Total Synthesis of the Antitumor Agent Asparagamine A

抗肿瘤药物天冬酰胺A的全合成

• 批准号: 6522684
• 负责人: CHRISTOPHER J SINZ
• 金额: $ 3.39万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-04 至 2003-07-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6522684
• 关键词: alkaloids; antineoplastics; chemical addition; chemical synthesis; cyclization; drug design /synthesis /production; stereochemistry; stereoisomer

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.

该研究的目标是开发抗肿瘤生物碱天冬酰胺 A 的对映选择性合成方法，该化合物已被证明在体外对多种肿瘤细胞系具有抗肿瘤活性。 MacMillan 最近开发了第一个有机催化、吡咯与 α、β-不饱和醛的不对称迈克尔加成反应。本文提出了一种新颖的扩展，以允许在催化循环中干预亚胺离子中间体的氮杂-普林斯环化。这将允许一步合成天冬酰胺 A 和 Stefoline（一种相关生物碱）所共有的核心桥联吡咯烷结构。所提出的合成既新颖又简洁。 此外，所提出的路线将允许构建具有重要药用价值的天然产物的类似物。

项目成果

Total synthesis of diazonamide A.

• DOI: 10.1039/c0sc00577k
• 发表时间: 2011
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Knowles RR;Carpenter J;Blakey SB;Kayano A;Mangion IK;Sinz CJ;Macmillan DW
• 通讯作者: Macmillan DW