Enantioselective Synthesis of Manzamine A

描述（由申请人提供）：该项目需要开发双曼尼希级联方法来合成曼扎胺生物碱。锰胺具有其他天然产物所没有的独特结构，具有显著的生物活性。尤其是Manzamine A，具有显著的抗肿瘤和抗疟疾活性。由于其天然来源有限，为了进一步挖掘其生物活性，必须开发一种高效的全合成方法。Manzamine A自1986年从海绵中分离出来以来，只进行了2次全合成。这种具有挑战性的分子的支架可以通过拟议的跨环双曼尼希级联来接近。该策略将应用于曼扎明A的对映选择性全合成，并将适用于曼扎明家族的其他成员。所提出的高效和收敛的策略将为这一宝贵的天然产物家族提供一个新的接入点。

DESCRIPTION (provided by applicant): This project entails the development of a double mannich cascade approach to the synthesis of the manzamine alkaloids. The manzamines have a unique structure, not found in other natural products, and they possess noteworthy biological activity. Manzamine A, in particular, possesses significant antitumor and antimalarial activity. Its natural source is limited, so in order for the biological activity of manzamine A to be further explored, an efficient method for its total synthesis must be developed. Manzamine A has succumbed to only 2 total syntheses since its isolation in 1986 from a marine sponge. The scaffold of this challenging molecule is approachable via the proposed transannular double mannich cascade. This strategy will be applied toward the enantioselective total synthesis of manzamine A, and would be applicable to others in the manzamine family. The efficient and convergent strategy proposed would provide a novel access point to this valuable family of natural products.