Photoinduced Electron Transfer Processes for the Synthesis of Enantiopure Alkaloids

通过光诱导电子转移（PET）方法非对映体和对映体选择性合成次生植物代谢物家族吡咯烷、吲哚嗪和喹嗪的代表是德国/法国联合资助申请的重点。我们计划通过改变环化的核心结构以及取代基的变化来发展用于直接PET诱导的环化的具有高区域选择性和非对映选择性的光活性和电活性底物的设计的最佳策略。来自手性天然分子库的底物包括在逆合成中，以实现起始材料中已有的最大手性信息。计划研究介质效应，以找到电子转移步骤以及随后的C-C键形成步骤的最佳条件。作为靶分子，多羟基化吡咯烷由马来酰亚胺和琥珀酰亚胺引发，多羟基化吲哚嗪另外由吡啶鎓盐PET-光化学引发。另一方面，我们计划优化PET敏化过程，通过激发电子受体和额外的自由基加成到手性烯烃的胺的单电子氧化产生自由基阳离子。这些反应的立体化学是完全控制的，特别是当涉及胺上的手性中心时。为了获得立体选择过程的信息和扩大反应的范围，将研究胺和受体烯烃的结构的变化。在一些情况下，需要改变反应条件以增加反应性（例如，许多无环叔胺的反应性低于环状类似物）。不饱和叔胺的自由基串联反应将以同样的方式进行研究。可获得多种含氮杂环，例如吡咯烷、吲嗪或四氢异喹啉。其中许多具有有趣的生物活性（如神经递质类似物），衍生物的活性有待测试。

The diastereo- and enantioselective synthesis of representatives of the secondary plant metabolite families pyrrolizidines, indolizidines and quinolizidines by photoinduced electron transfer (PET) methods is in the focus of this german/french joint grant application. We plan to evolve optimal strategies for the design of photo- and electroactive substrates for direct PET-induced cyclizations with high regio- and diastereoselectivity by variation of the core structures for ring-annulation as well as by substituent variations. Substrates from the pool of chiral natural molecules are included in the retrosyntheses in order to achieve maximum chiral information already in the starting materials. Medium effects are planned to be studied in order to find optimal conditions for the electron transfer step as well as the subsequent C-C bond forming steps. As target molecules, polyhydroxylated pyrrolizidines are triggered from maleimides and succinimides, polyhydroxylated indolizidines additionally from pyridinium salt PET-photochemistry. On the other hand, we plan to optimize PET-sensitized processes that generate radical cations via single electron oxidation of amines by excited electron acceptors and additional radical addition to chiral alkenes. The stereochemistry of these reactions is to be entirely controlled especially as chiral centers on the amine are concerned. The variation of the structures of the amines and the acceptor olefin will be studied in order to get information on the stereoselection process and to enlarge the scope of the reaction. In several cases, the reaction conditions need to be modified to increase the reactivity (e.g. many acyclic tertiary amines are less reactive than cyclic analogues). Radical tandem reactions of unsaturated tertiary amines will be investigated in the same way. A variety of nitrogen containing heterocycles such as pyrrolizidines, indolizidines, or tetrahydroisoquinolines is available. Many of them possess interesting biological activity (e.g. as neurotransmitter analogues) and derivatives are to be tested on their activities.