Conformationally restricted (+)-cacospongionolide B analogues. Influence on secretory phospholipase A2 inhibition.
Conformationally restricted (+)-cacospongionolide B analogues. Influence on secretory phospholipase A2 inhibition.
复制标题
构象限制的 ( )-cacospongionolide B 类似物。
DOI：
10.1021/jo061407a
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Snapper,MarcL
中科院分区：
文献类型：
--
作者：
Murelli,RyanP;Cheung,AtwoodK;Snapper,MarcL
开发了一种新的方法来获得天然产物的构象受限变体。用烯基和炔基取代天然产物十氢萘和侧链之间的柔性脂肪区，探讨结构刚性对分泌型磷脂酶A2(SPLA2)抑制的影响。研究发现，当脂族部分被AZ-烯烃或炔烃取代时，sPLA2抑制活性相对于天然产物而言有所下降；而含有环烯烃类似物的sPLA2抑制活性则有所增强。这些结果表明，天然产物的PLA2结合构象类似于含电子烯烃类似物的几何构象。
A new approach to (+)-cacospongionolide was developed to access conformationally restricted variants of the natural product. The flexible aliphatic region between the decalin and side chain portion of the natural product was replaced with alkenyl and alkynyl linkers to probe the influence of structural rigidity in the inhibition of secretary phospholipase A2(sPLA2). It was found that when the aliphatic section is replaced with aZ-olefin or an alkyne,sPLA2inhibitory activity suffered relative to the natural product; however, anE-olefin-containing analogue led to an enhanced activity. These results suggest that preferredsPLA2binding conformation of the natural product is similar to the geometry of theE-olefin-containing analogue.