2005年9月15日
P-43 インターロイキン-1β変換酵素阻害剤EI-1941-1,EI-1941-2およびEI-1941-3の不斉全合成と構造活性相関研究(ポスター発表の部)
天然有機化合物討論会講演要旨集
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- 巻
- 号
- 47
- 開始ページ
- 361
- 終了ページ
- 366
- 記述言語
- 日本語
- 掲載種別
- DOI
- 10.24496/tennenyuki.47.0_361
- 出版者・発行元
- 天然有機化合物討論会
The first asymmetric total synthesis of EI-1941-1 (1), -2 (2) and -3 (3), inhibitors of interleukin-1β converting enzyme (ICE), has been accomplished, starting from a chiral epoxy iodoenone 10, a key intermediate in our total synthesis of epoxyquinols A and B. In spite of the failure of the synthesis by our postulated biosynthetic route, they were diastereoselectively synthesized via an intramolecular carboxypalladation in a 6-endo cyclization mode, followed by β-hydride elimination, as the key steps. Hg(OTf)_2 afforded a carboxymercurated product of a side-chain relative stereochemistry opposite to that of the natural product, leading eventually to epi-EI-1941-2 with high diastereoselectivity. EI-1941-1 was synthesized stereoselectively from the intermediate of EI-1941-2, while EI-1941-3 was synthesized in one step from EI-1941-2. By this asymmetric total synthesis, the absolute stereochemistry of EI-1941-3 was determined. The structure-activity relationship of EI-1941-1, -2, -3, and their synthetic derivatives revealed that an enantiomer of EI-1491-2 is a more potent ICE inhibitor than EI-1491-2 with less cytotoxicity.
- リンク情報
- ID情報
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- DOI : 10.24496/tennenyuki.47.0_361
- CiNii Articles ID : 110006682572
- CiNii Books ID : AN00154136