Total Synthesis of the Antitumor Agent Asparagamine A

该研究的目的是开发抗肿瘤生物碱天冬酰胺A的对映选择性合成，该生物碱已被证明对多种肿瘤细胞系具有体外抗肿瘤活性。MacMillan最近开发了第一个有机催化的吡咯与α，β-不饱和醛的不对称Michael加成反应。本文提出了一种新的延伸，以允许在催化循环中干预亚胺鎓离子中间体的氮杂-Prins环化。这将允许一步合成天冬酰胺胺A和stemofoline（一种相关生物碱）共有的核心桥接吡咯烷结构。所提出的合成方法既新颖又简洁。 此外，所提出的路线将允许构建可能具有显著药用价值的天然产物的类似物。

The goal of the proposed research is to develop an enantioselective synthesis of the antitumor alkaloid asparagamine A, which has been shown to have antitumor activity in vitro against a variety of tumor cell lines. MacMillan has recently developed the first organocatalytic, asymmetric Michael additions of pyrroles with alpha, beta- unsaturated aldehydes. Proposed herein is a novel extension to allow for the intervention of an aza-Prins cyclization of an iminium ion intermediate in the catalytic cycle. This will allow for a one-step synthesis of the core bridged pyrrolidine structure common to asparagamine A and stemofoline, a related alkaloid. The proposed synthesis is both novel and concise. Moreover, the proposed route will allow for the construction of analogs of the natural product that could be of significant medicinal value.