Conformationally Restricted (+)-Cacospongionolide B Analogues. Influence on Secretory Phospholipase A2 Inhibition

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• 作者：Ryan P. Murelli ; Atwood K. Cheung ; Marc L. Snapper
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：March 2, 2007
• 年：2007
• 卷：72
• 期：5
• 页码：1545 - 1552
• 全文大小：209K
• 年卷期：v.72,no.5(March 2, 2007)
• ISSN：1520-6904

文摘

A new approach to (+)-cacospongionolide was developed to access conformationally restricted variantsof the natural product. The flexible aliphatic region between the decalin and side chain portion of thenatural product was replaced with alkenyl and alkynyl linkers to probe the influence of structural rigidityin the inhibition of secretary phospholipase A₂ (sPLA₂). It was found that when the aliphatic section isreplaced with a Z-olefin or an alkyne, sPLA₂ inhibitory activity suffered relative to the natural product;however, an E-olefin-containing analogue led to an enhanced activity. These results suggest that preferredsPLA₂ binding conformation of the natural product is similar to the geometry of the E-olefin-containinganalogue.