Total Synthesis of Phorboxazole B


  • The NIH (grants CA108488 and CA74394) graciously funded this research. We thank M. Dodge, L. Wysocki, J. Schuster, L. Boyle, L. Luther, and L. Konkel for providing starting materials crucial to this work. We are grateful to Dr. I. Guzei for the X-ray crystal structure determination of 19. Professors C. J. Forsyth (University of Minnesota) and D. R. Williams (Indiana University) are acknowledged for helpful discussions regarding the hydrolysis of 39.


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Challenge met: In the synthesis of phorboxazole B, a highly efficient hetero-Diels–Alder reaction was used to construct the key C33–C39 linchpin, allowing for the completion of the C18–C46 fragment (see picture). Coupling with a suitable C3–C17 partner was followed by late-stage formation of the oxazole unit, macrocyclization, and deprotection to afford synthetic phorboxazole B.