A NOVEL CASCADE APPROACH TO THE ASPIDOSPERMA ALKALOIDS

一种新颖的级联方法研究无冬子生物碱

• 批准号: 6208528
• 负责人: GRIER A WALLACE
• 金额: $ 3.09万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-10 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6208528
• 关键词: Diels Alder reaction; aspidosperma alkaloid; biological products; chemical synthesis; molecular rearrangement; stereochemistry

The aspidosperma alkaloids are an ever-growing class of indole alkaloids which posses complex architectures and a wide array of biological activity. For example, vincristine and vinblastine have long been used as cancer therapeutics. The following research proposal describes a novel cascade approach to these alkaloids. Through the coupling of an intramolecular Diels-Alder cyclization with an amino-Cope rearrangement we hope to set the four contiguous stereocenters in the aspidosperma alkaloids during a single synthetic step. This approach has the potential to be the shortest synthesis of these alkaloids to date. In addition, it should be readily adaptable to the synthesis many of the aspidosperma alkaloids. Through the development of this new methodology we hope to further our understanding of both the intramolecular Diels-Alder cyclization and the amino-Cope rearrangement, two very powerful synthetic transformations.

蜘蛛生物碱是一类不断增长的吲哚生物碱，具有复杂的结构和广泛的生物活性。 例如，长春新碱和长春花碱长期以来一直被用作癌症治疗剂。 以下研究计划描述了这些生物碱的新颖级联方法。 通过分子内 Diels-Alder 环化与氨基-Cope 重排的偶联，我们希望在单个合成步骤中在蜘蛛生物碱中设置四个连续的立体中心。 这种方法有可能成为迄今为止这些生物碱的最短合成方法。 此外，它应该很容易适应许多蜘蛛植物生物碱的合成。 通过开发这种新方法，我们希望进一步了解分子内 Diels-Alder 环化和氨基-Cope 重排这两种非常强大的合成转化。