Total Synthesis of Bielschowskysin

Bielschowskysin 的全合成

• 批准号: 7168422
• 负责人: ADAM Kenneth CHARNLEY
• 金额: $ 4.6万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-23 至 2008-01-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7168422
• 关键词: Antimalarials; Architecture; Biological Factors; Biological Testing; Cyclization; Development; Diterpenes; Ethers; Ethyl Ether; Exhibits; Facility Construction Funding Category; In Vitro; Reporting; Skeleton; Structure; Structure-Activity Relationship; System; analog; anticancer activity; bielschowskysin; chemical synthesis; coral; cycloaddition; cytotoxicity; enol; fascinate; interest; novel; stereochemistry; tetradecane

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.

2004年初，从柳珊瑚中分离出高度功能化的二萜类化合物bielschowskysin 据报道，在NCI的体外细胞毒性中， 抗肿瘤筛选以及有效的抗疟疾活性。结构上，三环[9，3，0，0]十四烷骨架 代表了独特的二萜结构。前所未有的结构， Bielschowskysin与有效的抗癌和抗疟疾活性相结合，使这种二萜成为一种高度 化学合成的有吸引力的目标。重点的合成策略包括建设三环 通过在分子内光化学[2+2]中使用环状甲硅烷基烯醇醚的核环体系 环加成和分子内Nozaki-Hiyama-Kishi环化，以构建 比尔朔夫斯基辛。成功的全合成将建立绝对构型， 为生物学测试提供额外的材料，并允许获得类似物和中间体， 从天然材料中获得，以评估这种迷人的生物活性物质的构效关系 天然产物