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

说明(申请人提供)：含氮天然产物含有大量生物活性分子，常用作治疗疾病的有效药物。其中，羽扇豆胶生物碱具有良好的生物活性，表现出抗肝毒性和镇痛作用。此外，这些生物碱呈现出一个耐人寻味的结构结构，其特征是具有密集的官能化螺旋桨烷核。由于它们的生物学和结构特征，它们是整个合成努力的一个有吸引力的目标。拟议研究的目标是完成两个羽扇豆碱生物碱A和B的全合成。我们合成策略的关键是开发亲核剂与从手性助剂衍生的喹亚胺的非对映选择性的1，2-加成反应。由此产生的氨基二烯酮产品有望成为制备更复杂的螺旋烷生物碱的通用构件。通过采用统一的合成策略，可以很容易地制备出各种羽扇豆类生物碱及其衍生物。通过人工合成获得这些生物碱，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、更有效的天然产品。

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.