Development of Iridium-catalyzed, intramolecular, asymmetric allylic alkylation reactions and their application towards the total synthesis of Aquilarabietic Acid H

合成有机化学在药物发现和开发以及药物化学中仍然是最重要的。这导致近年来人们对催化、对映体选择性合成越来越感兴趣，特别是关于难以获得的四元立体中心。在前期研究的基础上，该研究项目将初步集中于发展一种Ir催化的、分子内不对称的1，3-二酮基烯丙基烷基化反应。这将允许容易地获得具有邻近的四元-三元立体中心的各种碳环。然后将这种新的方法应用于全合成青蒿酸H，这是一种在初步研究中显示出抗抑郁特性的新型天然化合物。此外，不对称的分子内反应随后将扩展到含有碳环的烯丙基的底物。这将使人们很容易获得类固醇和相关药物中常见的多环基序。

Synthetic organic chemistry continues to be of highest importance within drug discovery and development, as well as medicinal chemistry. This led to increased interest in catalytic, enantioselective synthesis in recent years, particularly regarding difficult to access, quaternary stereocenters. Based on previous initial studies the research project will initially focus on developing an Iridium-catalyzed, intramolecular, asymmetric allylic alkylation reaction of 1,3-dicarbonyls. This would allow easy access to various carbocycles with vicinal quaternary-tertiary stereocenters. This new methodology is then to be applied to the total synthesis of Aquilarabietic Acid H, a novel natural compound that showed anti-depressant properties in initial studies. Further, the asymmetric, intramolecular reaction is then to be extended to substrates with carbocycle-containing allyl moieties. This would give easy access to polycyclic motifs commonly found in steroids and related pharmaceutical drugs.