydrogenation of the cyclopentenyl isoquinoline system was first demonstrated with model system 24, and confirmed by X-ray crystallographic analysis of the hydrogenated product 25. CCDC 684134 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. (Chemical Equation Presented) ORTEP drawing of 25 with thermal ellipsoids shown at the 50% probability level.
22. K. C. Nicolaou, D. L. F. Gray; T. Montagnon; S. T. Harrison, Angew. Chem. 2002, 114, 1038-1042;
23. T. Montagnon; S. T. Harrison, Angew. Chem. 2002, 114, 1038-1042;
24. Angew. Chem. Int. Ed. 2002, 41, 996-1000.
25. The chemo- and facial selectivity of 1,4-addition to simplified trienone system 26 was first demonstrated in a model study towards cortistatin J, where detailed NMR analysis of trienyl dimethylamine 29 revealed the 1,4-addition took place from the β face. (Chemical Equation Presented)
26. 13C NMR, and MS analysis. (Chemical Equation Presented)
27. For a structural-activity relationship study of naturally occurring cortistatins, see: S. Aoki, Y. Watanabe, D. Tanabe, M. Arai, H. Suna, K. Miyamoto, H. Tsujibo, K. Tsujikawa, H. Yamamoto, M. Kobayashi, Bioorg. Med. Chem. 2007, 15, 6758-6762.