Enantioselective Synthesis of Manzamine A

曼扎明 A 的对映选择性合成

• 批准号: 6949709
• 负责人: JASON A MULDER
• 金额: $ 4.4万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-02 至 2006-08-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949709
• 关键词: alkaloids; amines; antimalarial agents; antineoplastics; biotherapeutic agent; chemical synthesis; drug design /synthesis /production; postdoctoral investigator

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.

描述（由申请人提供）：该项目需要开发曼尼奇级联的方法来合成Manzamine生物碱。 Manzamine具有独特的结构，在其他天然产品中没有发现，并且具有值得注意的生物学活性。曼氮胺A特别是具有明显的抗肿瘤和抗疟疾活性。它的天然来源是有限的，因此，为了进一步探索Manzamine A的生物学活性，必须开发出一种有效的总合成方法。自1986年与海洋海绵隔离以来，曼氮胺A A隔离为2个总合成。通过拟议的跨性别双曼尼奇级联反应，该具有挑战性的分子的脚手架可以接近。该策略将应用于曼氮胺A的对映选择性总合成，并适用于曼氮杂家族中的其他人。提出的高效和收敛策略将为这一宝贵的天然产品家族提供一个新颖的访问点。