Concise Total Synthesis of (+)-Croomine

( )-Croomine 的简明全合成

• 批准号: 6630423
• 负责人: TEHSHIK P YOON
• 金额: $ 4.16万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6630423
• 关键词: Diels Alder reaction; Schiff bases; acylation; alkaloids; alkylation; biological products; butyrolactone; catalyst; chemical addition; chemical structure; chemical synthesis; combinatorial chemistry; furans; high throughput technology; postdoctoral investigator; protonation; pyrrolidines; stereochemistry

DESCRIPTION (provided by applicant): Croomine is a representative member of the Stemona class of alkaloids. These novel polycyclic natural products were isolated from medicinal plants used extensively in traditional East Asian medicine as antitussive and antituburcular agents. In addition to their medicinal uses, the Stemona alkaloids have recently attracted attention for their potent insecticidal activity. Notably, the structures of most members of this class of natural products are characterized by a common pyrrolidinyl butyrolactone core. An enantioselective method of accessing this structural motif via a catalytic vinylogous Mannich reaction has been proposed. This research plan relies on the ability of Jacobsen's recently developed non-metal catalyst for the Strecker reaction to activate imines towards nucleophilic attack. The addition of electron-rich 2-silyloxyfurans to the imine-catalyst complex is expected to occur with high levels of enantio- and diastereoselectivity. Optimization of the catalyst structure for this transformation will be performed by combinatorial synthesis of a small, "focused" library of catalyst analogs. After exploring the substrate scope of this new reaction, the synthetic utility of the enantioselective vinylogous Mannich will be demonstrated in a concise total synthesis of (+)-croomine (7 steps, best case).

描述（由申请人提供）：Croomine是Stemona类生物碱类的代表成员。这些新型的多环天然产物是从传统东亚药物中广泛使用的抗毒性和抗胸腔剂中分离出来的。除了药物用途外，stemona生物碱最近还引起了其有效的杀虫活性的关注。值得注意的是，这类天然产物中大多​​数成员的结构的特征在于常见的吡咯烷丁酰基乳酸酯核心。已经提出了一种通过催化乙烯基曼尼克反应访问该结构基序的对映选择性方法。该研究计划依赖于雅各布最近开发的非金属催化剂来streck催化剂反应以激活亚胺向亲核攻击的能力。预计将添加富含电子的2-硅氧曲霉在亚胺催化剂复合物中以高水平的对映选择性和对映选择性发生。该转换的催化剂结构的优化将通过组合催化剂类似物的“聚焦”库的组合合成来进行。在探索了这种新反应的底物范围之后，将在简明的（+） - croomine（7个步骤，最佳情况）的简洁总合成中证明对映射乙烯基元素的合成效用。