Enantioselective Synthesis of Manzamine A

描述（由申请人提供）：该项目需要开发一种双曼尼希级联方法来合成曼扎明生物碱。曼扎胺具有独特的结构，在其他天然产物中没有发现，并且它们具有显著的生物活性。特别是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，因此为了进一步研究其生物活性，必须开发一种有效的全合成方法。自1986年从海绵中分离出Manzamine A以来，仅进行了2次全合成。这个具有挑战性的分子的支架是通过建议跨环双曼尼希级联接近。这一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化合物。提出的有效和收敛的策略将提供一个新的接入点，这个有价值的家庭的天然产物。

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.