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Stereoselective Total Synthesis of (−)-Spirofungin A by Utilising Hydrogen-Bond Controlled Spiroketalisation

Authors

  • John E. Lynch,

    1. School of Chemistry, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010 (Australia), Fax: (+61) 3-9347-8396
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  • Dr. Shannon D. Zanatta,

    1. School of Chemistry, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010 (Australia), Fax: (+61) 3-9347-8396
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  • Prof. Dr. Jonathan M. White,

    1. School of Chemistry, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010 (Australia), Fax: (+61) 3-9347-8396
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  • Prof. Dr. Mark A. Rizzacasa

    Corresponding author
    1. School of Chemistry, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010 (Australia), Fax: (+61) 3-9347-8396
    • School of Chemistry, The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, Victoria 3010 (Australia), Fax: (+61) 3-9347-8396
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Abstract

The stereoselective total synthesis of the spiroketal containing Streptomyces metabolite (−)-spirofungin A (1) is described. A key step involved a spiroketalisation controlled by an intramolecular H-bond which favoured the desired spiroketal 4 (13:1 ratio). The presence of the intramolecular H-bond in 4 is possibly due to a 1,5-alkyne–oxygen interaction. Other key steps include an efficient cross-metathesis to form the spiroketal precursor, a tin mediated syn-aldol reaction and a Stille cross-coupling reaction to create the C22[BOND]C23 bond. A final Wittig extension followed by deprotection gave (−)-spirofungin A (1).

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