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。曼扎明具有其他天然产品中没有的独特结构，并且它们具有值得注意的生物活性。特别是甘草胺A，具有显著的抗肿瘤和抗疟疾活性。甘露糖胺A的天然来源有限，为了进一步研究其生物活性，必须建立一种有效的全合成方法。自1986年从一块海绵中分离出来以来，曼扎明A只有两次合成失败。这种具有挑战性的分子的支架是可以通过提议的跨环双曼尼奇级联来接近的。这一策略将应用于对映体选择性全合成甘露糖胺A，并将适用于甘露糖胺家族的其他化合物。拟议的高效和融合战略将为这一宝贵的天然产品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.