The Second Total Synthesis of Diazonamide A†
K. C. Nicolaou Prof. Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorParaselli Bheema Rao Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorJunliang Hao Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorMali Venkat Reddy Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorGerasimos Rassias Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorXianhai Huang Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorDavid Y.-K. Chen Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorScott A. Snyder
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorK. C. Nicolaou Prof. Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorParaselli Bheema Rao Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorJunliang Hao Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorMali Venkat Reddy Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorGerasimos Rassias Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorXianhai Huang Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorDavid Y.-K. Chen Dr.
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorScott A. Snyder
Department of Chemistry and, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA, Fax: (+1) 858-784-2469
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
Search for more papers by this authorWe thank Dr. D. H. Huang and Dr. G. Siuzdak for NMR spectroscopic and mass spectrometric assistance, respectively. Financial support for this work was provided by The Skaggs Institute for Chemical Biology, American Biosciences, the National Institutes of Health (USA), predoctoral fellowships from the National Science Foundation and Pfizer (S.A.S.), and a postdoctoral fellowship from The Skaggs Institute for Chemical Biology (X.H.).
Graphical Abstract
Die hoch gespannte einzigartige Molekülstruktur und die potenzielle tumortherapeutische Wirkung von Diazonamid A (1) machen diesen Naturstoff zu einem attraktiven Syntheseziel. Zu den Schlüsselschritten dieser Totalsynthese von 1 zählen die neuartige SmI2-gestützte Ringöffnungs-Sequenz und die ungewöhnliche Oxidation eines Indolins zu einem Oxindol in Gegenwart von Pd(OH)2/C.
References
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- 30Selected data for compound 22: Rf=0.35 (EtOAc/hexanes=5:1); [α]
(CH3OH, c=0.69)=−277.25; IR (film): 
max=3260, 2919, 1713, 1660, 1602, 1496, 1443, 1401, 1302, 1261, 1214, 1155, 1055, 750 cm−1; 1H NMR (600 MHz, CD3CN): δ=10.38 (s, 1 H), 8.42 (s, 1 H), 7.54 (d, J=7.9 Hz, 1 H), 7.42–7.33 (m, 7 H), 7.27 (br m, 1 H), 7.22 (d, J=7.0 Hz, 1 H), 7.10 (d, J=7.4 Hz, 1 H), 6.89–6.87 (m, 2 H), 6.82 (t, J=7.9 Hz, 1 H), 6.77 (d, J=7.9 Hz, 1 H), 6.73 (s, 1 H), 6.15 (d, J=7.9 Hz, 1 H), 5.08 (AB quart, J=12.7 Hz, 
AB=17.1 Hz, 2 H), 4.55 (t, J=7.4 Hz, 1 H), 4.24 (ddd, J=11.4, 8.8, 3.1 Hz, 1 H), 3.23 (t, J=12.7 Hz, 1 H), 2.68 (d, J=11.4 Hz, 1 H), 2.00 (m, 1 H), 1.01 (d, J=6.1 Hz, 3 H), 0.91 ppm (d, J=6.1 Hz, 3 H); 13C NMR (150 MHz, CDCl3): δ=174.9, 173.8, 164.3, 156.3, 154.6, 152.9, 152.8, 143.2, 140.6, 138.0, 135.9, 134.5, 131.6, 130.6, 130.0, 129.4, 129.3, 128.8, 128.6, 128.2, 127.2, 126.9, 124.8, 124.5, 123.2, 122.7, 116.6, 112.4, 98.3, 67.0, 57.8, 57.0, 56.4, 37.8, 31.0, 19.6, 19.0 ppm; HRMS (MALDI): calcd for C43H32Cl2N6O7+: 815.1782 [M+H+], found: 815.1778.
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