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Total Synthesis of Beauvericin Using Dehydroamino Acid Residues to Facilitate Cyclization

  • Author(s): Cizio, Gregory Thomas
  • Advisor(s): Dong, Vy M
  • et al.
Abstract

A unique strategy that helps facilitate macrocyclization has been developed and utilized in the synthesis of a cyclic hexadepsipeptide natural product. By using dehydrophenylalanine amino acids in the synthesis of beauvericin, the precursor to the macrocycle is folded in such a way that the C- and the N- termini of the depsipeptide are closer together and cyclization is facilitated. Two strategies towards construction of the macrocycle have been investigated: (1) a cyclotrimerization approach which utilizes a monomeric dipeptide oxazolone and (2) a linear approach which cyclizes a hexadepsipeptide oxazolone. The macrocycle then underwent a global N-methylation followed by rhodium-catalyzed asymmetric hydrogenation which reduced the unsaturated amino acid residues to their desired saturated forms to give rise to the natural product. With the cyclotrimerization route, beauvericin was afforded in 10% yield over 8 steps, and with the linear route, beauvericin was afforded in 19% yield over 12 steps.

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