Concise Total Synthesis of (+)-Croomine

( )-Croomine 的简明全合成

• 批准号: 6551093
• 负责人: TEHSHIK P YOON
• 金额: $ 3.66万
• 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/6551093
• 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).

性状（由申请方提供）：Croomine是百部生物碱类的代表性成员。这些新的多环天然产物是从东亚传统医学中广泛使用的药用植物中分离出来的，作为止咳和抗结核药物。除了它们的药用用途之外，百部生物碱最近因其有效的杀虫活性而引起关注。值得注意的是，这类天然产物的大多数成员的结构特征在于共同的吡咯烷基丁内酯核。已经提出了一种通过催化乙烯基曼尼希反应来获得这种结构基序的对映选择性方法。这项研究计划依赖于Jacobsen最近开发的Strecker反应非金属催化剂的能力，以激活亚胺的亲核攻击。预计将富电子的2-甲硅烷基氧呋喃添加到亚胺催化剂复合物中将具有高水平的对映体和非对映体选择性。用于该转化的催化剂结构的优化将通过催化剂类似物的小的“集中”库的组合合成来进行。在探索了这种新反应的底物范围后，将在（+）-色罗明的简明全合成（7步，最佳情况）中证明对映选择性乙烯基Mannich的合成效用。