Concise Asymmetric Total Synthesis of (+)-Peganumine A

( )-Peganumine A 的简明不对称全合成

• 批准号: 280719730
• 负责人: Dr. Marcel Weiss
• 金额: --
• 依托单位: Institut für Organische Chemie (IOC)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/280719730?language=en
• 关键词: Concise; Asymmetric; Total; Synthesis; Peganumine

Cancer is still one of the main causes of death in Germany, second only to diseases of the circulatory system. Thus the development of new drugs for cancer prevention and treatment is still a highly important task. Recently a complex beta-carboline alkaloid, (+)-peganumine A, with excellent potential application as an anticancer compound was isolated from the seeds of Peganum harmala. Its novel polycyclic scaffold presents a formidable synthetic challenge and offers significant opportunity for development of new and broadly applicable chemistry. Inspired by biosynthetic considerations an asymmetric total synthesis is planned that employs readily available starting materials. The key step in this concise synthesis is envisioned to be either an asymmetric Pictet-Spengler reaction or a selective coupling of beta-carboline derivatives. The investigation and development of efficient strategies for generation of the necessary two contiguous quaternary substituted carbon centers with stereochemical control will be explored using efficient strategies including catalytic asymmetric Pictet-Spengler reactions, readily available chiral auxiliaries and catalytic asymmetric Michael addition reactions. The synthetic samples of (+)-peganumine A and advanced synthetic intermediates accessed in these studies will be subject to detailed evaluation for anticancer activity through established collaborative engagements of the Movassaghi group at the MIT Koch Institute for Integrative Cancer Research.

在德国，癌症仍然是导致死亡的主要原因之一，仅次于循环系统疾病。因此，开发预防和治疗癌症的新药仍然是一项非常重要的任务。近年来，从马鞭草种子中分离到一种具有良好抗癌潜力的复合-碳碱生物碱(+)-马鞭草碱a。它的新型多环支架提出了一个巨大的合成挑战，并为新的和广泛应用的化学的发展提供了重要的机会。受生物合成考虑的启发，计划采用现成的起始材料进行不对称全合成。在这个简洁的合成的关键步骤被设想是一个不对称的picet - spengler反应或选择性偶联的-羰基衍生物。本研究将探讨利用催化不对称Pictet-Spengler反应、易获得的手性助剂和催化不对称Michael加成反应等有效策略，在立体化学控制下生成必要的两个连续的四元取代碳中心的有效策略。在这些研究中获得的(+)-peganumine A的合成样品和高级合成中间体将通过麻省理工学院科赫综合癌症研究所Movassaghi小组建立的合作协议进行详细的抗癌活性评估。