Synthetic Studies in the Didemnin Series
Semi-synthetic studies directed toward didemnin analogues in which structural modifications were introduced in the side chain for investigating structure-activity relationships have been performed. The syntheses of several known didemnins including didemnin M, dehydrodidemnin B, and pyroglutamyl didemnin B have been successfully completed. In addition, several new didemnin analogues have been synthesized including glutaminyl didemnin B, (Ala$\sp3$) didemnin B, (Ala$\sp3$) didemnin M, and various other alaninyl derivatives. A total of forty didemnin analogues (thirty-four of which are new) were prepared semi-synthetically. In vitro cytotoxicity, antiviral activity, and structure-activity relationships for the above compounds are reported. Both glutaminyldidemnin B and (Ala$\sp3$) didemnin B show significantly greater activity against L1210 cells (murine leukemia) than the natural source of didemnin B.
University of Illinois - Urbana-Champaign
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University of Illinois at Urbana-Champaign