Asymmetric Synthesis of Bioactive Natural Products Using Nazarov Cyclization

利用纳扎罗夫环化不对称合成生物活性天然产物

• 批准号: 7936513
• 负责人: Alison J Frontier
• 金额: $ 20.69万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7936513
• 关键词: 1,3-Butadiene; Aromatic Compounds; Attention; Behavior; Biological; Biological Factors; Carbamates; Chemicals; Complex; Cyclization; Development; Disease; Distant; Goals; Indium; Ketones; Lipoxygenase; Medical; Methods; Molecular Conformation; Neurodegenerative Disorders; Pattern; Positioning Attribute; Public Health; Reaction; Research; Research Personnel; Structure; System; Technology; Transition Elements; catalyst; combat; diketone; frontier; improved; interest; merrilactone A; novel; novel strategies; promoter; tetrapetalone A; tool

DESCRIPTION (provided by applicant): The proposed research will seek to 1) develop a general method to perform catalytic asymmetric Nazarov cyclization and 2) achieve the total synthesis of two natural products, merrilactone A and tetrapetalone A using Nazarov cyclization as the key step. These natural products are neurotrophic and inhibit lipoxygenases, respectively. Synthesis of these structurally interesting compounds will allow us to explore unique chemical transformations and improve our ability to study the bioactivity of these molecules. The research will contribute potentially enantioselective strategies for the synthesis of these and other natural products with biologically significant behavior, enabling chemists to prepare and study pharmacological agents for medical applications. As an example of potential impact of these chemical methods, one specific aim of this application describes the synthesis of the neurotrophic agent merrilactone A. The ability to synthesize a molecule of this complexity and unusual bioactivity could eventually provide medical researchers with tools to combat neurodegenerative diseases, and methods to synthesize other molecules that will impact diseases important to public health.

描述（由申请人提供）：拟议的研究将寻求1）开发一种进行催化不对称的纳扎罗夫环化学的通用方法，2）实现两种天然产品Merrilactone A和Tetrapetalone A的总合成，并使用Nazarov Cyclization作为关键步骤。这些天然产物分别是神经营养性的，分别抑制脂氧酶。这些结构上有趣的化合物的合成将使我们能够探索独特的化学转化并提高研究这些分子的生物活性的能力。这项研究将为具有生物学意义的行为综合这些和其他天然产品的合成潜在的对映选择性策略，从而使化学家能够为医疗应用准备和研究药理学剂。作为这些化学方法的潜在影响的一个例子，该应用的一个具体目的描述了神经营养剂梅拉酮的合成A.能够合成这种复杂性和异常生物活性分子的能力，最终可以为医学研究人员提供工具，以使神经退行性疾病的疾病和合成其他分类的方法对其他疾病进行对抗。