Synthesis and Biological Properties of the Cytotoxic 14-Membered Macrolides Aspergillide A and B

Authors

  • Dr. Santiago Díaz-Oltra,

    1. Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Avda. Sos Baynat s/n, 12071 Castellón (Spain), Fax: (+34) 964728214
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  • César A. Angulo-Pachón,

    1. Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Avda. Sos Baynat s/n, 12071 Castellón (Spain), Fax: (+34) 964728214
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  • Dr. Juan Murga,

    1. Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Avda. Sos Baynat s/n, 12071 Castellón (Spain), Fax: (+34) 964728214
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  • Dr. Eva Falomir,

    1. Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Avda. Sos Baynat s/n, 12071 Castellón (Spain), Fax: (+34) 964728214
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  • Prof. Dr. Miguel Carda,

    Corresponding author
    1. Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Avda. Sos Baynat s/n, 12071 Castellón (Spain), Fax: (+34) 964728214
    • Depart. de Q. Inorgánica y Orgánica, Univ. Jaume I, Avda. Sos Baynat s/n, 12071 Castellón (Spain), Fax: (+34) 964728214
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  • Prof. Dr. J. Alberto Marco

    Corresponding author
    1. Depart. de Q. Orgánica, Univ. de Valencia, c/D. Moliner, 50, 46100 Burjassot, Valencia (Spain), Fax: (+34) 963544328
    • Depart. de Q. Orgánica, Univ. de Valencia, c/D. Moliner, 50, 46100 Burjassot, Valencia (Spain), Fax: (+34) 963544328
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Abstract

Total, stereoselective syntheses of the naturally occurring, cytotoxic macrolides aspergillide A and B are described. Olefin metatheses and asymmetric allylations were key steps in the synthetic sequences. Cytotoxicity assays against several tumor cell lines have been performed for the two aspergillides and some of the intermediates or side products of the synthetic sequence. One of these intermediates has been found markedly active against the human leukemia cancer cell line HL-60, with an IC50 value comparable with that of the clinical drug fludarabine.

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