Synthesis and Evaluation of Modifications to the 6,7,6-fused Ring Depsidone Core

John Treadwell Terrell


Depsidones are 6,7,6-fused tricyclic natural products with a wide range of antibacterial activity (MIC = 0.0825-8 ppm). The Spiromastix sp. fungus, which was recently discovered in the deep sea near Japan, has been found to produce 15 new depsidone molecules known collectively as Spiromastixones A-O. This work involves the synthesis of B ring analogs with varying size and electronic profiles, and their effects on depsidones antibiotic activity. The core depsidone structure has been successfully synthesized, albeit with low yields, using a 4 step synthetic sequence involving copper catalyzed etherification and then esterification for ring closure. Modifications to this structure are currently underway to exchange the ester for both an amide and a thioester, as well as increasing the size of the central ring. Once synthesized, each depsidone analog will be evaluated for antibiotic activity against both Gram-positive and Gram-negative bacteria. The assays are expected to show how changes to the central ring affect biological activity. Modifications to the ester and ether functional groups are targeted for their electronic interactions with the active site for the molecule, whereas lengthening carbon chains of the starting materials will enlarge the central ring and show whether changing the size of the molecule strongly affects its activity.


Synthesis; Spiromastixones; Modification

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