Vinylogous Amide Photochemistry in Organic Synthesis

描述(申请人提供)：本提案旨在开发立体选择性构建复杂的多环环体系的新方法，并将该方法应用于合成具有生物学意义的结构。本文将我们开发的用于合成全氢吲哚的分子内乙烯基酰胺光环加成/逆向Mannich/Mannich序列扩展到通过乙烯基酰亚胺分子内光环加成合成桥联三环氨基酮。光环加成反应的不对称变体将在合成三种不同的自然存在的化合物的背景下进行研究，这些化合物包含氮杂双环[3.2.1]辛烷部分：1)马兜铃碱1，它具有抗人类乳腺癌细胞的活性；2)一叶菜碱2，它是一种特定的GABA受体拮抗剂；以及3)沙拉宁A3，一种由海绵Reniera Sarai产生的具有抗肿瘤、抗细菌和杀虫活性的海洋生物碱。

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.