The goal of the proposed research is to develop an efficient asymmetric synthesis of salicylihalamide A, a novel antitumor agent. Salicylihalamide A has been shown to have extraordinary activity against a variety of human solid tumor cell lines (mean GI50 approximately 15 x 10-9 M in the National Cancer Institutes 60 tumor cell line panel). Intriguingly, salicylihalamide A did not exhibit any significant correlation to the profiles of known antitumor compounds in the National Cancer Institute's standard agent database. This suggests that salicylihalamide A may have a unique mechanism of cellular tumor inhibition. The potential for development of a new class of chemotherapeutic agents and the paucity of material available from the natural source make salicylihalamide A an attractive target for synthesis. The proposed synthesis will make available sufficient quantities of the natural product for biological testing.
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