Photocatalyzed Decarboxylative B–C Couplings for the Synthesis of Carboranyl Amino Acids and Peptides

作者：Zhenghong Zhou, Han Ma, Jie Zhou, Yang Sun, Rongfeng Wu, Sen Gao, Shiyin Zhao, Bing Liu, Yong Nian, Bo Yang, Lijuan Zhu, Feng Zhu · 发表于：Journal of the American Chemical Society · 年份：2025 · DOI：10.1021/jacs.5c10308 · 被引用次数：13 · 研究领域：Boron Compounds in Chemistry、Radiopharmaceutical Chemistry and Applications、Organoboron and organosilicon chemistry

Boron neutron capture therapy (BNCT) is a promising and selective strategy for treating aggressive and refractory tumors, but its clinical success depends on the development of effective boron delivery agents. These agents must offer high tumor selectivity, structural stability, and sufficient boron content─criteria that current clinical options fail to fully satisfy. Herein, we report a visible-light-driven decarboxylative B-C cross-coupling between boron-functionalized carborane carboxylic acids and dehydroalanine (Dha)-containing peptides, enabling the first synthesis of boron-vertex-substituted carboranyl peptides under mild conditions. This photocatalyzed site-selective Giese involves the reaction of photogenerated boron vertex-centered carboranyl radicals to Dha residues, affording carborane-peptide conjugates in good to high yields and with excellent functional group tolerance. Enantiopure boron-vertex-substituted carboranylalanines were successfully synthesized using chiral Karady-Beckwith Dha derivatives, enabling their incorporation into well-defined complex peptides (comprising 5 and 15 residues) via solid-phase peptide synthesis. The synthetic utility of this platform was further demonstrated through a DNA-compatible click reaction, which enabled the attachment of carborane-bearing motifs to DNA tags. Moreover, B-C coupled carboranylalanines were conjugated to biologically relevant molecules such as nucleic acid aptamers to enhance tumor-targeting properties. Prel...