Synthetic Studies Towards Periglaucines A, B, and Related Bioactive Hasubanans

Periglaucines A、B 和相关生物活性 Hasubanan 的合成研究

• 批准号: 8131386
• 负责人: Raul Navarro
• 金额: $ 4.18万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8131386
• 关键词: Alkaloids; Analgesics; Antiviral Agents; Architecture; Biological; Biological Factors; Biology; Chemistry; Complex; Development; Disease; Exhibits; Goals; Hepatitis B Virus; Imines; Lead; Methods; Mono-S; Nitrogen; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacologic Substance; Physical condensation; Preparation; Property; Quinones; Reaction; Reagent; Research; Source; Therapeutic Agents; chemical synthesis; ketal; member; novel; novel strategies

DESCRIPTION (provided by applicant): Nitrogen-bearing natural products comprise a large number of biologically active molecules, often serving as effective pharmaceuticals in the treatment of disease. Of these, the hasubanan alkaloids possess promising biological activity, exhibiting antihepatotoxic and analgesic properties. In addition, these alkaloids present an intriguing structural architecture characterized by a densely functionalized propellane core. As a result of their biological and structural features, the hasubanans are an attractive target for total synthetic endeavors. The goal of the proposed research is to complete the total synthesis of two members of the hasubanan alkaloids, periglaucines A and B. Key to our synthetic strategy is the development of a diastereoselective 1,2-addition of nucleophiles to quinone imines derived from a chiral auxiliary. The resulting aminodienone products are expected to serve as versatile building blocks in the preparation of more complex propellane alkaloids. By employing a unified synthetic strategy, it is expected that a variety hasubanan alkaloids and derivatives can be readily prepared. With synthetic access to such alkaloids, it will be possible to facilitate studies aimed at elucidating their biological pathways and to potentially develop novel, more potent natural products. PUBLIC HEALTH RELEVANCE: Natural products have long served as a rich source of pharmaceutical drugs utilized for the treatment of many diseases. Studies aimed at efficiently preparing such molecules ultimately helps facilitate their availability to patients worldwide. Additionally, this type of research can also lead to the discovery of novel, more potent pharmaceutical drugs.

描述（申请人提供）：含氮天然产物包含大量生物活性分子，通常作为治疗疾病的有效药物。其中，哈苏巴南生物碱具有良好的生物活性，具有抗肝毒性和镇痛特性。此外，这些生物碱呈现出一种有趣的结构体系，其特征是密集功能化的螺旋桨核心。由于其生物学和结构特征，哈苏巴南是全合成研究的一个有吸引力的目标。 本研究的目标是完成哈苏巴南生物碱两个成员 periglaucines A 和 B 的全合成。我们合成策略的关键是开发亲核试剂与源自手性醌亚胺的非对映选择性 1,2-加成反应。辅助的。所得的氨基二烯酮产品预计将作为制备更复杂的丙烷生物碱的通用结构单元。通过采用统一的合成策略，预计可以很容易地制备多种哈苏巴南生物碱和衍生物。通过合成这些生物碱，将有可能促进旨在阐明其生物途径的研究，并有可能开发出新颖、更有效的天然产品。 公共卫生相关性：天然产物长期以来一直是用于治疗许多疾病的药物的丰富来源。旨在有效制备此类分子的研究最终有助于促进它们为全世界患者所用。此外，此类研究还可以发现新的、更有效的药物。