Vinylogous Amide Photochemistry in Organic Synthesis

有机合成中的乙烯酰胺光化学

• 批准号: 6734223
• 负责人: JEFFREY D WINKLER
• 金额: $ 21.16万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6734223
• 关键词: antineoplastics; chemical addition; chemical synthesis; cyclic ketone; cyclization; imides; indoles; marine toxins; neurotransmitter antagonist; photochemistry; stereochemistry

DESCRIPTION (provided by applicant): This proposal is directed towards the development of new methodology for the stereoselective construction of complex polycyclic ring systems and the application of this methodology to the synthesis of structures of biological significance. We describe herein the extension of the intramolecular vinylogous amide photocycloaddition/retro-Mannich/Mannich sequence that we have developed for the synthesis of perhydroindoles to the synthesis of bridged tricyclic aminoketones via intramolecular photocycloaddition of vinylogous imides. The development of the asymmetric variant of the photocycloaddition reaction will be examined, in the context of syntheses of three different naturally occurring compounds containing the azabicyclo[ 3.2.1]octane moiety: 1) peduncularine 1, from the genus Aristotelia, which displays activity against human breast cancer cells, 2) securinine 2, which is a specific GABA receptor antagonist, and 3) sarain A 3, a marine alkaloid with antitumor, antibacterial, and insecticidal activity produced by the sponge Reniera sarai.

描述（由申请人提供）：本提案旨在开发立体选择性构建复杂多环体系的新方法，并将该方法应用于合成具有生物学意义的结构。我们在本文中描述了我们已经开发的用于合成全氢吲哚的分子内乙烯基双酰胺光环加成/逆曼尼希/曼尼希序列的扩展，以通过乙烯基双酰亚胺的分子内光环加成来合成桥接的三环氨基酮。在合成三种不同的含有氮杂双环[ 3.2.1]辛烷部分的天然存在的化合物的背景下，将检查光环化加成反应的不对称变体的发展：1）peduncularine 1，来自苦碟子属，其显示出抗人乳腺癌细胞的活性，2）securinine 2，其是特异性GABA受体拮抗剂，和3）sarain A3，一种具有抗肿瘤、抗菌和杀虫活性的海洋生物碱，由海绵Reniera萨莱产生。