Total Synthesis of the Antitumor Agent Diazonamide A

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DESCRIPTION (provided by applicant): The objective of the proposed research is to develop an enantioselective total synthesis of diazonamide A. The natural product was isolated from the marine ascidian diazona chinensis, and possesses potent in vitro activity against HCT-116 human colon carcinoma and B-16 murine melanoma cancer cell lines with IC50 in the nanomolar range. The proposed research utilizes a novel organocatalysis strategy, developed in the MacMillan group, to generate the furolindoline core of diazonamide. Successful installation of the furolindoline core will serve as the platform for refining and developing new chemical methods to complete the bismacrocyclic framework of diazonamide A. An expeditious completion of the natural product will not only provide a synthetic sample, but also permits access to unnatural analogues for further biological evaluation.