A 环氧化调节笼状藤黄素的化学和生物活性。
A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones.
机构信息
Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA.
出版信息
Org Biomol Chem. 2013 May 28;11(20):3341-8. doi: 10.1039/c3ob40395e.
Abstract
Natural products of the caged Garcinia xanthones (CGX) family are characterized by a unique chemical structure, potent bioactivities and promising pharmacological profiles. We have developed a Claisen/Diels-Alder reaction cascade that, in combination with a Pd(0)-catalyzed reverse prenylation, provides rapid and efficient access to the CGX pharmacophore, represented by the structure of cluvenone. To further explore this pharmacophore, we have synthesized various A-ring oxygenated analogues of cluvenone and have evaluated their bioactivities in terms of growth inhibition, mitochondrial fragmentation, induction of mitochondrial-dependent cell death and Hsp90 client inhibition. We found that installation of an oxygen functionality at various positions of the A-ring influences significantly both the site-selectivity of the Claisen/Diels-Alder reaction and the bioactivity of these compounds, due to remote electronic effects.
摘要
笼状藤黄烷酮（CGX）家族的天然产物具有独特的化学结构、强大的生物活性和有前景的药理学特性。我们开发了一种克莱森/狄尔斯-阿尔德反应级联反应，与钯（0）催化的反向烯丙基化反应相结合，为 CGX 药效团提供了快速高效的途径，以克吕酮的结构为代表。为了进一步探索这个药效团，我们合成了各种 A 环氧化的克吕酮类似物，并评估了它们在生长抑制、线粒体碎片化、诱导线粒体依赖性细胞死亡和热休克蛋白 90 客户抑制方面的生物活性。我们发现，在 A 环的不同位置引入含氧官能团，由于远程电子效应，会显著影响克莱森/狄尔斯-阿尔德反应的位点选择性和这些化合物的生物活性。
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