9 三次元構造多様性に富んだセスキテルペン類似低分子群の短段階合成と抗原虫感染症活性物質の探索(口頭発表の部)

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The inhibitors of Ca^<2+>-ATPases exemplified by artemisinin and transtaganolides possess highly oxygenated sesquiterpene frameworks. We focused our attention to the tricyclic system as a common structural motif of the Ca^<2+>-ATPase inhibitors aside from the differences in their stereochemical relationships of the ring junctions and oxygenated functionalities incorporated into the cyclic skeletons. To access varied molecular architectures related to the biologically active sesquiterpenes, we envisioned stereochemical diversification of the consecutive ring-junctions into three types involving trans-cis, cis-cis and trans-trans fused skeletons. Tandem ring-closing olefin metathesis reactions of three dienynes possessing distinct stereochemical relationships (anti-syn, syn-syn and anti-anti) would furnish the sets of tricyclic skeletons. With an aim of rapid and stereo-controlled assembly of dienynes into the three consecutive carbon centers on cyclohexane rings, six-membered oxonitrile 3 was designed as a versatile scaffold for installing the dienynes on the three sites (A-C). Based on this strategy, we have developed an expeditious and programmable synthetic process that controls not only the stereochemical relationships of ring-junctions but also the modes of cyclization, which entails formation of six types of the tricyclic skeletons in a systematic fashion. Furthermore, isomerization of internal dienes and subsequent photo-oxidation were demonstrated to construct a collection of artemisinin analogs and also increase three-dimensional structural diversity of the small molecule library. Preliminary results on the screening and SAR studies of anti-parasitic substances will be presented.
天然有機化合物討論会の論文
2008-09-01

9 三次元構造多様性に富んだセスキテルペン類似低分子群の短段階合成と抗原虫感染症活性物質の探索(口頭発表の部)

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