Total Synthesis of Spirastrellolide F Methyl Ester—Part 2: Macrocyclization and Completion of the Synthesis†
Stefan Benson Dipl.-Chem.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorMarie-Pierre Collin Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorGregory W. O'Neil Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorJulien Ceccon Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorBernhard Fasching Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorMichaël D. B. Fenster Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorCédrickx Godbout Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorKarin Radkowski
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorRichard Goddard Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorAlois Fürstner Prof.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorStefan Benson Dipl.-Chem.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorMarie-Pierre Collin Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorGregory W. O'Neil Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorJulien Ceccon Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorBernhard Fasching Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorMichaël D. B. Fenster Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorCédrickx Godbout Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorKarin Radkowski
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorRichard Goddard Dr.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorAlois Fürstner Prof.
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany), Fax: (+49) 208-306-2994
Search for more papers by this authorGenerous financial support by the MPG, the Chemical Genomics Center (CGC) of the MPG, the Fonds der Chemischen Industrie (Kekulé-stipend to S.B.), the Alexander-von-Humboldt Foundation (fellowships to G.O’N. and M.D.B.F.), the Fonds de Recherche sur la Nature et les Technologies Québec (fellowship to C.G.), and F. Hoffmann–La Roche, Basel, is gratefully acknowledged. We sincerely thank the NMR, X-ray, and chromatography departments of our Institute for excellent support over the entire duration of this project, the ANKA Angstroemquelle, Karlsruhe, for the provision of beamtime, and Prof. R. J. Andersen, University of British Columbia, Vancouver, for an exchange of information.
Graphical Abstract
Marvel of the sea: A concise and highly convergent total synthesis of the methyl ester of the marine macrolide spirastrellolide F (see picture), which has exquisite antimitotic properties, is reported. In this approach, the northern and the southern hemispheres of this intricate target are stitched together in only two consecutive steps (Suzuki coupling, Yamaguchi lactonization) without any interim protecting-group manipulations.
Supporting Information
Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors.
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- 23In our previous study, we have described a donor analogous to 18 protected by a TBS group. It was found, however, that this particular silyl group cleaves much slower than the secondary TBS groups at O9 and O1 as well as the isopropylidene acetal. Prolonged stirring of the material with PPTS, however, leads to partial decomposition of the final product. Therefore, the donor fragment 18 was prepared, which carries a more labile TES group as shown in Scheme 3. Furthermore, attempted coupling with the analogous donor featuring a free hydroxy group, as used by Paterson et al.,[6] did not work well in our hands.
- 24For details and a comprehensive data set, see the Supporting Information.
- 25It is of note that the NMR spectrum of synthetic spirastrellolide A methyl ester reported by Paterson and coworkers is identical to that of an authentic sample recorded under the same conditions on the same spectrometer,[6] but is distinctly different from the spectrum depicted in the Supporting Information of the isolation paper.[1]
