NMR Strategy for Unraveling Structures of Bioactive Sponge-Derived Oxy-polyhalogenated Diphenyl Ethers

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• 作者：Laurent Calcul ; Raymond Chow ; Allen G. Oliver ; Karen Tenney ; Kimberly N. White ; Alexander W. Wood ; Catherine Fiorilla ; Phillip Crews
• 刊名：Journal of Natural Products
• 出版年：2009
• 出版时间：March 27, 2009
• 年：2009
• 卷：72
• 期：3
• 页码：443-449
• 全文大小：193K
• 年卷期：v.72,no.3(March 27, 2009)
• ISSN：1520-6025

文摘

The overexpression of the Mcl-1 protein in cancerous cells results in the sequestering of Bak, a key component in the regulation of normal cell apoptosis. Our investigation of the ability of marine-derived small-molecule natural products to inhibit this protein−protein interaction led to the isolation of several bioactive oxy-polyhalogenated diphenyl ethers. A semipure extract, previously obtained from Dysidea (Lamellodysidea) herbacea and preserved in our repository, along with an untouched Dysidea granulosa marine sponge afforded 13 distinct oxy-polyhalogenated diphenyl ethers. Among these isolates were four new compounds, 5, 6, 10, and 12. The structure elucidation of these molecules was complicated by the plethora of structural variants that exist in the literature. During dereplication, we established a systematic method for analyzing this class of compounds. The strategy is governed by trends in the ¹H and ¹³C NMR shifts of the aromatic rings, and the success of the strategy was checked by X-ray crystal structure analysis.