Total Synthesis of Bielschowskysin

2004年初，从柳珊瑚中分离到了高度功能化的二萜bielschowsky sin Passopterogorgia Kolos，据报道在NCI的体外表现出强烈和特异的细胞毒性 抗肿瘤筛选以及强大的抗疟疾活性。从结构上看，三环[9，3，0，0]十四烷骨架 代表了一种独特的二萜结构。史无前例的结构 Belschowsky sin与强大的抗癌和抗疟疾活性相结合，使这种二萜成为一种高度 化学合成的诱人靶标。合成战略的亮点包括建造三环 环硅烯醇醚在分子内光化学中的应用[2+2] 环加成反应和分子内Nozaki-Hiyama-Kishi环合反应，构建了九元环 比尔肖夫斯基。Bielschowsky sin的成功全合成将建立绝对构型， 为生物测试提供额外的材料，并允许接触到类似物和中间体，而不是很容易 可从天然材料中获得，以评估这种迷人的生物活性的构效关系 天然产物。

The highly functionalized diterpene bielschowskysin was isolated in early 2004 from the gorgonian coral Pseudopterogorgia kallos and is reported to exhibit strong and specific in vitro cytotoxicity in the NCI's antitumor screen as well as potent antimalarial activity. Structurally, the tricyclo[9,3,0,0]tetradecane skeleton of bielschowskysin represents a unique diterpene architecture. The unprecedented structure of bielschowskysin combined with the potent anticancer and antimalarial activity makes this diterpene a highly attractive target for chemical synthesis. Highlights of the synthetic strategy include construction the tricyclic core ring system through the use of a cyclic silyl enol ether in an intramolecular photochemical [2+2] cycloaddition, and an intramolecular Nozaki-Hiyama-Kishi cyclization to construct the nine-membered ring of bielschowskysin. Successful total synthesis of bielschowskysin will establish the absolute configuration, provide additional material for biological testing, and allow access to analogs and intermediates, not readily available from the natural material, to evaluate the structure activity relationship of this fascinating bioactive natural product.