Li Yu, Cheng Shihao, Tian Yun, Zhang Yanan, Zhao Yu
School of Pharmacy, Nantong University, Nantong 226001, China.
Nat Prod Rep. 2022 Oct 19;39(10):1970-1992. doi: 10.1039/d2np00027j.
Covering: 2013-2022.Chemical diversification of natural products is an efficient way to generate natural product-like compounds for modern drug discovery programs. Utilizing ring-distortion reactions for diversifying natural products would directly alter the core ring systems of small molecules and lead to the production of structurally complex and diverse compounds for high-throughput screening. We review the ring distortion reactions recently used in complexity-to-diversity (CtD) and pseudo natural products (pseudo-NPs) strategies for diversifying complex natural products. The core ring structures of natural products are altered ring expansion, ring cleavage, ring edge-fusion, ring spiro-fusion, ring rearrangement, and ring contraction. These reactions can rapidly provide natural product-like collections with properties suitable for a wide variety of biological and medicinal applications. The challenges and limitations of current ring distortion reactions are critically assessed, and avenues for future improvements of this rapidly expanding field are discussed. We also provide a toolbox for chemists for the application of ring distortion reactions to access natural product-like molecules.
2013年至2022年。天然产物的化学多样化是为现代药物发现计划生成类天然产物化合物的有效方法。利用环畸变反应使天然产物多样化将直接改变小分子的核心环系统，并导致产生结构复杂多样的化合物用于高通量筛选。我们综述了最近在复杂性到多样性（CtD）和伪天然产物（pseudo-NPs）策略中用于使复杂天然产物多样化的环畸变反应。天然产物的核心环结构通过环扩展、环裂解、环边缘融合、环螺环融合、环重排和环收缩而改变。这些反应可以迅速提供具有适合各种生物学和医学应用性质的类天然产物库。对当前环畸变反应的挑战和局限性进行了批判性评估，并讨论了这一快速发展领域未来改进的途径。我们还为化学家提供了一个工具箱，用于应用环畸变反应来获得类天然产物分子。
