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: 8516064
• 负责人: Raul Navarro
• 金额: $ 1.93万
• 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 2013-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8516064
• 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.

描述（由申请人提供）：含氮天然产物包含大量生物活性分子，通常用作治疗疾病的有效药物。其中，hasubanan生物碱具有很好的生物活性，表现出抗肝毒性和镇痛特性。此外，这些生物碱提出了一个有趣的结构架构，其特征在于一个密集的功能化螺桨烷核心。由于它们的生物学和结构特征，hasubanans是全合成努力的有吸引力的目标。 本研究的目标是完成两个hasubanan生物碱成员periglaucines A和B的全合成。我们的合成策略的关键是开发一个非对映选择性的1，2-加成的亲核试剂的醌亚胺衍生的手性助剂。由此产生的氨基二烯酮产物有望在制备更复杂的螺桨烷生物碱中用作多功能的结构单元。通过采用统一的合成策略，有望容易地制备出多种哈苏巴南生物碱及其衍生物。通过合成这些生物碱，将有可能促进旨在阐明其生物学途径的研究，并有可能开发出新的、更有效的天然产物。

项目成果

Rapid construction of the aza-propellane core of acutumine via a photochemical [2 + 2] cycloaddition reaction.

• DOI: 10.1021/ol3017963
• 发表时间: 2012-09-07
• 期刊: ORGANIC LETTERS
• 影响因子: 5.2
• 作者: Navarro, Raul;Reisman, Sarah E.
• 通讯作者: Reisman, Sarah E.