Photoinduced Electron Transfer Processes for the Synthesis of Enantiopure Alkaloids

通过光诱导电子转移(PET)方法合成具有代表性的次生植物代谢物家族吡咯利齐啶、吲哚和喹啉的非对映和对映体选择性合成是此次德国/法国联合拨款申请的重点。我们计划通过改变环-环的核心结构以及通过取代基的变化，为设计具有高区域和非对映选择性的直接PET诱导的环化反应的光活性和电活性底物制定最佳策略。手性天然分子池中的底物被包括在逆合成中，以便获得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。以马来酰亚胺和琥珀酰亚胺引发的多羟基吡咯烷为目标分子，由吡啶盐引发的多羟基吲哚氮类化合物为目标分子。另一方面，我们计划优化PET敏化过程，通过激发电子受体对胺的单电子氧化和手性烯烃的额外自由基加成来产生自由基阳离子。这些反应的立体化学是完全可控的，特别是当涉及到胺上的手性中心时。为了获得立体选择过程的信息，扩大反应的范围，将研究胺和受体烯烃的结构变化。在某些情况下，需要修改反应条件以提高反应性(例如，许多无环叔胺的活性低于环状类似物)。不饱和叔胺的自由基串联反应也将以同样的方式进行研究。可获得各种含氮杂环，如吡咯里齐啶、吲哚咪啶或四氢异喹啉。其中许多化合物具有有趣的生物活性(例如，作为神经递质类似物)，并对其活性进行了测试。

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.