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

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作用。此外，这些生物碱呈现出一种有趣的结构结构，其特征是具有密集功能化的推进剂核心。由于其生物学和结构特征，hasubanans是全合成努力的一个有吸引力的目标。本研究的目标是完成hasubanan生物碱的两个成员，环环劳辛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-亲核试剂加入到从手性助剂衍生的醌亚胺中。所得到的胺二烯酮产品有望作为制备更复杂的推进剂生物碱的通用构件。通过采用统一的合成策略，期望可以很容易地制备各种hasubanan生物碱及其衍生物。有了这些生物碱的合成途径，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。

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.