Synthesis of Bioactive Natural Products

描述（由申请人提供）：该计划的目标是开发想法和反应序列，将简单的、商业上可用的化合物转化为结构复杂的、高效的、具有生物活性的天然产物，并研究这些物质在生物环境中的特性。本应用中描述的化学研究的基本主题是设计和执行级联反应，快速形成两种天然产物的拓扑和立体化学复杂结构：(1)有前途的血管生成抑制剂皮质抑素A，(2)强效和选择性抗癌化合物maoystal v。这些天然产物具有真正的潜力，作为治疗人类疾病的化疗药物和分子结构，激发了有机合成领域概念的发展。新的合成方案源于这样一种想法，即合理的基本羰基依赖性反应序列将使这些具有挑战性的目标分子能够快速合成。在这个项目中开发的合成途径将被用来深入了解这些迷人的天然产物的生物分子目标选择性。外行语言：用于治疗人类疾病的小分子药物和用于细胞生物学中基于发现的研究活动的分子探针都是通过化学合成的方法和概念生产的。该计划的意义在于，它将为实现两种结构复杂、具有生物活性的天然产物的短时间、高效合成和发现新的生物分子靶点来攻击人类疾病而开发强有力的思想和方法。公共卫生相关性：构思和发展强大的策略和反应序列，以迅速形成具有生物活性的天然产物的复杂分子结构，是化学合成领域的前沿活动之一。该项目正在开发创新的羰基级联环化，用于合成几种具有改善人类健康特性的天然产品。

DESCRIPTION (provided by applicant): The objectives of this proposed program are to develop ideas and reaction sequences to transform simple, commercially available compounds into structurally complex, biologically active natural products with high efficiency and to investigate the properties of these substances in biological contexts. The underlying theme of the chemical studies described in this application is the design and execution of cascades of reactions that rapidly form the topologically and stereochemically complex structures of two natural products: (1) the promising angiogenesis inhibitor Cortistatin A, and (2) the potent and selective anticancer compound Maoecrystal V. These natural products have genuine potential as chemotherapeutic agents for the treatment of human diseases and molecular architectures that inspire the development of concepts for the benefit of the field of organic synthesis. The new synthesis proposals are rooted in the idea that judicious sequences of fundamental, carbonyl-dependent reactions will enable rapid syntheses of these challenging target molecules. The synthesis pathways developed in this program will be leveraged to gain insights into the biomolecular target selectivities of these fascinating natural products. Lay language: Small molecule drugs for the treatment of human diseases and molecular probes for discovery-based research activities in cell biology are produced by the methods and concepts of chemical synthesis. The significance of this program comes from the powerful ideas and methods that it will develop for achieving short, efficient syntheses of two structurally complex, biologically active natural products and the discoveries of new biomolecular targets for attacking diseases in humans. PUBLIC HEALTH RELEVANCE: The conception and development of powerful strategies and reaction sequences to rapidly form the complex molecular structures of biologically active natural products is one of the frontier activities in the field of chemical synthesis. This program is developing innovative carbonyl-based cascades of cyclizations for use in syntheses of several natural products with properties that could improve human health.