Paulus Fritz, Heusel Corinna, Jaspers Marc, Amrehn Lilli M, Schreiner Florian, Rana Debanjan, Daniliuc Constantin G, Hansen Michael Ryan, Glorius Frank
Organisch-Chemisches Institut, University of Münster, Corrensstraße 36, 48149, Münster, Germany.
Institut für Physikalische Chemie, University of Münster, Corrensstraße 28/30, 48149, Münster, Germany.
Angew Chem Int Ed Engl. 2025 Jul;64(27):e202504793. doi: 10.1002/anie.202504793. Epub 2025 May 19.
closo-Carboranes are icosahedral carbon-boron clusters with unique properties and broad applicability. They particularly stand out in the context of drug development as privileged structural motifs for boron neutron capture therapy (BNCT) and as highly hydrophobic bioisosteres for the rotational volume of phenyl rings. Herein, we unveil the synthesis of N-protected carboranyl analogs of β-arylethylamines-widely found structural motifs in biologically active molecules-via a one-step alkene difunctionalization approach. Key for our success were the enabling mechanistic characteristics of energy transfer catalysis which we have used for the first time to generate closo-carboranyl radicals. Downstream modifications gave a series of analogs of amino acids and known N-methyl-d-aspartate receptor (NMDAR) antagonists.
闭式碳硼烷是具有独特性质和广泛适用性的二十面体碳硼簇。在药物开发领域,它们作为硼中子俘获疗法(BNCT)的优势结构基序以及苯环旋转体积的高疏水性生物电子等排体尤为突出。在此,我们通过一步烯烃双官能化方法揭示了β-芳基乙胺的N-保护碳硼烷基类似物的合成,β-芳基乙胺是生物活性分子中广泛存在的结构基序。我们成功的关键在于能量转移催化的有利机理特性,我们首次利用该特性生成闭式碳硼烷基自由基。后续修饰得到了一系列氨基酸类似物和已知的N-甲基-D-天冬氨酸受体(NMDAR)拮抗剂。