In Situ Generation of Fluorescent Amino Acids and Peptides via Double C–H Activation/Annulation
In Situ Generation of Fluorescent Amino Acids and Peptides via Double C–H Activation/Annulation
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DOI：
10.1021/acscatal.3c03783
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发表时间：
2023-10
期刊：
影响因子：
12.9
通讯作者：
Liangliang Song;Zhefan Zhang;Zhenwei Lv;Jinyuan Xu;Mengru Zhan;Shuo Tang;Huanhuan Li;Nanxi Wang;Lingchao Cai
中科院分区：
文献类型：
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作者：
Liangliang Song;Zhefan Zhang;Zhenwei Lv;Jinyuan Xu;Mengru Zhan;Shuo Tang;Huanhuan Li;Nanxi Wang;Lingchao Cai
为了获得更好的发射波长、荧光寿命和量子产率，人们已经合成了非天然的荧光氨基酸。尽管取得了重大进展，但它们中的大多数都面临着作为荧光团的固有限制，并且局限于氨基酸和荧光团之间的偶联方法。在本论文中，我们开发了一种Rh(III)催化的不同苯甲酰胺与炔烃的双C-H活化/环化反应，用于合成三环稠合芳烃正离子。这一策略的稳健性体现在基于赖氨酸的氨基酸和多肽的多样化上，原位生成三环荧光团。该方法具有底物范围广、原子和步骤经济性高、化学选择性和位置选择性高等特点。采用两种不同的炔烃进行不对称的双C-H活化/环化反应，可以高产率地合成非天然的荧光氨基酸。这些三环荧光团显示出可调的荧光发射，低的细胞毒性，以及特异性靶向溶酶体的潜力。
Unnatural fluorescent amino acids have been synthesized to obtain better emission wavelengths, fluorescence lifetime, and quantum yields. Despite major advances, most of them face inherent restrictions as fluorophores and are limited to the methods from coupling between amino acids and fluorophores. Herein, we develop a Rh(III)-catalyzed double C–H activation/annulation reaction of diverse benzamides with alkynes for the synthesis of tricyclic-fused aromatic hydrocarbon carbocations. The robustness of this strategy is demonstrated by the diversification of Lys-based amino acids and peptides, in situ generating tricyclic fluorophores. This method features broad substrate scope and high atom and step economy as well as high chemo- and site selectivity. Unsymmetrical double C–H activation/annulation employing two different alkynes is well tolerated to produce the unnatural fluorescent amino acids in high yields. These tricyclic fluorophores display tunable fluorescence emission, low cytotoxicity, and the potential for specifically targeting lysosomes.