Concise Total Synthesis of (+)-Croomine

描述(由申请人提供)：克罗明是Stemona类生物碱中具有代表性的成员。这些新的多环天然产物是从东亚传统医学中广泛用作镇咳和抗结核药物的药用植物中分离出来的。除了它们的药用用途外，百部生物碱最近因其强大的杀虫活性而引起了人们的注意。值得注意的是，这类天然产物的大多数成员的结构特征是一个共同的吡咯烷基丁内酯核心。本文提出了一种通过催化乙烯Mannich反应获得该结构基序的对映选择性方法。这项研究计划依赖于雅各布森最近开发的用于Strecker反应的非金属催化剂的能力，以激活亚胺进行亲核攻击。富含电子的2-硅氧基呋喃与亚胺-催化剂的加成反应有望以较高的对映体和非对映选择性进行。这一转化的催化剂结构的优化将通过组合合成一个小的、“重点”的催化剂类似物库来执行。在探索了这一新反应的底物范围后，将以(+)-克罗明的简明全合成(最好情况下为7步)来展示对映体选择性乙烯基曼尼希的合成用途。

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).