Chemistry and biology of diazonamide A: First total synthesis and confirmation of the true structure

Journal of the American Chemical Society

Volumn 126, Issue 40, 2004, Pages 12888-12896

  Nicolaou, K C ^a   Chen, David Y K ^a   Huang, Xianhai ^a   Ling, Taotao ^a   Bella, Marco ^a   Snyder, Scott A ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

BIOCHEMISTRY; MOLECULAR STRUCTURE; NITROGEN; OXYGEN; STEREOCHEMISTRY; SYNTHESIS (CHEMICAL);

DIAZONAMIDES; MOLECULAR PUZZLE; OXYGEN ATOMS;

AMINES;

AMIDE; DIAZONAMIDE A; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; CHIRALITY; REACTION ANALYSIS; STEREOCHEMISTRY; SYNTHESIS;

EID: 5644298630     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja040092i     Document Type: Article

References (49)

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3. In truth, only a few of the creative strategies developed toward the original structure managed to identify a sequence that could generate either of these 12-membered systems in any measurable yield. See, for example: (a) Nicolaou, K. C.; Snyder, S. A.; Simonsen, K. B.; Koumbis, A. E. Angew. Chem., Int. Ed. 2000, 39, 3473-3478.
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17. (b) Overman, L. E.; Paone, D. V.; Stearns, B. A. J. Am. Chem. Soc. 1999, 121, 7702-7703. Later, another group developed a biomimetic, three-step approach to the same target. Although it lacked any stereocontrol, it afforded the same product in 30% yield following separation from the undesired stereoisomers: Ishikawa, H.: Takayama, H.; Aimi, N. Tetrahedron Lett. 2002, 43, 5637-5639.
18. For the preliminary communication of this total synthesis, see Nicolaou, K. C.; Bella, M.; Chen. D. Y.-K.; Huang, X.; Ling, T.; Snyder, S. A. Angew. Chem., Int. Ed. 2002, 41, 3495-3499.
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40. Other examples of such selective cyclizations as dictated by the stereochemistry of the intervening chain exist. See, for example, one of the classic total syntheses of erythronolide: Woodward, R. B.; Logusch, E.; Nambiar, K. P.; Sakan, K.; Ward, D. E.; Au-Yueng, B.-W.; Balaram, P.; Browne, L. J.; Card, P. J.; Chen, C. H.; Chênevert, R. B.; Fliri, A.; Frobel, K.; Gais, H.-J.; Garratt, D. G.; Hayakawa, K.; Heggi, W.; Hesson, D. P.; Hoppe, D.; Hoppe, I.; Hyatt, J. A.; Ikeda, D.; Jacobi, P. A.; Kim, K. S.; Kobuke, Y.; Kojima, K.; Krowicki, K.; Lee, V. J.; Leutert, T.; Malchenko, S.; Martens, J.; Matthews, R. S.; Ong, B. S.; Press: J. B.; Rajan Babu, T. V.; Rosseau, G.; Sauter, H. M.; Suzuki, M.; Tatsuta, K.; Tolbert, L. M.; Truesdale, E. A.; Uchida, I.; Ueda, Y.; Uychara, T.; Vasella, A. T.; Vlauchick, W. C.; Wade, P. A.; Williams, R. M.; Wong, N.-C. J. Am. Chem. Soc. 1981, 103, 3213-3215.
41. While we would be unable to accomplish this closure through cationic chemistry, the anionic alternative does work (see ref 5).
42. Wipf, P.; Miller, C. P. J. Org. Chem. 1993, 58, 3604-3606.
43. A typical yield based on recovered starting material for this process was around 50%.
44. 3SnH-induced reaction while the bulk of the remaining material from the Witkop conditions remained unchanged from starting material, this observation lends further support that this particular macrocyclization reaction proceeds through a mechanism based on intramolecular photoinduced electron transfer from the D-ring indole chromophore to the adjacent benzenoid E-ring.
45. Neither of the conditions developed for our key reactions in our model studies proved directly applicable to fully functionalized intermediates. Although such outcomes often occur, its consistency throughout the diazonamide campaign is indicative of the severely compact nature of the target in which the alteration of a single group or the addition of a few atoms can instigate several new problems with established chemistry.
46. Lindquist, N.; Fenical, W.; Van Duyne, G. D.; Clardy, J. J. Am. Chem. Soc. 1991, 113, 2303-2304.
47. 4) which, in 1, coincided precisely with the reported value for the natural product (3.88 ppm), whereas in 53 this proton appeared at 3.92 ppm.
48. In line with expectations, synthetic diazonamide A (1) exhibited potent cytotoxic activity at single digit nM concentrations against a variety of human cancer cell lines of distinct origin, including ovarian carcinoma 1A9, lung carcinoma A549, prostate carcinoma PC-3, breast carcinoma MCS-7, and the Taxol-resistant 1A9/PTX10 cell line. We thank Dr. Paraskevi Giannakakou and Aurora O'Brate, Emory University Winship Cancer Center, for performing these studies. More detailed discussion and additional biological studies are described in the following article.28
49. Nicolaou, K. C.; Hao, J.; Reddy, M. V.; Bheema Rao, P.; Rassias, G.; Snyder, S. A.; Huang, X.; Chen, D. Y.-K.; Brenzovich, W. E.; Giuseppone, N.; Giannakakou, P.; O'Brate, A. J. Am. Chem. Soc, 2004, 126, XXXX-XXXX.