Total Synthesis of the Proposed Azaspiracid-1 Structure, Part 1: Construction of the Enantiomerically Pure C1–C20, C21–C27, and C28–C40 Fragments†
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 authorYiwei Li
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 authorNoriaki Uesaka 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 authorTheocharis V. Koftis 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 authorStepan Vyskocil 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 authorTaotao Ling 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 authorMugesh Govindasamy 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 authorWenyuan Qian 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 authorFederico Bernal
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 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 authorYiwei Li
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 authorNoriaki Uesaka 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 authorTheocharis V. Koftis 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 authorStepan Vyskocil 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 authorTaotao Ling 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 authorMugesh Govindasamy 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 authorWenyuan Qian 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 authorFederico Bernal
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 authorWe thank Dr. D. H. Huang and Dr. G. Siuzdak for NMR spectroscopic and mass spectrometric assistance, respectively, and Dr. Raj Chadha for X-ray crystallographic analysis. Financial support for this work was provided by the National Institutes of Health (USA) and The Skaggs Institute for Chemical Biology, predoctoral fellowships from Bristol-Myers Squibb (to F.B.), The Skaggs Institute for Research (to Y.L. and F.B.), The Scripps Research Institute Society of Fellows (to F.B.), and Eli Lilly (to Y.L.), and a postdoctoral fellowship from The Skaggs Institute for Research (to W.Q.).
Graphical Abstract
Als Bausteine für die Synthese einer postulierten Struktur von Azaspiracid-1 wurden beide Enantiomere der Teilstrukturen 2, 3 und 4 stereoselektiv hergestellt. Piv=Pivaloyl, PFP=Pentafluorphenyl, Teoc=2-(Trimethylsilyl)ethoxycarbonyl, TES=Triethylsilyl.
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